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Clinical Trial Results:
A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed, refractory hematologic malignancies

Summary
EudraCT number	2013-000445-39
Trial protocol	GB ES
Global end of trial date	30 Apr 2020

Results information
Results version number	v1(current)
This version publication date	12 May 2021
First version publication date	12 May 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

116183

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Oct 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Apr 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

PART 1: To determine the safety, tolerability and maximum tolerated dose (MTD), following once daily (QD) and/or twice daily (BID) dosing schedules, establishing the recommended Phase 2 dose (RP2D) of GSK525762 in adult subjects with acute leukemia (AML), multiple myeloma (MM), or non-Hodgkin’s lymphoma (NHL). PART 2: To evaluate clinical efficacy after treatment with GSK525762 in AML. To evaluate clinical efficacy after treatment with GSK525762 in MM. To evaluate clinical efficacy after treatment with GSK525762 in NHL.

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

14 May 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Spain: 22

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Korea, Republic of: 8

Country: Number of subjects enrolled

United States: 42

Worldwide total number of subjects

111

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was an open-label repeat dose, multicenter study to investigate the safety, pharmacokinetics (PK), pharmacodynamics and clinical activity of GSK525762 in participants with relapsed, refractory hematologic malignancies. The study was conducted in 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion)

Screening details

A total of 111 participants were enrolled (87 participants in Part 1 and 24 participants in Part 2) across the study centers in Australia, Spain, Great Britain, South Korea and United State of America (USA).

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1: GSK525762 5 mg QD

Arm description

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 10 mg QD

Arm description

Participants were administered once daily oral dose of 10 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 20 mg QD

Arm description

Participants were administered once daily oral dose of 20 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 30 mg QD MM

Arm description

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 40 mg QD

Arm description

Participants were administered once daily oral dose of 40 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 40 mg QD MM

Arm description

Participants with MM were administered once daily oral dose of 40 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 60 mg QD AML

Arm description

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 60 mg QD NHL

Arm description

Participants with Non-Hodgkin’s Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 60 mg QD MM

Arm description

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 75 mg QD AML

Arm description

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 80 mg QD

Arm description

Participants were administered once daily oral dose of 80 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 80 mg QD AML

Arm description

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 80 mg QD NHL

Arm description

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 100 mg QD AML

Arm description

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 1: GSK525762 120 mg QD AML

Arm description

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 2: GSK525762 60 mg QD CTCL

Arm description

Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 2: GSK525762 75 mg QD MDS

Arm description

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Part 2: GSK525762 80 mg QD CTCL

Arm description

Participants CTCL were administered once daily oral dose of 80 mg GSK525762

Arm type

Experimental

Investigational medicinal product name

GSK525762

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received an oral dose of GSK525762 once daily.

Number of subjects in period 1	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Started	1	1	1	5	1	4	8	18	3	8	1	7	7	16	6	7	16	1
Completed	1	1	1	4	0	4	7	16	2	8	1	7	7	15	6	1	13	0
Not completed	0	0	0	1	1	0	1	2	1	0	0	0	0	1	0	6	3	1
Consent withdrawn by subject	-	-	-	1	-	-	1	1	1	-	-	-	-	-	-	2	-	-
Other Study closed/terminated	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	4	3	1
Lost to follow-up	-	-	-	-	1	-	-	1	-	-	-	-	-	-	-	-	-	-
Investigator discretion	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-

Baseline characteristics

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Reporting group title

Part 1: GSK525762 5 mg QD

Reporting group description

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

Reporting group title

Part 1: GSK525762 10 mg QD

Reporting group description

Participants were administered once daily oral dose of 10 mg GSK525762.

Reporting group title

Part 1: GSK525762 20 mg QD

Reporting group description

Participants were administered once daily oral dose of 20 mg GSK525762.

Reporting group title

Part 1: GSK525762 30 mg QD MM

Reporting group description

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

Reporting group title

Part 1: GSK525762 40 mg QD

Reporting group description

Participants were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

Part 1: GSK525762 40 mg QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD AML

Reporting group description

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD NHL

Reporting group description

Participants with Non-Hodgkin’s Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 75 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD

Reporting group description

Participants were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD NHL

Reporting group description

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 100 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

Reporting group title

Part 1: GSK525762 120 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

Reporting group title

Part 2: GSK525762 60 mg QD CTCL

Reporting group description

Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 2: GSK525762 75 mg QD MDS

Reporting group description

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

Part 2: GSK525762 80 mg QD CTCL

Reporting group description

Participants CTCL were administered once daily oral dose of 80 mg GSK525762

Reporting group values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL	Total
Number of subjects	1	1	1	5	1	4	8	18	3	8	1	7	7	16	6	7	16	1	111
Age categorical
Units: Subjects
18-64 years	1	0	0	4	0	3	3	11	3	3	0	3	4	7	4	4	1	0	51
65-74 years	0	1	0	0	1	0	5	5	0	3	0	2	3	3	1	2	9	1	36
>74 years	0	0	1	1	0	1	0	2	0	2	1	2	0	6	1	1	6	0	24
Sex: Female, Male
Units: Participants
Female	0	0	0	2	0	2	1	5	1	7	0	4	2	6	1	5	6	0	42
Male	0	0	0	3	0	2	7	13	2	1	0	3	5	10	5	2	10	0	63
Data not reported due to confidentiality/ privacy	1	1	1	0	1	0	0	0	0	0	1	0	0	0	0	0	0	1	6
Race/Ethnicity, Customized
Units: Subjects
Japanese (H)/eastAsian(H)/Southeast Asian(H)	0	0	0	2	0	0	0	5	1	0	0	0	1	1	0	1	0	0	11
Black or African american	0	0	0	0	0	0	0	1	1	0	0	2	0	0	0	0	1	0	5
Native hawaiian or other pacific islander	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
White	0	0	0	3	0	4	6	12	1	8	0	5	5	14	6	5	15	0	84
Asian & native hawaiian/other pacific islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Missing	0	0	0	0	0	0	2	0	0	0	0	0	0	1	0	1	0	0	4
Data not reported due to confidentiality/ privacy	1	1	1	0	1	0	0	0	0	0	1	0	0	0	0	0	0	1	6

End points

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Reporting group title

Part 1: GSK525762 5 mg QD

Reporting group description

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

Reporting group title

Part 1: GSK525762 10 mg QD

Reporting group description

Participants were administered once daily oral dose of 10 mg GSK525762.

Reporting group title

Part 1: GSK525762 20 mg QD

Reporting group description

Participants were administered once daily oral dose of 20 mg GSK525762.

Reporting group title

Part 1: GSK525762 30 mg QD MM

Reporting group description

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

Reporting group title

Part 1: GSK525762 40 mg QD

Reporting group description

Participants were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

Part 1: GSK525762 40 mg QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD AML

Reporting group description

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD NHL

Reporting group description

Participants with Non-Hodgkin’s Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 60 mg QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 1: GSK525762 75 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD

Reporting group description

Participants were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 80 mg QD NHL

Reporting group description

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

Part 1: GSK525762 100 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

Reporting group title

Part 1: GSK525762 120 mg QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

Reporting group title

Part 2: GSK525762 60 mg QD CTCL

Reporting group description

Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

Part 2: GSK525762 75 mg QD MDS

Reporting group description

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

Part 2: GSK525762 80 mg QD CTCL

Reporting group description

Participants CTCL were administered once daily oral dose of 80 mg GSK525762

Subject analysis set title

Part 2: GSK525762 75 mg QD MDS

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

Primary: Part 1: Number of participants with non-serious adverse events (AEs) and serious adverse events (SAEs) and AE leading to discontinuation (AELD)

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End point title

Part 1: Number of participants with non-serious adverse events (AEs) and serious adverse events (SAEs) and AE leading to discontinuation (AELD) ^[1] ^[2]

End point description

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment. All Treated Population consists of all participants that received at least one dose of study treatment.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[3]	1 ^[4]	1 ^[5]	5 ^[6]	1 ^[7]	4 ^[8]	8 ^[9]	18 ^[10]	3 ^[11]	8 ^[12]	1 ^[13]	7 ^[14]	7 ^[15]	16 ^[16]	6 ^[17]
Units: Participants
Non-serious AEs	1	1	1	5	1	4	8	18	3	8	1	7	7	16	6
SAEs	1	0	0	4	0	3	6	12	2	8	1	6	7	14	6
AELD	0	0	0	1	0	1	3	3	0	2	0	3	1	8	2

Notes
[3] - All Treated Population
[4] - All Treated Population
[5] - All Treated Population
[6] - All Treated Population
[7] - All Treated Population
[8] - All Treated Population
[9] - All Treated Population
[10] - All Treated Population
[11] - All Treated Population
[12] - All Treated Population
[13] - All Treated Population
[14] - All Treated Population
[15] - All Treated Population
[16] - All Treated Population
[17] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with Dose Limiting Toxicities (DLTs)

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End point title

Part 1: Number of participants with Dose Limiting Toxicities (DLTs) ^[18] ^[19]

End point description

An event was considered DLT if it occurred within first 3weeks of treatment & met one of following criteria:unless it was clearly established that event is unrelated to treatment:Grade4 neutropenia persisting for >=7 days/febrile neutropenia not responding to treatment within 24hours, Grade4 thrombocytopenia lasting more than 7day & not responding to transfusions/Grade3 thrombocytopenia associated with bleeding (>10milliliter [mL]), Drug-related Grade 3/4 non-hematologic toxicity as described in National Cancer Institute-Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 4.0, Drug-related Grade2 non-hematological toxicity, Grade2 Troponin T elevation(central laboratory>Upper Limit of Normal[ULN]),measured on two separate occasions within 48 hours, Treatment delay of 14 days/greater due to unresolved drug-related toxicity,ALT>=3xULN+bilirubin>=2xULN(>35% direct)/Alanine aminotransferase(ALT) between 3-5xULN with bilirubin<2xULN but with hepatitis symptom/rash/ALT>=5xULN.

End point type

Primary

End point timeframe

Up to 3 weeks

Notes
[18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[20]

1 ^[21]

1 ^[22]

5 ^[23]

1 ^[24]

4 ^[25]

8 ^[26]

18 ^[27]

3 ^[28]

8 ^[29]

1 ^[30]

7 ^[31]

7 ^[32]

16 ^[33]

6 ^[34]

Units: Participants

Notes
[20] - All Treated Population
[21] - All Treated Population
[22] - All Treated Population
[23] - All Treated Population
[24] - All Treated Population
[25] - All Treated Population
[26] - All Treated Population
[27] - All Treated Population
[28] - All Treated Population
[29] - All Treated Population
[30] - All Treated Population
[31] - All Treated Population
[32] - All Treated Population
[33] - All Treated Population
[34] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with dose reductions

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End point title

Part 1: Number of participants with dose reductions ^[35] ^[36]

End point description

Number of participants with dose reductions due to any reason is presented.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[37]

1 ^[38]

1 ^[39]

5 ^[40]

1 ^[41]

4 ^[42]

8 ^[43]

18 ^[44]

3 ^[45]

8 ^[46]

1 ^[47]

7 ^[48]

7 ^[49]

16 ^[50]

6 ^[51]

Units: Participants

Notes
[37] - All Treated Population
[38] - All Treated Population
[39] - All Treated Population
[40] - All Treated Population
[41] - All Treated Population
[42] - All Treated Population
[43] - All Treated Population
[44] - All Treated Population
[45] - All Treated Population
[46] - All Treated Population
[47] - All Treated Population
[48] - All Treated Population
[49] - All Treated Population
[50] - All Treated Population
[51] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with any dose interruptions or delays

Top of page

End point title

Part 1: Number of participants with any dose interruptions or delays ^[52] ^[53]

End point description

Number of participants with any dose interruptions/ delays is presented.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[54]

1 ^[55]

1 ^[56]

5 ^[57]

1 ^[58]

4 ^[59]

8 ^[60]

18 ^[61]

3 ^[62]

8 ^[63]

1 ^[64]

7 ^[65]

7 ^[66]

16 ^[67]

6 ^[68]

Units: Participants

Notes
[54] - All Treated Population
[55] - All Treated Population
[56] - All Treated Population
[57] - All Treated Population
[58] - All Treated Population
[59] - All Treated Population
[60] - All Treated Population
[61] - All Treated Population
[62] - All Treated Population
[63] - All Treated Population
[64] - All Treated Population
[65] - All Treated Population
[66] - All Treated Population
[67] - All Treated Population
[68] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with grade change from Baseline in clinical chemistry parameters

Top of page

End point title

Part 1: Number of participants with grade change from Baseline in clinical chemistry parameters ^[69] ^[70]

End point description

Blood samples were collected for analysis of following clinical chemistry parameters:glucose, Pro. INR,albumin,amylase,alanine aminotransferase (ALT),aspartate aminotransferase (AST), bilirubin,calcium,calcium ionized,cholesterol,creatinine, creatinekinase,lipase,potassium,magnesium,sodium,triglycerides,alkaline phosphatase (ALP). Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1:mild; Grade 2:moderate; Grade 3:severe/medically significant; Grade 4:life-threatening consequences;Grade 5: death related to AE. Higher grade indicates greater severity.An increase was defined as increase relative to Baseline. Baseline was most recent,non-missing value prior to/on first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.Only those participants with data available at specified data points were analyzed(represented by n=X in category titles).77777 indicates data is not available.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[69] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[71]	1 ^[72]	1 ^[73]	5 ^[74]	1 ^[75]	4 ^[76]	8 ^[77]	18 ^[78]	3 ^[79]	8 ^[80]	1 ^[81]	7 ^[82]	7 ^[83]	16 ^[84]	6 ^[85]
Units: Participants
Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	1	0	1	3	1	3	6	16	2	8	1	6	6	15	3
Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4	77777	0	1	3	0	1	3	10	1	3	77777	4	5	8	3
Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	1	0	1	1	1	0	4	7	1	3	1	3	3	6	1
ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6	0	0	0	1	0	1	1	4	1	1	0	1	3	4	0
Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5	0	1	0	1	1	0	0	5	2	0	0	3	4	3	0
AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6	0	0	1	1	0	0	1	5	1	0	0	3	3	4	1
Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6	1	0	1	0	1	1	6	8	1	7	1	6	5	12	4
Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	0	0	0	2	0	1	5	6	0	5	0	4	1	6	5
Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6	1	0	1	1	1	3	1	2	0	3	0	3	3	6	2
Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3	0	0	1	1	0	1	0	1	1	1	1	2	2	3	0
Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6	0	0	0	1	0	1	2	3	1	0	0	1	2	4	0
Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	0	0	0	1	0	1	4	5	1	1	0	3	2	6	1
Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6	0	0	0	0	1	1	0	5	0	2	0	2	3	0	1
Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6	1	0	1	1	0	3	3	4	2	5	1	5	4	7	3
Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	1	0	0	1	1	2	3	4	2	1	1	4	5	8	2
Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	1	0	0	3	1	3	3	6	1	4	1	4	2	9	3
Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3	1	0	1	2	1	2	1	4	1	3	1	5	2	8	2
ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6	0	0	0	1	0	2	0	2	1	0	1	4	3	1	1

Notes
[71] - All Treated Population
[72] - All Treated Population
[73] - All Treated Population
[74] - All Treated Population
[75] - All Treated Population
[76] - All Treated Population
[77] - All Treated Population
[78] - All Treated Population
[79] - All Treated Population
[80] - All Treated Population
[81] - All Treated Population
[82] - All Treated Population
[83] - All Treated Population
[84] - All Treated Population
[85] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with grade change from Baseline in hematology parameters

Top of page

End point title

Part 1: Number of participants with grade change from Baseline in hematology parameters ^[86] ^[87]

End point description

Blood samples were collected for analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets & leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).77777 indicates data is not available.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[86] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[88]	1 ^[89]	1 ^[90]	5 ^[91]	1 ^[92]	4 ^[93]	8 ^[94]	18 ^[95]	3 ^[96]	8 ^[97]	1 ^[98]	7 ^[99]	7 ^[100]	16 ^[101]	6 ^[102]
Units: Participants
Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	1	0	0	2	0	2	3	13	3	6	1	4	6	9	3
Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6	0	0	77777	3	1	3	4	11	2	5	1	6	3	10	5
Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5	0	0	77777	4	0	3	1	6	2	5	0	2	5	3	1
Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	0	0	1	4	1	4	4	17	3	4	1	5	7	11	2
Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6	0	0	1	4	1	3	2	9	3	4	1	3	4	9	3

Notes
[88] - All Treated Population
[89] - All Treated Population
[90] - All Treated Population
[91] - All Treated Population
[92] - All Treated Population
[93] - All Treated Population
[94] - All Treated Population
[95] - All Treated Population
[96] - All Treated Population
[97] - All Treated Population
[98] - All Treated Population
[99] - All Treated Population
[100] - All Treated Population
[101] - All Treated Population
[102] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method

Top of page

End point title

Part 1: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method ^[103] ^[104]

End point description

Urine samples were collected to assess glucose, ketones, occult blood, urine protein, and monoclonal protein (monoclonal pro). The dipstick test gave results in semi-quantitative manner, & results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). 77777 indicates data is not available.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[103] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[105]	1 ^[106]	1 ^[107]	4 ^[108]	1 ^[109]	4 ^[110]	5 ^[111]	15 ^[112]	3 ^[113]	7 ^[114]	1 ^[115]	6 ^[116]	5 ^[117]	11 ^[118]	2 ^[119]
Units: Participants
Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1	0	0	0	1	0	1	1	0	0	2	77777	0	2	2	1
Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2	1	0	0	0	1	0	0	1	0	2	1	1	0	3	1
Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2	1	0	1	3	0	2	3	4	3	3	1	4	2	4	1
Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1	0	0	1	2	1	2	1	5	0	3	77777	0	3	3	1
Monoclonal pro, n=0,0,0,0,0,1,0,0,2,0,0,0,0,0,0	77777	77777	77777	77777	77777	0	77777	77777	0	77777	77777	77777	77777	77777	77777

Notes
[105] - All Treated Population
[106] - All Treated Population
[107] - All Treated Population
[108] - All Treated Population
[109] - All Treated Population
[110] - All Treated Population
[111] - All Treated Population
[112] - All Treated Population
[113] - All Treated Population
[114] - All Treated Population
[115] - All Treated Population
[116] - All Treated Population
[117] - All Treated Population
[118] - All Treated Population
[119] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature

Top of page

End point title

Part 1: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature ^[120] ^[121]

End point description

Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low <60 beats per minute [bpm] and high >100 bpm); For body temperature (<=35 degrees Celsius or >=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so percentages may not add to 100%. Baseline was most recent, non-missing value prior to or on first study treatment dose date. Only those participants with data available at the specified data points were analyzed.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[120] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[121] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[122]	1 ^[123]	1 ^[124]	5 ^[125]	1 ^[126]	4 ^[127]	7 ^[128]	18 ^[129]	3 ^[130]	8 ^[131]	1 ^[132]	7 ^[133]	7 ^[134]	16 ^[135]	6 ^[136]
Units: Participants
Pulse rate, To Low	0	0	1	0	0	0	2	0	0	0	0	0	0	1	0
Pulse rate, To Normal or No change	0	1	0	2	0	2	4	8	1	5	1	1	1	8	4
Pulse Rate, To High	1	0	0	3	1	2	2	10	2	3	0	6	6	8	2
Temperature, To Low	0	0	0	0	0	1	0	0	0	0	0	0	1	1	0
Temperature, To Normal or No Change	0	1	1	4	1	2	3	15	3	7	1	1	6	7	6
Temperature, To High	1	0	0	1	0	1	4	3	0	1	0	6	0	8	0

Notes
[122] - All Treated Population
[123] - All Treated Population
[124] - All Treated Population
[125] - All Treated Population
[126] - All Treated Population
[127] - All Treated Population
[128] - All Treated Population
[129] - All Treated Population
[130] - All Treated Population
[131] - All Treated Population
[132] - All Treated Population
[133] - All Treated Population
[134] - All Treated Population
[135] - All Treated Population
[136] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with increase to Grade 3 from Baseline in vital signs: Diastolic Blood pressure (DBP) and Systolic Blood pressure (SBP)

Top of page

End point title

Part 1: Number of participants with increase to Grade 3 from Baseline in vital signs: Diastolic Blood pressure (DBP) and Systolic Blood pressure (SBP) ^[137] ^[138]

End point description

DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (<=120 millimeter of mercury [mmHg]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (>=160 mmHg). For DBP: Grade 0 (<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[137] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[138] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[139]	1 ^[140]	1 ^[141]	5 ^[142]	1 ^[143]	4 ^[144]	7 ^[145]	18 ^[146]	3 ^[147]	8 ^[148]	1 ^[149]	7 ^[150]	7 ^[151]	16 ^[152]	6 ^[153]
Units: Participants
DBP	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0
SBP	0	0	0	1	1	0	1	1	0	1	1	4	1	4	4

Notes
[139] - All Treated Population
[140] - All Treated Population
[141] - All Treated Population
[142] - All Treated Population
[143] - All Treated Population
[144] - All Treated Population
[145] - All Treated Population
[146] - All Treated Population
[147] - All Treated Population
[148] - All Treated Population
[149] - All Treated Population
[150] - All Treated Population
[151] - All Treated Population
[152] - All Treated Population
[153] - All Treated Population

No statistical analyses for this end point

Primary: Part 1: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading)

Top of page

End point title

Part 1: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading) ^[154] ^[155]

End point description

12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

End point type

Primary

End point timeframe

Up to 86.9 weeks

Notes
[154] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[155] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[156]	1 ^[157]	1 ^[158]	5 ^[159]	1 ^[160]	4 ^[161]	8 ^[162]	18 ^[163]	3 ^[164]	8 ^[165]	1 ^[166]	7 ^[167]	7 ^[168]	16 ^[169]	6 ^[170]
Units: Participants
Abnormal-Clinically significant	0	0	1	1	0	1	1	1	0	3	0	0	2	4	1
Abnormal-Not Clinically significant	1	1	0	4	1	3	6	17	3	5	1	7	5	12	5

Notes
[156] - All Treated Population
[157] - All Treated Population
[158] - All Treated Population
[159] - All Treated Population
[160] - All Treated Population
[161] - All Treated Population
[162] - All Treated Population
[163] - All Treated Population
[164] - All Treated Population
[165] - All Treated Population
[166] - All Treated Population
[167] - All Treated Population
[168] - All Treated Population
[169] - All Treated Population
[170] - All Treated Population

No statistical analyses for this end point

Primary: Part 2: Objective response rate (ORR) (MDS cohort)

Top of page

End point title

Part 2: Objective response rate (ORR) (MDS cohort) ^[171] ^[172]

End point description

ORR for MDS cohort is defined as the percentage of participants achieving Complete Response (CR), Marrow CR, CRp (as per CR but platelet count <100 x 10^9 cells/Liter[L]), CRi (as per CR but platelet count <100 x 10^9cells/L or neutrophil count <1 x 10^9 cells/L), or Partial Response (PR) per response criteria. Complete response is defined as bone marrow <=5% myeloblasts with normal maturation of all cell lines, with hemoglobin concentration of >=11 grams per deciliter (g/dL), absolute neutrophil count >=1 x 10^9 cells/L, platelet count >=100x10^9 cells/L and 0% blasts in the peripheral blood. Marrow CR is defined as Bone marrow <=5% myeloblasts and decrease by >=50% over pre-treatment. Objective response rate was determined by the investigator according to international myeloma working group (IMWG) response criteria.

End point type

Primary

End point timeframe

Up to 36.4 weeks

Notes
[171] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	16 ^[173]
Units: Percentage of participants
number (confidence interval 95%)	25 (7.3 to 52.4)

Notes
[173] - All Treated Population

No statistical analyses for this end point

Primary: Part 2: Objective response rate lasting at least 4 months (ORR4) (CTCL cohorts)

Top of page

End point title

Part 2: Objective response rate lasting at least 4 months (ORR4) (CTCL cohorts) ^[174] ^[175]

End point description

ORR4 for CTCL cohorts is defined as the percentage of participants that have achieved a CR or PR lasting at least 4 months per global response criteria and the modified severity weighted assessment tool (mSWAT). ORR4 and 95% exact confidence interval is presented.

End point type

Primary

End point timeframe

Up to 36.4 weeks

Notes
[174] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[175] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[176]	1 ^[177]
Units: Percentage of participants
number (confidence interval 95%)	0 (0 to 41)	0 (0 to 97.5)

Notes
[176] - All Treated Population
[177] - All Treated Population

No statistical analyses for this end point

Secondary: Part 1: Overall response rate (ORR)- Investigator assessment

Top of page

End point title

Part 1: Overall response rate (ORR)- Investigator assessment ^[178]

End point description

ORR is defined as the percentage of participants achieving stringent complete response (sCR), very good partial response (VGPR), partial response (PR) or minimal response (MR) for multiple myeloma (MM); CR or PR for Non-Hodgkin’s Lymphoma (NHL); CR, CRp, CRi or PR for Acute Myeloid Leukemia (AML); CR, MR or PR for Myelodysplastic Syndrome (MDS) using the International Working Group (IWG) response criteria and IWG response criteria in myelodysplasia.

End point type

Secondary

End point timeframe

Up to 86.9 weeks

Notes
[178] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[179]

1 ^[180]

1 ^[181]

5 ^[182]

1 ^[183]

4 ^[184]

8 ^[185]

18 ^[186]

3 ^[187]

8 ^[188]

1 ^[189]

7 ^[190]

7 ^[191]

16 ^[192]

6 ^[193]

Units: Percentage of participants

number (confidence interval 95%)

0 (0 to 97.5)

0 (0 to 52.2)

0 (0 to 97.5)

0 (0 to 60.2)

25 (3.2 to 65.1)

6 (0.1 to 27.3)

0 (0 to 70.8)

0 (0 to 36.9)

0 (0 to 97.5)

14 (0.4 to 57.9)

29 (3.7 to 71.0)

13 (1.6 to 38.3)

17 (0.4 to 64.1)

Notes
[179] - All Treated Population
[180] - All Treated Population
[181] - All Treated Population
[182] - All Treated Population
[183] - All Treated Population
[184] - All Treated Population
[185] - All Treated Population
[186] - All Treated Population
[187] - All Treated Population
[188] - All Treated Population
[189] - All Treated Population
[190] - All Treated Population
[191] - All Treated Population
[192] - All Treated Population
[193] - All Treated Population

No statistical analyses for this end point

Secondary: Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 following single dose administration

Top of page

End point title

Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 following single dose administration ^[194]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants in the All Treated Population for whom a PK sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). 99999 indicates that, geometric coefficient of variation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[194] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[195]	1 ^[196]	1 ^[197]	5 ^[198]	1 ^[199]	4 ^[200]	8 ^[201]	18 ^[202]	3 ^[203]	8 ^[204]	1 ^[205]	6 ^[206]	7 ^[207]	16 ^[208]	6 ^[209]
Units: Hours*nanograms per milliliter
geometric mean (geometric coefficient of variation)
AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6	460.48 ( 99999 )	1024.49 ( 99999 )	2881.41 ( 99999 )	2146.54 ( 31.68 )	3317.10 ( 99999 )	2510.55 ( 71.29 )	6424.74 ( 22.42 )	5918.90 ( 52.85 )	3695.32 ( 62.01 )	7980.72 ( 45.28 )	5944.52 ( 99999 )	8394.69 ( 34.31 )	5017.96 ( 44.17 )	13520.57 ( 46.29 )	13688.54 ( 43.80 )
AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5	466.81 ( 99999 )	1092.28 ( 99999 )	3054.11 ( 99999 )	2217.32 ( 32.55 )	3465.49 ( 99999 )	2546.49 ( 72.05 )	6951.06 ( 25.12 )	6214.97 ( 60.67 )	3874.05 ( 63.27 )	8248.45 ( 47.87 )	6032.36 ( 99999 )	9734.83 ( 29.60 )	5114.61 ( 44.76 )	14635.17 ( 52.35 )	17021.44 ( 35.37 )

Notes
[195] - PK Population
[196] - PK Population
[197] - PK Population
[198] - PK Population
[199] - PK Population
[200] - PK Population
[201] - PK Population
[202] - PK Population
[203] - PK Population
[204] - PK Population
[205] - PK Population
[206] - PK Population
[207] - PK Population
[208] - PK Population
[209] - PK Population

No statistical analyses for this end point

Secondary: Part 1: AUC(0-24) and Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK525762 following repeat dose administration

Top of page

End point title

Part 1: AUC(0-24) and Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK525762 following repeat dose administration ^[210]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant. AUC(0-24) represents AUC(0-tau) for repeat dose.

End point type

Secondary

End point timeframe

Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[210] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[211]	1 ^[212]	1 ^[213]	4 ^[214]	1 ^[215]	4 ^[216]	3 ^[217]	11 ^[218]	2 ^[219]	7 ^[220]	1 ^[221]	6 ^[222]	4 ^[223]	11 ^[224]	2 ^[225]
Units: Hours*nanograms per milliliter
geometric mean (geometric coefficient of variation)
AUC(0-24)	476.71 ( 99999 )	656.93 ( 99999 )	1855.07 ( 99999 )	1908.18 ( 27.53 )	2490.25 ( 99999 )	1702.37 ( 58.17 )	6271.43 ( 38.76 )	3576.49 ( 30.59 )	931.02 ( 53.64 )	5883.76 ( 48.48 )	5188.25 ( 99999 )	6892.57 ( 71.96 )	2994.24 ( 37.27 )	9440.98 ( 84.11 )	5296.46 ( 8.89 )
AUC(0-tau)	476.71 ( 99999 )	656.93 ( 99999 )	1855.07 ( 99999 )	1908.18 ( 27.53 )	2490.25 ( 99999 )	1702.37 ( 58.17 )	6271.43 ( 38.76 )	3576.49 ( 30.59 )	931.02 ( 53.64 )	5883.76 ( 48.48 )	5188.25 ( 99999 )	6892.57 ( 71.96 )	2994.24 ( 37.27 )	9440.98 ( 84.11 )	5296.46 ( 8.89 )

Notes
[211] - PK Population
[212] - PK Population
[213] - PK Population
[214] - PK Population
[215] - PK Population
[216] - PK Population
[217] - PK Population
[218] - PK Population
[219] - PK Population
[220] - PK Population
[221] - PK Population
[222] - PK Population
[223] - PK Population
[224] - PK Population
[225] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Maximum Observed Concentration (Cmax) and Minimum plasma concentration (Cmin) of GSK525762 following single dose administration

Top of page

End point title

Part 1: Maximum Observed Concentration (Cmax) and Minimum plasma concentration (Cmin) of GSK525762 following single dose administration ^[226]

End point description

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[226] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[227]	1 ^[228]	1 ^[229]	5 ^[230]	1 ^[231]	4 ^[232]	8 ^[233]	18 ^[234]	3 ^[235]	8 ^[236]	1 ^[237]	6 ^[238]	7 ^[239]	16 ^[240]	6 ^[241]
Units: Nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)
Cmax	90.56 ( 99999 )	116.69 ( 99999 )	559.14 ( 99999 )	442.77 ( 31.83 )	513.03 ( 99999 )	660.79 ( 71.94 )	853.03 ( 31.1 )	1158.66 ( 28.58 )	813.87 ( 27.91 )	1728.80 ( 35.37 )	1248.10 ( 99999 )	1444.42 ( 29.92 )	1073.51 ( 38.46 )	2335.99 ( 23.05 )	1793.39 ( 42.16 )
Cmin	1.11 ( 99999 )	27.86 ( 99999 )	20.62 ( 99999 )	7.55 ( 73.07 )	21.20 ( 99999 )	13.25 ( 71.79 )	107.30 ( 68.40 )	50.49 ( 139.83 )	29.39 ( 47.67 )	37.92 ( 80.33 )	129.76 ( 99999 )	71.43 ( 112.42 )	27.89 ( 115.67 )	89.96 ( 112.80 )	138.75 ( 111.14 )

Notes
[227] - PK Population
[228] - PK Population
[229] - PK Population
[230] - PK Population
[231] - PK Population
[232] - PK Population
[233] - PK Population
[234] - PK Population
[235] - PK Population
[236] - PK Population
[237] - PK Population
[238] - PK Population
[239] - PK Population
[240] - PK Population
[241] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Cmax and Cmin of GSK525762 following repeat dose administration

Top of page

End point title

Part 1: Cmax and Cmin of GSK525762 following repeat dose administration ^[242]

End point description

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[242] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 5 mg QD	Part 1: GSK525762 10 mg QD	Part 1: GSK525762 20 mg QD	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD AML	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD	Part 1: GSK525762 80 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML	Part 1: GSK525762 120 mg QD AML
Number of subjects analysed	1 ^[243]	1 ^[244]	1 ^[245]	4 ^[246]	1 ^[247]	4 ^[248]	3 ^[249]	11 ^[250]	2 ^[251]	7 ^[252]	1 ^[253]	6 ^[254]	4 ^[255]	11 ^[256]	2 ^[257]
Units: Nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)
Cmax	102.86 ( 99999 )	118.59 ( 99999 )	550.01 ( 99999 )	387.66 ( 52.41 )	557.60 ( 99999 )	566.59 ( 57.75 )	1070.32 ( 37.26 )	1179.42 ( 28.10 )	512.78 ( 48.37 )	1384.46 ( 35.35 )	1752.86 ( 99999 )	1314.21 ( 58.58 )	725.29 ( 46.79 )	1587.25 ( 50.83 )	921.35 ( 52.16 )
Cmin	1.47 ( 99999 )	5.03 ( 99999 )	3.92 ( 99999 )	7.72 ( 103.48 )	8.66 ( 99999 )	2.36 ( 84.21 )	57.75 ( 82.69 )	7.03 ( 51.10 )	1.63 ( 141.42 )	14.00 ( 112.58 )	21.02 ( 99999 )	50.89 ( 123.69 )	4.64 ( 73.29 )	55.63 ( 163.06 )	14.96 ( 64.95 )

Notes
[243] - PK Population
[244] - PK Population
[245] - PK Population
[246] - PK Population
[247] - PK Population
[248] - PK Population
[249] - PK Population
[250] - PK Population
[251] - PK Population
[252] - PK Population
[253] - PK Population
[254] - PK Population
[255] - PK Population
[256] - PK Population
[257] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Trough concentration (Ctau) of GSK525762 following repeat dose administration

Top of page

End point title

Part 1: Trough concentration (Ctau) of GSK525762 following repeat dose administration ^[258]

End point description

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose on Days 4, 6 and 7

Notes
[258] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[259]

1 ^[260]

1 ^[261]

4 ^[262]

1 ^[263]

4 ^[264]

3 ^[265]

11 ^[266]

2 ^[267]

7 ^[268]

1 ^[269]

6 ^[270]

4 ^[271]

11 ^[272]

2 ^[273]

Units: Nanograms per milliliter (ng/mL)

geometric mean (geometric coefficient of variation)

0.91 ( 99999 )

3.90 ( 99999 )

3.76 ( 99999 )

4.88 ( 78.94 )

8.12 ( 99999 )

2.26 ( 114.63 )

32.85 ( 88.47 )

5.99 ( 41.92 )

0.03 ( 128.56 )

13.21 ( 102.35 )

2.08 ( 99999 )

15.77 ( 123.78 )

2.25 ( 92.05 )

42.18 ( 139.74 )

14.34 ( 68.62 )

Notes
[259] - PK Population
[260] - PK Population
[261] - PK Population
[262] - PK Population
[263] - PK Population
[264] - PK Population
[265] - PK Population
[266] - PK Population
[267] - PK Population
[268] - PK Population
[269] - PK Population
[270] - PK Population
[271] - PK Population
[272] - PK Population
[273] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Time of maximum concentration (Tmax) of GSK525762 following single dose administration

Top of page

End point title

Part 1: Time of maximum concentration (Tmax) of GSK525762 following single dose administration ^[274]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[274] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[275]

1 ^[276]

1 ^[277]

5 ^[278]

1 ^[279]

4 ^[280]

8 ^[281]

18 ^[282]

3 ^[283]

8 ^[284]

1 ^[285]

6 ^[286]

7 ^[287]

16 ^[288]

6 ^[289]

Units: Hour

median (full range (min-max))

0.62 (-66666 to 66666)

2.00 (-66666 to 66666)

1.00 (-66666 to 66666)

1.00 (0.5 to 1.0)

1.00 (-66666 to 66666)

0.78 (0.4 to 2.0)

1.56 (0.3 to 2.1)

1.00 (0.3 to 4.1)

1.00 (0.5 to 2.2)

0.86 (0.5 to 2.1)

1.28 (-66666 to 66666)

1.03 (0.5 to 2.0)

1.00 (0.3 to 1.2)

0.92 (0.3 to 4.0)

1.58 (0.2 to 4.1)

Notes
[275] - PK Population
[276] - PK Population
[277] - PK Population
[278] - PK Population
[279] - PK Population
[280] - PK Population
[281] - PK Population
[282] - PK Population
[283] - PK Population
[284] - PK Population
[285] - PK Population
[286] - PK Population
[287] - PK Population
[288] - PK Population
[289] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Tmax of GSK525762 following repeat dose administration

Top of page

End point title

Part 1: Tmax of GSK525762 following repeat dose administration ^[290]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[290] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[291]

1 ^[292]

1 ^[293]

4 ^[294]

1 ^[295]

4 ^[296]

3 ^[297]

11 ^[298]

2 ^[299]

7 ^[300]

1 ^[301]

6 ^[302]

4 ^[303]

11 ^[304]

2 ^[305]

Units: Hour

median (full range (min-max))

0.67 (-66666 to 66666)

0.00 (-66666 to 66666)

0.83 (-66666 to 66666)

1.26 (0.5 to 2.0)

0.50 (-66666 to 66666)

0.78 (0.5 to 1.2)

0.58 (0.5 to 2.0)

0.50 (0.3 to 2.0)

0.63 (0.3 to 1.0)

0.60 (0.3 to 0.6)

0.50 (-66666 to 66666)

0.98 (0.5 to 2.0)

1.06 (0.6 to 2.0)

2.00 (0.5 to 4.0)

2.33 (0.5 to 4.2)

Notes
[291] - PK Population
[292] - PK Population
[293] - PK Population
[294] - PK Population
[295] - PK Population
[296] - PK Population
[297] - PK Population
[298] - PK Population
[299] - PK Population
[300] - PK Population
[301] - PK Population
[302] - PK Population
[303] - PK Population
[304] - PK Population
[305] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Terminal half life (T1/2) of GSK525762 following single dose administration

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End point title

Part 1: Terminal half life (T1/2) of GSK525762 following single dose administration ^[306]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[306] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[307]

1 ^[308]

1 ^[309]

5 ^[310]

1 ^[311]

4 ^[312]

8 ^[313]

17 ^[314]

3 ^[315]

8 ^[316]

1 ^[317]

5 ^[318]

7 ^[319]

16 ^[320]

5 ^[321]

Units: Hour

median (full range (min-max))

4.01 (-66666 to 66666)

5.75 (-66666 to 66666)

6.27 (-66666 to 66666)

4.55 (1.4 to 6.4)

5.10 (-66666 to 66666)

4.07 (3.5 to 4.6)

6.48 (5.2 to 10.3)

3.96 (2.9 to 9.3)

5.55 (1.4 to 8.1)

4.57 (3.3 to 6.3)

4.15 (-66666 to 66666)

4.75 (4.1 to 7.4)

4.06 (3.0 to 5.8)

5.66 (1.9 to 9.7)

6.53 (4.7 to 7.5)

Notes
[307] - PK Population
[308] - PK Population
[309] - PK Population
[310] - PK Population
[311] - PK Population
[312] - PK Population
[313] - PK Population
[314] - PK Population
[315] - PK Population
[316] - PK Population
[317] - PK Population
[318] - PK Population
[319] - PK Population
[320] - PK Population
[321] - PK Population

No statistical analyses for this end point

Secondary: Part 1: T1/2 of GSK525762 following repeat dose administration

Top of page

End point title

Part 1: T1/2 of GSK525762 following repeat dose administration ^[322]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[322] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[323]

1 ^[324]

1 ^[325]

4 ^[326]

1 ^[327]

4 ^[328]

3 ^[329]

11 ^[330]

2 ^[331]

6 ^[332]

1 ^[333]

6 ^[334]

4 ^[335]

11 ^[336]

2 ^[337]

Units: Hour

median (full range (min-max))

3.68 (-66666 to 66666)

5.64 (-66666 to 66666)

4.70 (-66666 to 66666)

4.15 (2.9 to 6.4)

4.39 (-66666 to 66666)

4.39 (3.2 to 5.8)

6.48 (3.4 to 7.8)

3.51 (3.0 to 5.3)

1.96 (1.7 to 2.3)

3.97 (3.1 to 5.3)

2.54 (-66666 to 66666)

4.98 (2.4 to 5.9)

3.22 (2.2 to 3.7)

5.51 (3.2 to 8.6)

4.09 (3.8 to 4.4)

Notes
[323] - PK Population
[324] - PK Population
[325] - PK Population
[326] - PK Population
[327] - PK Population
[328] - PK Population
[329] - PK Population
[330] - PK Population
[331] - PK Population
[332] - PK Population
[333] - PK Population
[334] - PK Population
[335] - PK Population
[336] - PK Population
[337] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Time invariance (RS) of GSK525762

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End point title

Part 1: Time invariance (RS) of GSK525762 ^[338]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 99999 indicates geometric coefficient of variation could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[338] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[339]

1 ^[340]

1 ^[341]

5 ^[342]

1 ^[343]

4 ^[344]

3 ^[345]

10 ^[346]

2 ^[347]

7 ^[348]

1 ^[349]

7 ^[350]

4 ^[351]

11 ^[352]

1 ^[353]

Units: Ratio

geometric mean (geometric coefficient of variation)

1.02 ( 99999 )

0.60 ( 99999 )

0.61 ( 99999 )

0.71 ( 35.82 )

0.72 ( 99999 )

0.67 ( 18.60 )

0.98 ( 11.73 )

0.65 ( 31.37 )

0.32 ( 53.56 )

0.78 ( 46.56 )

0.86 ( 99999 )

0.91 ( 36.22 )

0.74 ( 19.36 )

0.76 ( 84.74 )

0.54 ( 99999 )

Notes
[339] - PK Population
[340] - PK Population
[341] - PK Population
[342] - PK Population
[343] - PK Population
[344] - PK Population
[345] - PK Population
[346] - PK Population
[347] - PK Population
[348] - PK Population
[349] - PK Population
[350] - PK Population
[351] - PK Population
[352] - PK Population
[353] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Accumulation ratio (RO) of GSK525762

Top of page

End point title

Part 1: Accumulation ratio (RO) of GSK525762 ^[354]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified data points were analyzed. 99999 indicates geometric coefficient of variation could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[354] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

Part 1: GSK525762 5 mg QD

Part 1: GSK525762 10 mg QD

Part 1: GSK525762 20 mg QD

Part 1: GSK525762 30 mg QD MM

Part 1: GSK525762 40 mg QD

Part 1: GSK525762 40 mg QD MM

Part 1: GSK525762 60 mg QD AML

Part 1: GSK525762 60 mg QD NHL

Part 1: GSK525762 60 mg QD MM

Part 1: GSK525762 75 mg QD AML

Part 1: GSK525762 80 mg QD

Part 1: GSK525762 80 mg QD AML

Part 1: GSK525762 80 mg QD NHL

Part 1: GSK525762 100 mg QD AML

Part 1: GSK525762 120 mg QD AML

Number of subjects analysed

1 ^[355]

1 ^[356]

1 ^[357]

4 ^[358]

1 ^[359]

4 ^[360]

3 ^[361]

11 ^[362]

2 ^[363]

7 ^[364]

1 ^[365]

5 ^[366]

4 ^[367]

11 ^[368]

2 ^[369]

Units: Ratio

geometric mean (geometric coefficient of variation)

1.04 ( 99999 )

0.64 ( 99999 )

0.74 ( 36.67 )

0.75 ( 99999 )

0.68 ( 17.66 )

1.06 ( 13.47 )

0.67 ( 29.24 )

0.33 ( 47.64 )

0.81 ( 45.70 )

0.87 ( 99999 )

1.01 ( 33.69 )

0.75 ( 20.27 )

0.81 ( 82.45 )

0.71 ( 24.96 )

Notes
[355] - PK Population
[356] - PK Population
[357] - PK Population
[358] - PK Population
[359] - PK Population
[360] - PK Population
[361] - PK Population
[362] - PK Population
[363] - PK Population
[364] - PK Population
[365] - PK Population
[366] - PK Population
[367] - PK Population
[368] - PK Population
[369] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after single dose administration

Top of page

End point title

Part 2: Apparent clearance (CL/F) of GSK525762 after single dose administration ^[370]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N” of 75 mg arm within this outcome measure is greater than overall “N” for 75 mg QD MDS & N=0 for 80 mg QC CTCL arm for this outcome measure.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.5 – 2 hour, 4 – 8 hours post-dose

Notes
[370] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[371]	17 ^[372]
Units: Liters per hour
arithmetic mean (standard deviation)	11.80 ( 3.39 )	7.98 ( 3.32 )

Notes
[371] - PK Population.
[372] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after repeat dose administration

Top of page

End point title

Part 2: Apparent clearance (CL/F) of GSK525762 after repeat dose administration ^[373]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N=0” for 80 mg QD arm within this outcome measure.

End point type

Secondary

End point timeframe

Week 3 Day 1: pre-dose and at 0.5 – 2 hour, 4 – 8 hours post-dose

Notes
[373] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[374]	8 ^[375]
Units: Liters per hour
arithmetic mean (standard deviation)	11.80 ( 3.39 )	9.33 ( 4.01 )

Notes
[374] - PK Population
[375] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following single dose administration

Top of page

End point title

Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following single dose administration ^[376]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N” of 75 mg arm within this outcome measure is greater than overall “N” for 75 mg QD MDS N=0 for 80 mg QC CTCL arm for this outcome measure.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.5 – 2 hour, 4 – 8 hours post-dose

Notes
[376] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[377]	17 ^[378]
Units: Liters
arithmetic mean (standard deviation)	51.5 ( 19.50 )	47.9 ( 8.01 )

Notes
[377] - PK Population
[378] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following repeat dose administration

Top of page

End point title

Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following repeat dose administration ^[379]

End point description

Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N=0” for 80 mg QD arm within this outcome measure.

End point type

Secondary

End point timeframe

Week 3 Day 1: pre-dose and at 0.5 – 2 hour, 4 – 8 hours post-dose

Notes
[379] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[380]	8 ^[381]
Units: Liters
arithmetic mean (standard deviation)	51.5 ( 19.50 )	45.8 ( 9.92 )

Notes
[380] - PK population
[381] - PK population

No statistical analyses for this end point

Secondary: Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (active metabolite) following single dose administration

Top of page

End point title

Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (active metabolite) following single dose administration ^[382]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[382] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	5 ^[383]	1 ^[384]	15 ^[385]	2 ^[386]	8 ^[387]	6 ^[388]	15 ^[389]
Units: Hours*nanograms per milliliter
geometric mean (geometric coefficient of variation)
AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0	1368.11 ( 31.39 )	1891.48 ( 99999 )	3048.33 ( 22.85 )	3297.95 ( 68.31 )	3174.42 ( 40.63 )	3432.89 ( 39.76 )	2901.79 ( 52.33 )
AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0	1691.75 ( 28.96 )	2013.33 ( 99999 )	3684.96 ( 28.50 )	4499.65 ( 72.79 )	4003.48 ( 42.09 )	3908.15 ( 41.20 )	4714.85 ( 48.39 )

Notes
[383] - PK Population
[384] - PK Population
[385] - PK Population
[386] - PK Population
[387] - PK Population
[388] - PK Population
[389] - PK Population

No statistical analyses for this end point

Secondary: Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (active metabolite) following repeat dose administration

Top of page

End point title

Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (active metabolite) following repeat dose administration ^[390]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 12 mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant. AUC(0-tau) is AUC(0-24) for repeat dose.

End point type

Secondary

End point timeframe

Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[390] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[391]	1 ^[392]	9 ^[393]	2 ^[394]	7 ^[395]	4 ^[396]	10 ^[397]
Units: Hours*nanograms per milliliter
geometric mean (geometric coefficient of variation)
AUC(0-24)	1517.96 ( 33.88 )	1922.77 ( 99999 )	4870.28 ( 46.15 )	3838.35 ( 37.18 )	5312.66 ( 45.30 )	3379.85 ( 44.24 )	8534.92 ( 43.93 )
AUC(0-tau)	1517.96 ( 33.88 )	1922.77 ( 99999 )	4870.28 ( 46.15 )	3838.35 ( 37.18 )	5312.66 ( 45.30 )	3379.85 ( 44.24 )	8534.92 ( 43.93 )

Notes
[391] - PK Population
[392] - PK Population
[393] - PK Population
[394] - PK Population
[395] - PK Population
[396] - PK Population
[397] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following single dose administration

Top of page

End point title

Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following single dose administration ^[398]

End point description

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[398] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	5 ^[399]	1 ^[400]	15 ^[401]	3 ^[402]	8 ^[403]	7 ^[404]	16 ^[405]
Units: Nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)
Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0	109.45 ( 45.38 )	246.12 ( 99999 )	239.98 ( 26.75 )	361.30 ( 54.77 )	251.73 ( 49.71 )	325.42 ( 47.17 )	201.02 ( 56.94 )
Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0	2.47 ( 4.29 )	66.39 ( 99999 )	18.17 ( 116.63 )	10.83 ( 161.52 )	18.45 ( 71.98 )	12.66 ( 108.08 )	14.17 ( 99.02 )

Notes
[399] - PK Population
[400] - PK Population
[401] - PK Population
[402] - PK Population
[403] - PK Population
[404] - PK Population
[405] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following repeat dose administration ^[406]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[406] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[407]	1 ^[408]	9 ^[409]	2 ^[410]	7 ^[411]	4 ^[412]	11 ^[413]
Units: Nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)
Cmax	121.83 ( 26.75 )	282.72 ( 99999 )	453.89 ( 34.07 )	500.61 ( 22.83 )	445.47 ( 52.02 )	370.67 ( 35.23 )	557.92 ( 31.81 )
Cmin	27.14 ( 28.38 )	15.18 ( 99999 )	66.49 ( 81.56 )	40.88 ( 45.39 )	73.60 ( 88.34 )	38.71 ( 56.34 )	116.62 ( 74.25 )

Notes
[407] - PK Population.
[408] - PK Population.
[409] - PK Population.
[410] - PK Population.
[411] - PK Population.
[412] - PK Population.
[413] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Trough concentration (Ctau) of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 1: Trough concentration (Ctau) of GSK3529246 (active metabolite) following repeat dose administration ^[414]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose on Days 4, 6 and 7

Notes
[414] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[415]	1 ^[416]	9 ^[417]	2 ^[418]	7 ^[419]	4 ^[420]	10 ^[421]
Units: Nanograms per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	22.48 ( 36.13 )	13.26 ( 99999 )	64.57 ( 77.46 )	40.42 ( 43.96 )	76.23 ( 62.65 )	28.29 ( 94.01 )	178.76 ( 69.25 )

Notes
[415] - PK Population.
[416] - PK Population.
[417] - PK Population.
[418] - PK Population.
[419] - PK Population.
[420] - PK Population.
[421] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following single dose administration

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End point title

Part 1: Tmax of GSK3529246 (active metabolite) following single dose administration ^[422]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[422] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	5 ^[423]	1 ^[424]	15 ^[425]	3 ^[426]	8 ^[427]	7 ^[428]	16 ^[429]
Units: Hour
median (full range (min-max))	1.92 (0.9 to 4.1)	0.58 (-66666 to 66666)	2.10 (0.5 to 8.0)	4.00 (2.0 to 4.2)	3.15 (1.2 to 4.1)	2.08 (0.3 to 4.2)	4.03 (2.0 to 17.5)

Notes
[423] - PK Population
[424] - PK Population
[425] - PK Population
[426] - PK Population
[427] - PK Population
[428] - PK Population
[429] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 1: Tmax of GSK3529246 (active metabolite) following repeat dose administration ^[430]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 6 mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[430] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[431]	1 ^[432]	9 ^[433]	2 ^[434]	7 ^[435]	4 ^[436]	11 ^[437]
Units: Hour
median (full range (min-max))	2.48 (1.0 to 4.0)	0.60 (-66666 to 66666)	1.03 (0.5 to 4.0)	1.00 (1.0 to 1.0)	2.05 (0.6 to 4.0)	2.02 (1.2 to 4.1)	4.00 (0.9 to 10.1)

Notes
[431] - PK Population
[432] - PK Population
[433] - PK Population
[434] - PK Population
[435] - PK Population
[436] - PK Population
[437] - PK Population

No statistical analyses for this end point

Secondary: Part 1: T1/2 of GSK3529246 (active metabolite) following single dose administration

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End point title

Part 1: T1/2 of GSK3529246 (active metabolite) following single dose administration ^[438]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[438] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	5 ^[439]	1 ^[440]	11 ^[441]	2 ^[442]	6 ^[443]	6 ^[444]	7 ^[445]
Units: Hour
median (full range (min-max))	9.90 (5.2 to 13.4)	5.83 (-66666 to 66666)	8.66 (6.7 to 14.1)	12.72 (11.5 to 13.9)	8.31 (5.4 to 15.7)	7.16 (6.3 to 9.1)	9.23 (5.1 to 15.7)

Notes
[439] - PK Population
[440] - PK Population
[441] - PK Population
[442] - PK Population
[443] - PK Population
[444] - PK Population
[445] - PK Population

No statistical analyses for this end point

Secondary: Part 1: T1/2 of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 1: T1/2 of GSK3529246 (active metabolite) following repeat dose administration ^[446]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 66666 indicates full range could not be calculated due to single participant.

End point type

Secondary

End point timeframe

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[446] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[447]	1 ^[448]	9 ^[449]	2 ^[450]	6 ^[451]	4 ^[452]	8 ^[453]
Units: Hour
median (full range (min-max))	8.24 (7.7 to 10.0)	6.19 (-66666 to 66666)	7.97 (5.7 to 12.4)	7.39 (7.3 to 7.5)	8.00 (5.8 to 10.5)	6.72 (4.0 to 8.7)	11.77 (6.9 to 23.8)

Notes
[447] - PK Population
[448] - PK Population
[449] - PK Population
[450] - PK Population
[451] - PK Population
[452] - PK Population
[453] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Time invariance (RS) of GSK3529246 (active metabolite)

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End point title

Part 1: Time invariance (RS) of GSK3529246 (active metabolite) ^[454]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[454] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[455]	1 ^[456]	8 ^[457]	1 ^[458]	6 ^[459]	4 ^[460]	6 ^[461]
Units: Ratio
geometric mean (geometric coefficient of variation)	0.92 ( 25.58 )	0.96 ( 99999 )	1.18 ( 32.33 )	0.63 ( 99999 )	1.20 ( 13.74 )	1.06 ( 9.48 )	1.87 ( 57.15 )

Notes
[455] - PK Population
[456] - PK Population
[457] - PK Population
[458] - PK Population
[459] - PK Population
[460] - PK Population
[461] - PK Population

No statistical analyses for this end point

Secondary: Part 1: Accumulation ratio (RO) of GSK3529246 (active metabolite)

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End point title

Part 1: Accumulation ratio (RO) of GSK3529246 (active metabolite) ^[462]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5mg QD, 10mg QD, 20mg QD, 40mg QD, 60mg QD AML, 80mg QD, 80mg QD AML, 120mg QD AML. 99999 indicates that, geometric coefficient of variation could not be calculated for single participant

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Notes
[462] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 1: GSK525762 30 mg QD MM	Part 1: GSK525762 40 mg QD MM	Part 1: GSK525762 60 mg QD NHL	Part 1: GSK525762 60 mg QD MM	Part 1: GSK525762 75 mg QD AML	Part 1: GSK525762 80 mg QD NHL	Part 1: GSK525762 100 mg QD AML
Number of subjects analysed	4 ^[463]	1 ^[464]	9 ^[465]	1 ^[466]	7 ^[467]	4 ^[468]	9 ^[469]
Units: Ratio
geometric mean (geometric coefficient of variation)	1.18 ( 25.71 )	1.02 ( 99999 )	1.61 ( 31.61 )	0.90 ( 99999 )	1.56 ( 26.04 )	1.20 ( 11.50 )	3.22 ( 59.05 )

Notes
[463] - PK Population
[464] - PK Population
[465] - PK Population
[466] - PK Population
[467] - PK Population
[468] - PK Population
[469] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent clearance (CL/F) of GSK3529246 (active metabolite) following single dose administration

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End point title

Part 2: Apparent clearance (CL/F) of GSK3529246 (active metabolite) following single dose administration ^[470]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N” of 75 mg arm within this outcome measure is greater than overall “N” for 75 mg QD MDS & N=0 for 80 mg QD CTCL.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.5 – 2 hours, 4 – 8 hours post-dose

Notes
[470] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[471]	17 ^[472]
Units: Liters per hour
arithmetic mean (standard deviation)	16.5 ( 7.71 )	15.8 ( 6.97 )

Notes
[471] - PK Population
[472] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent clearance (CL/F) of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 2: Apparent clearance (CL/F) of GSK3529246 (active metabolite) following repeat dose administration ^[473]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N=0” for 80 mg QD arm within this outcome measure.

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.5 – 2 hours, 4 – 8 hours post-dose

Notes
[473] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[474]	8 ^[475]
Units: Liters per hour
arithmetic mean (standard deviation)	15.9 ( 7.26 )	14.6 ( 8.07 )

Notes
[474] - PK Population
[475] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK3529246 (active metabolite) following single dose administration

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End point title

Part 2: Apparent central volume of distribution (V1/F) of GSK3529246 (active metabolite) following single dose administration ^[476]

End point description

End point type

Secondary

End point timeframe

Week 1 Day 1: pre-dose and at 0.5 – 2 hours, 4 – 8 hours post-dose

Notes
[476] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[477]	17 ^[478]
Units: Liters
arithmetic mean (standard deviation)	80.0 ( 37.1 )	71.5 ( 28.4 )

Notes
[477] - PK Population
[478] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK3529246 (active metabolite) following repeat dose administration

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End point title

Part 2: Apparent central volume of distribution (V1/F) of GSK3529246 (active metabolite) following repeat dose administration ^[479]

End point description

Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to “N=0” for 80 mg QD arm within this outcome measure.

End point type

Secondary

End point timeframe

Week 3 Day 1: pre-dose and at 0.5 – 2 hours, 4 – 8 hours post-dose

Notes
[479] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	7 ^[480]	8 ^[481]
Units: Liters
arithmetic mean (standard deviation)	80.0 ( 37.1 )	63.4 ( 30.6 )

Notes
[480] - PK Population
[481] - PK Population

No statistical analyses for this end point

Secondary: Part 2: Change from Baseline in Skindex-29 domain scores (emotional, functioning and symptoms score) for CTCL cohort

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End point title

Part 2: Change from Baseline in Skindex-29 domain scores (emotional, functioning and symptoms score) for CTCL cohort ^[482]

End point description

Effects of treatment on disease-related symptoms/quality of life was assessed using Skindex-29 Questionnaire,which inquires,how often(Never,Rarely,Sometime,Often,All time)during previous 4weeks parti experienced effect described in each 29 items divided in 3domains:Emotional(10 items),Symptoms(7 items),Functioning(12items).Responses to each item are transformed to linear scale of100,varying from 0(noeffect)to100(effect experienced alltime).Skindex-29 scores were reported as 3 individual domain scale scores;scale score is mean of participant’s response to items in given domain.Each domain score ranges from 0(no effect) to100(effect experienced all time),higher score implies higher impact of skin disease.Baseline was most recent non-missing value prior to/on first study treatment dose date.Change from Baseline is postdose visit value-Baseline.Only those parti with data avail at specified points were analyzed(n=X).88888(SD couldnot calculated for single parti).77777(data notavailable)

End point type

Secondary

End point timeframe

Baseline (pre-dose Week1 Day1) and Week 3, Week 7, Week 10, Week 16 and Week 24

Notes
[482] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[483]	1 ^[484]
Units: Scores on a scale
arithmetic mean (standard deviation)
Emotional score, Week 3, n=6,1	-5.83 ( 15.221 )	9.17 ( 88888 )
Emotional score, Week 7, n=5,0	-19.50 ( 22.735 )	77777 ( 77777 )
Emotional score, Week 10, n=3,0	-44.17 ( 26.497 )	77777 ( 77777 )
Emotional score, Week 16, n=3,0	-10.00 ( 10.897 )	77777 ( 77777 )
Emotional score, Week 24, n=2,0	-18.75 ( 1.768 )	77777 ( 77777 )
Functioning score, Week 3, n=6,1	-1.42 ( 7.742 )	30.87 ( 88888 )
Functioning score, Week 7, n=5,0	-13.37 ( 23.000 )	77777 ( 77777 )
Functioning score, Week 10, n=3,0	-35.67 ( 27.820 )	77777 ( 77777 )
Functioning score, Week 16, n=3,0	-13.45 ( 9.788 )	77777 ( 77777 )
Functioning score, Week 24, n=2,0	-18.84 ( 11.919 )	77777 ( 77777 )
Symptoms score, Week 3, n=6,1	6.55 ( 24.055 )	12.50 ( 88888 )
Symptoms score, Week 7, n=5,0	-2.14 ( 18.489 )	77777 ( 77777 )
Symptoms score, Week 10, n=3,0	-29.76 ( 20.927 )	77777 ( 77777 )
Symptoms score, Week 16, n=3,0	-8.33 ( 19.670 )	77777 ( 77777 )
Symptoms score, Week 24, n=2,0	-14.29 ( 10.102 )	77777 ( 77777 )

Notes
[483] - All Treated Population
[484] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with non-serious AEs and SAEs and AELDs

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End point title

Part 2: Number of participants with non-serious AEs and SAEs and AELDs ^[485]

End point description

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[485] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[486]	16 ^[487]	1 ^[488]
Units: Participants
Non-serious AEs	7	16	1
SAEs	5	12	1
AELD	0	9	0

Notes
[486] - All Treated Population
[487] - All Treated Population
[488] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with dose reductions

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End point title

Part 2: Number of participants with dose reductions ^[489]

End point description

Number of participants with dose reductions due to any reason is presented.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[489] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[490]	16 ^[491]	1 ^[492]
Units: Participants	6	7	0

Notes
[490] - All Treated Population
[491] - All Treated Population
[492] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with dose interruptions/delays

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End point title

Part 2: Number of participants with dose interruptions/delays ^[493]

End point description

Number of participants with any dose interruptions or delays is presented.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[493] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[494]	16 ^[495]	1 ^[496]
Units: Participants	7	13	1

Notes
[494] - All Treated Population
[495] - All Treated Population
[496] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with grade change from Baseline in clinical chemistry parameters

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End point title

Part 2: Number of participants with grade change from Baseline in clinical chemistry parameters ^[497]

End point description

Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, Prothrombin international normalized ratio (Pro. INR), albumin, amylase, ALT, AST, bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, Triglycerides, ALP. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). 77777 indicates data is not available.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[497] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[498]	16 ^[499]	1 ^[500]
Units: Participants
Glucose, n=7,16,1	6	14	1
Pro.INR, n=4,13,0	2	5	77777
Albumin, n=7,16,1	1	9	1
ALT, n=7,16,1	4	4	0
Amylase, n=7,15,1	3	1	1
AST, n=7,15,1	3	6	1
Bilirubin, n=7,16,1	3	10	0
Calcium, n=7,16,1	1	2	1
Calcium Ionized, n=7,16,1	2	9	0
Cholesterol, n=7,15,1	2	1	0
Creatine Kinase, n=5,11,1	1	1	0
Creatinine, n=7,16,1	0	4	0
Lipase, n=7,13,1	2	2	1
Magnesium, n=7,16,1	2	7	0
Sodium, n=7,16,1	4	6	1
Triglycerides, n=7,15,1	7	6	0
ALP, n=7,16,1	2	1	0

Notes
[498] - All Treated Population
[499] - All Treated Population
[500] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with grade change from Baseline in hematology parameters

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End point title

Part 2: Number of participants with grade change from Baseline in hematology parameters ^[501]

End point description

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[501] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[502]	16 ^[503]	1 ^[504]
Units: Participants
Hemoglobin	4	8	1
Lymphocytes	4	8	1
Neutrophils	2	7	0
Platelets	5	9	1
Leukocytes	1	6	0

Notes
[502] - All Treated Population
[503] - All Treated Population
[504] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method

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End point title

Part 2: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method ^[505]

End point description

Urine samples were collected to assess glucose, ketones, occult blood, urine protein. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented. Only those participants with data available at the specified data points were analyzed represented by n=X in category titles).

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[505] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[506]	12 ^[507]	1 ^[508]
Units: Participants
Glucose, n=5,12,1	4	3	0
Ketones, n=7,12,1	1	0	0
Occult blood, n=7,8,1	2	2	0
Protein, n=6,11,1	0	7	0

Notes
[506] - All Treated Population
[507] - All Treated Population
[508] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature

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End point title

Part 2: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature ^[509]

End point description

Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low <60 beats per minute [bpm] and high >100 bpm); For body temperature (<=35 degrees Celsius or >=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[509] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[510]	16 ^[511]	1 ^[512]
Units: Participants
Pulse rate, To Low	2	0	0
Pulse rate, To Normal or No change	3	9	0
Pulse Rate, To High	3	7	1
Temperature, To Low	1	0	0
Temperature, To Normal or No Change	5	13	1
Temperature, To High	1	3	0

Notes
[510] - All Treated Population
[511] - All Treated Population
[512] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with increase to Grade 3 from Baseline in vital signs: DBP and SBP

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End point title

Part 2: Number of participants with increase to Grade 3 from Baseline in vital signs: DBP and SBP ^[513]

End point description

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[513] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[514]	16 ^[515]	1 ^[516]
Units: Participants
DBP	0	0	0
SBP	3	1	1

Notes
[514] - All Treated Population
[515] - All Treated Population
[516] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading)

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End point title

Part 2: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading) ^[517]

End point description

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[517] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[518]	16 ^[519]	1 ^[520]
Units: Participants
Abnormal-Clinically significant	0	1	0
Abnormal-Not Clinically significant	6	11	1

Notes
[518] - All Treated Population
[519] - All Treated Population
[520] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Progression free survival (PFS)

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End point title

Part 2: Progression free survival (PFS) ^[521]

End point description

PFS is interval of time(in months)between date of first dose &earlier of date of disease progression &date of death due to any cause. Progression is participants(pt’s)with MDS &with<5% blasts:>=50% increase in blastto>5% blasts/pt’s with 5-10% blasts:>=50% increase to >10% blast pt’s with 10-20% blast:>=50%increase to >20% blast, pt’s with 20%-30% blast:>=50% increase to>30% blast, For CTCL:>=25% increase in skin disease from Baseline/new tumor(T3[1/more tumors(>=1cm diameter]) in pt’s with T1(Limited patches,papule&/or plaque covering<10% of skin surface;may stratify in T1a[patch only]v T1b [plaque+-patch]),T2(Patch,papule/plaque covering >=10% of skin surface;may stratify in T2a[patch only]v T2b [plaque+-patch])/T4(Confluence of erythema covering >=80% body surface area)only skin disease/loss of response in pts with CR/PR,increase of skin score of >sum of nadir +50% Baseline score.55555-median &IQR range could not be calculated.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[521] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[522]	16 ^[523]	1 ^[524]
Units: Months
median (inter-quartile range (Q1-Q3))	8.15 (3.48 to 55555)	2.00 (1.45 to 3.48)	55555 (55555 to 55555)

Notes
[522] - All Treated Population
[523] - All Treated Population
[524] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Duration of response (DOR)

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End point title

Part 2: Duration of response (DOR) ^[525]

End point description

Duration of response is defined as the time from the first documented evidence response (CR or PR lasting 4 months for CTCL; and CR, marrow CR, CRp, Cri or PR for MDS) until the first documented disease progression or death due to any cause. Median and inter-quartile range (first quartile and third quartile) of duration of response are presented. Only those participants with data available at the specified data points were analyzed. Participants with incomplete response rates were excluded from the analysis.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[525] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 75 mg QD MDS
Number of subjects analysed	4 ^[526]
Units: Months
median (inter-quartile range (Q1-Q3))	3.29 (3.29 to 3.29)

Notes
[526] - All Treated Population

No statistical analyses for this end point

Secondary: Part 2: Overall survival (OS)

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End point title

Part 2: Overall survival (OS) ^[527]

End point description

OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented. 55555 indicates median and inter-quartile range could not be calculated.

End point type

Secondary

End point timeframe

Up to 36.4 weeks

Notes
[527] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	Part 2: GSK525762 60 mg QD CTCL	Part 2: GSK525762 75 mg QD MDS	Part 2: GSK525762 80 mg QD CTCL
Number of subjects analysed	7 ^[528]	16 ^[529]	1 ^[530]
Units: Months
median (inter-quartile range (Q1-Q3))	55555 (55555 to 55555)	5.85 (1.46 to 16.10)	55555 (55555 to 55555)

Notes
[528] - All Treated Population
[529] - All Treated Population
[530] - All Treated Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality, non-serious and serious adverse events were collected from the start of study treatment until 28 days following discontinuation of study treatment (up to 86.9 weeks for Part 1 and up to 36.4 weeks for Part 2)

Adverse event reporting additional description

All-cause mortality, non-serious and serious adverse events were collected in All Treated population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

GSK525762 5 MG QD

Reporting group description

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

Reporting group title

GSK525762 10 MG QD

Reporting group description

Participants were administered once daily oral dose of 10 mg GSK525762.

Reporting group title

GSK525762 20 MG QD

Reporting group description

Participants were administered once daily oral dose of 20 mg GSK525762.

Reporting group title

GSK525762 30 MG QD MM

Reporting group description

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

Reporting group title

GSK525762 40 MG QD

Reporting group description

Participants were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

GSK525762 40 MG QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 40 mg GSK525762.

Reporting group title

GSK525762 60 MG QD AML

Reporting group description

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

GSK525762 60 MG QD NHL

Reporting group description

Participants with Non-Hodgkin’s Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

GSK525762 60 MG QD MM

Reporting group description

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

GSK525762 75 MG QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

GSK525762 80 MG QD

Reporting group description

Participants were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

GSK525762 80 MG QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

GSK525762 80 MG QD NHL

Reporting group description

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

Reporting group title

GSK525762 100 MG QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

Reporting group title

GSK525762 120 MG QD AML

Reporting group description

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

Reporting group title

GSK525762 60 MG QD CTCL

Reporting group description

Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762.

Reporting group title

GSK525762 75 MG QD MDS

Reporting group description

Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762.

Reporting group title

GSK525762 80 MG QD CTCL

Reporting group description

Participants CTCL were administered once daily oral dose of 80 mg GSK525762.

GSK525762 5 MG QD

GSK525762 10 MG QD

GSK525762 20 MG QD

GSK525762 30 MG QD MM

GSK525762 40 MG QD

GSK525762 40 MG QD MM

GSK525762 60 MG QD AML

GSK525762 60 MG QD NHL

GSK525762 60 MG QD MM

GSK525762 75 MG QD AML

GSK525762 80 MG QD

GSK525762 80 MG QD AML

GSK525762 80 MG QD NHL

GSK525762 100 MG QD AML

GSK525762 120 MG QD AML

GSK525762 60 MG QD CTCL

GSK525762 75 MG QD MDS

GSK525762 80 MG QD CTCL

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 1 (100.00%)

0 / 1 (0.00%)

4 / 5 (80.00%)

0 / 1 (0.00%)

3 / 4 (75.00%)

6 / 8 (75.00%)

12 / 18 (66.67%)

2 / 3 (66.67%)

8 / 8 (100.00%)

1 / 1 (100.00%)

6 / 7 (85.71%)

7 / 7 (100.00%)

14 / 16 (87.50%)

6 / 6 (100.00%)

5 / 7 (71.43%)

12 / 16 (75.00%)

1 / 1 (100.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cancer pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chloroma

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour haemorrhage

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypotension

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

1 / 8 (12.50%)

2 / 18 (11.11%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

1 / 2

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Asthenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chest pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mucosal inflammation

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oedema peripheral

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Performance status decreased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Anaphylactic reaction

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Respiratory failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

1 / 3 (33.33%)

1 / 8 (12.50%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

2 / 16 (12.50%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Epistaxis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemothorax

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Amylase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatinine increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ejection fraction decreased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcus test positive

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Troponin I increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

White blood cell count increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Rib fracture

subjects affected / exposed

0 / 1 (0.00%)

2 / 5 (40.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Fall

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Humerus fracture

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Road traffic accident

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transfusion reaction

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper limb fracture

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Cardiac failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Supraventricular tachycardia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Haemorrhage intracranial

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperammonaemic encephalopathy

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intracranial haematoma

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Thrombocytopenia

subjects affected / exposed

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

8 / 18 (44.44%)

1 / 3 (33.33%)

3 / 8 (37.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

5 / 7 (71.43%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

4 / 16 (25.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

8 / 9

2 / 2

3 / 3

0 / 0

5 / 5

0 / 0

4 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

2 / 8 (25.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

3 / 7 (42.86%)

0 / 7 (0.00%)

2 / 16 (12.50%)

3 / 6 (50.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

0 / 0

0 / 2

0 / 0

0 / 3

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

2 / 8 (25.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leukocytosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

2 / 8 (25.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Anaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Chalazion

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Diarrhoea

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

1 / 16 (6.25%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 1 (100.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gingival hypertrophy

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestine perforation

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Proctalgia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal haemorrhage

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Vomiting

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholecystitis acute

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

2 / 16 (12.50%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Haematuria

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal colic

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bone pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal chest pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Pneumonia

subjects affected / exposed

1 / 1 (100.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

1 / 1 (100.00%)

3 / 7 (42.86%)

2 / 7 (28.57%)

5 / 16 (31.25%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 5

0 / 2

1 / 11

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

Sepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

4 / 16 (25.00%)

2 / 6 (33.33%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 2

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 4

0 / 0

Neutropenic sepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

2 / 16 (12.50%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacterial sepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis infective

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile colitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Folliculitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Genital infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes simplex reactivation

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes zoster

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Mucormycosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteomyelitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Varicella zoster virus infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular device infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

2 / 16 (12.50%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypophosphataemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 16 (6.25%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertriglyceridaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Starvation ketoacidosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour lysis syndrome

subjects affected / exposed

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 16 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	GSK525762 5 MG QD	GSK525762 10 MG QD	GSK525762 20 MG QD	GSK525762 30 MG QD MM	GSK525762 40 MG QD	GSK525762 40 MG QD MM	GSK525762 60 MG QD AML	GSK525762 60 MG QD NHL	GSK525762 60 MG QD MM	GSK525762 75 MG QD AML	GSK525762 80 MG QD	GSK525762 80 MG QD AML	GSK525762 80 MG QD NHL	GSK525762 100 MG QD AML	GSK525762 120 MG QD AML	GSK525762 60 MG QD CTCL	GSK525762 75 MG QD MDS	GSK525762 80 MG QD CTCL
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 1 (100.00%)	1 / 1 (100.00%)	1 / 1 (100.00%)	5 / 5 (100.00%)	1 / 1 (100.00%)	4 / 4 (100.00%)	8 / 8 (100.00%)	18 / 18 (100.00%)	3 / 3 (100.00%)	8 / 8 (100.00%)	1 / 1 (100.00%)	7 / 7 (100.00%)	7 / 7 (100.00%)	16 / 16 (100.00%)	6 / 6 (100.00%)	7 / 7 (100.00%)	16 / 16 (100.00%)	1 / 1 (100.00%)
Vascular disorders
Hypotension
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	1	1	0	0	1	1	0	0	1	0	0	2	0
Hypertension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	1 / 1 (100.00%)	3 / 7 (42.86%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	1	3	0	0	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	6 / 18 (33.33%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 1 (0.00%)	3 / 7 (42.86%)	3 / 7 (42.86%)	4 / 16 (25.00%)	1 / 6 (16.67%)	4 / 7 (57.14%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0	0	1	6	1	1	0	3	3	4	1	4	1	0
Pyrexia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	3 / 18 (16.67%)	2 / 3 (66.67%)	1 / 8 (12.50%)	0 / 1 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	3 / 16 (18.75%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	2	0	1	0	5	2	2	0	2	1	3	2	0	0	0
Asthenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 3 (0.00%)	3 / 8 (37.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	1	3	0	3	0	0	2	0	0	1	1	1
Oedema peripheral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	2 / 6 (33.33%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	1	3	0	2	0	0	0	2	2	1	1	0
Mucosal inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	2	1	2	0	0	0	0
Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0	1	1	0	0	0	0	0	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	1 / 18 (5.56%)	1 / 3 (33.33%)	2 / 8 (25.00%)	0 / 1 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	3 / 16 (18.75%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 16 (12.50%)	1 / 1 (100.00%)
occurrences all number	0	0	0	1	1	0	2	1	1	2	0	2	1	4	0	1	2	1
Epistaxis
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 1 (0.00%)	3 / 7 (42.86%)	1 / 7 (14.29%)	2 / 16 (12.50%)	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0	0	1	2	1	0	0	4	1	2	2	0	2	0
Dyspnoea
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	2 / 18 (11.11%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	1	0	1	0	0	2	2	1	1	0	1	1	2	0	0	2	0
Oropharyngeal pain
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	1	0	1	2	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 16 (6.25%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	1	0	1	2	0	0	0
Investigations
Blood bilirubin increased
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	3 / 18 (16.67%)	0 / 3 (0.00%)	4 / 8 (50.00%)	1 / 1 (100.00%)	3 / 7 (42.86%)	0 / 7 (0.00%)	11 / 16 (68.75%)	3 / 6 (50.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	4	4	0	4	1	3	0	11	3	0	3	0
International normalised ratio increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	2 / 18 (11.11%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	8 / 16 (50.00%)	3 / 6 (50.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	4	2	0	2	0	1	0	10	3	0	0	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	5 / 18 (27.78%)	0 / 3 (0.00%)	1 / 8 (12.50%)	1 / 1 (100.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	4 / 16 (25.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	5	0	1	1	1	0	4	2	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 18 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	1	0	0	0	0	2	1	0	2	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	1	0	0	1	1	0	2	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Weight decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Nervous system disorders
Dysgeusia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	2 / 18 (11.11%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 1 (0.00%)	3 / 7 (42.86%)	1 / 7 (14.29%)	6 / 16 (37.50%)	1 / 6 (16.67%)	3 / 7 (42.86%)	6 / 16 (37.50%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	3	2	0	2	0	3	1	6	1	4	6	1
Dizziness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	3 / 16 (18.75%)	1 / 6 (16.67%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	1	0	0	1	3	1	0	3	0
Headache
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Taste disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Anxiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	3 / 4 (75.00%)	0 / 8 (0.00%)	8 / 18 (44.44%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	3 / 7 (42.86%)	1 / 16 (6.25%)	0 / 6 (0.00%)	3 / 7 (42.86%)	1 / 16 (6.25%)	1 / 1 (100.00%)
occurrences all number	0	0	0	1	0	3	0	8	1	0	0	0	3	1	0	5	1	2
Anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	6 / 18 (33.33%)	1 / 3 (33.33%)	2 / 8 (25.00%)	1 / 1 (100.00%)	1 / 7 (14.29%)	3 / 7 (42.86%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	1 / 1 (100.00%)
occurrences all number	0	0	0	1	0	1	0	6	1	2	1	1	4	2	0	0	2	2
Febrile neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0	1	0	0	0	2	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	3 / 18 (16.67%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	5	0	4	0	0	0	0	0	0	0	0	0	0
Coagulopathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	2	1	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	1 / 1 (100.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	7 / 18 (38.89%)	0 / 3 (0.00%)	4 / 8 (50.00%)	1 / 1 (100.00%)	4 / 7 (57.14%)	3 / 7 (42.86%)	11 / 16 (68.75%)	3 / 6 (50.00%)	2 / 7 (28.57%)	11 / 16 (68.75%)	0 / 1 (0.00%)
occurrences all number	2	0	0	2	2	2	6	8	0	4	2	6	3	15	3	2	14	0
Nausea
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	6 / 18 (33.33%)	2 / 3 (66.67%)	4 / 8 (50.00%)	0 / 1 (0.00%)	6 / 7 (85.71%)	2 / 7 (28.57%)	8 / 16 (50.00%)	3 / 6 (50.00%)	2 / 7 (28.57%)	11 / 16 (68.75%)	0 / 1 (0.00%)
occurrences all number	2	0	0	2	0	1	4	7	2	4	0	6	2	10	4	2	12	0
Vomiting
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 18 (16.67%)	2 / 3 (66.67%)	0 / 8 (0.00%)	1 / 1 (100.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	4 / 16 (25.00%)	1 / 6 (16.67%)	2 / 7 (28.57%)	7 / 16 (43.75%)	0 / 1 (0.00%)
occurrences all number	0	0	2	0	0	0	1	3	3	0	1	2	1	4	1	2	8	0
Abdominal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	3 / 18 (16.67%)	2 / 3 (66.67%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)	0 / 7 (0.00%)	4 / 16 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	4	2	1	0	1	0	3	1	0	5	0
Constipation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	2 / 18 (11.11%)	1 / 3 (33.33%)	1 / 8 (12.50%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	2	2	1	1	1	0	0	3	0	1	1	0
Dry mouth
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	3 / 18 (16.67%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	1	3	0	0	0	0	0	0	0	2	1	0
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	3 / 8 (37.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	3	0	0	2	0	0	0	4	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 18 (16.67%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	1	3	0	1	0	1	2	2	0	0	3	0
Pruritus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	3	1	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	1	1	0	1	0	1	0	0	3	0
Muscle spasms
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	2 / 18 (11.11%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	2	2	1	0	0	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	1	0	2	0	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	1	0	0	1	0	1	1	0	3	0
Oral herpes
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Upper respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	1	0	0	1	0	1	0	0	1	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	0	0	0	0	0	0	1	1	0
Oral candidiasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	4 / 7 (57.14%)	7 / 16 (43.75%)	3 / 6 (50.00%)	2 / 7 (28.57%)	3 / 16 (18.75%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	1	1	0	2	0	1	8	7	3	2	3	0
Decreased appetite
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	2 / 8 (25.00%)	3 / 18 (16.67%)	2 / 3 (66.67%)	3 / 8 (37.50%)	0 / 1 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	3 / 16 (18.75%)	1 / 6 (16.67%)	2 / 7 (28.57%)	4 / 16 (25.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	2	3	2	3	0	2	1	3	1	2	4	0
Hypokalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	1 / 18 (5.56%)	1 / 3 (33.33%)	2 / 8 (25.00%)	1 / 1 (100.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	4 / 16 (25.00%)	3 / 6 (50.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	3	1	1	2	3	1	0	6	3	0	3	0
Hypomagnesaemia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	1 / 3 (33.33%)	1 / 8 (12.50%)	1 / 1 (100.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 1 (0.00%)
occurrences all number	1	0	0	1	0	0	1	1	1	1	1	1	0	2	0	0	2	0
Hyponatraemia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 3 (0.00%)	1 / 8 (12.50%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	2	0	0	1	0	0	1	1	0	1	1	0	0	2	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 3 (0.00%)	2 / 8 (25.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	1	0	0	1	1	0	2	2	0	0	0	0	0	0	0
Hypophosphataemia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	1	0	0	2	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Aug 2013

Amendment 1: The study duration has been modified at the request of the Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom. MHRA requested the removal of “until commercial supply of GSK525762 becomes available” as a duration of exposure in accordance with the Commission Directive 2005/28/EC. In addition, the sponsor/medical monitor information page has updated information.

15 Oct 2013

Amendment 2: At the request of the Food and Drug Administration (FDA), United States, the dose limiting toxicity (DLT) was updated to require that it must clearly be established that an event is unrelated to treatment for the event to not be considered a DLT; the stopping rules related to safety were expanded. Additional changes include the clarification of exploratory endpoints to assess metabolites, correction of exclusion criteria and clarification of the Time and Events Table, Dietary Restrictions, and the futility analysis of Part 2.

12 Nov 2014

Amendment 3: The secondary objectives of Part 1 were updated to include evaluation of the clinical activity of GSK525762 (response rate and overall survival). Additional details of twice daily (BID) dosing during dose escalation were included. Eligibility criteria refined: 1) Clarification of eligibility for participants with Acute Myeloid Leukemia (AML) (Part 1 and 2). Platelets count eligibility criteria were specified for each group of hematological malignancies separately. 3) Exemption of exclusion due to prior allogeneic stem cell transplant added. DLT for hematological toxicities clarified and dose reduction algorithm for thrombocytopenia added. Study statistic amended for part 2 (AML expansion cohort): hypothesis and number of participants. Data from ongoing preclinical and clinical research added. Time point of collection for samples for disease and efficacy assessments refined. List of baseline assessments for each indication added. Minor clarifications, reformatting of tables and typographical errors are also addressed in this amendment.

06 Apr 2015

Amendment 4: An update to the corrected QT(QTc) management guidelines and enhanced guidance for management and dose modifications for thrombocytopenia, specifically for participants with AML, has been added. Separation of cohorts in Part 1 was included to determine Maximum tolerated dose (MTD)/ Recommended Part 2 Dose (RP2D) separately in AML, Multiple Myeloma (MM), Non-Hodgkin’s Lymphoma (NHL) cohorts. Eligibility criteria were refined to account for new platelet management guidelines. Eligibility regarding prior allogeneic stem cell transplant and central nervous system (CNS) disease were simplified. Inclusion of dose expansion cohorts for MM and NHL has been added in Part 2. PD assessments have been removed from Part 2 and tumor biopsies were added in Part 2 for translational research. The 100 milligrams (mg) dose strength was removed due to a change in manufacturing. Minor clarifications, reformatting of tables and typographical errors were also addressed in this amendment.

08 Jul 2015

Amendment 5: Updated inclusion criteria and guidance on contraception use based on emerging data from preclinical studies of embryo-fetal development. Minor clarifications were made regarding the Echo and Holter monitoring requirements and the list of medications with risk for Torsades de Pointes and prohibited medications were updated. The AML response criteria were updated with modified Cheson 2003 guidelines. Futhermore, the dosing schedule was updated to a continuous daily dosing schedule. Finally, after an internal QTc analysis and evaluation of cardiac safety data collected from all participants in the BET115521 (NCT01587703) study up to and including the 100mg Once daily (QD) cohort available by 15-May-2015, the 48-hour telemetry requirement has been removed for all parts of the study and the frequency of Holter Monitoring was decreased in Part 1. Minor clarifications, reformatting of tables and typographical errors were also addressed in this amendment.

15 Mar 2016

Amendment 6: Updated Visit Windows to provide additional clarification on clinical visits. Updated GSK525762 Investigational Product Dosage/Administration to include both amorphous free base and crystalline besylate formulations of GSK525762 in the study. Updated Meals and Dietary Restrictions to include the meals and dietary requirements for the new besylate formulation included in the study. Minor clarifications, reformatting of tables and typographical errors were also addressed in this amendment.

23 Jun 2016

Amendment 7: Study design was amended to include collection of additional safety data of GSK525762 twice dail (BID) dosing (exploratory cohort) after determination of maximum tolerated dose with QD dose and to evaluate the preliminary efficacy of GSK525762 BID dosing. The secondary objectives of Part 1 were updated to include evaluation of clinical efficacy of GSK525762 (overall response rate). The endpoints for secondary objective of Part 2 (determination of clinical activity of GSK525762) was updated to include Time to Preograssion (TTP), Duration of Response (DOR), progression Free Survival (PFS) for MM and NHL. Eligibility criteria were clarified specifying hematologic malignancies (AML, MM, NHL) for both Part 1 and 2. Risk associated with drug interaction was updated. Permanent discontinuation from study treatment section was updated. Time and events tables were also updated in line with study design modifications. Whole section of urine collection was removed. Tables of cautionary medications, prohibited medications and drugs affecting pharmacokinetic (PK) of GSK525762 were updated. Interim analysis was included for part 1. Minor clarifications, formatting and typographical errors were also addressed in this amendment.

14 Feb 2017

Amendment 8: The study population for the AML cohort in Part 2 was amended from a population of participants with AML to a population of participants with relapsed or refractory myelodysplastic syndrome (MDS) or hypoproliferative AML that has arisen from an antecedent MDS. The Part 2 primary and secondary objectives along with the eligibility criteria were updated to include this new population. The safety assessments were updated to be in line with the Investigator Brochure. The dose limiting toxicity criteria were modified to remove the specific criteria for leukemia. The time and events tables were updated to reduce the cardiac monitoring (ecg, holter and troponin), remove Messenger Ribonucleic acid (mRNA) and cytokine collection, add a Pain Assessment, addition of an exploratory translational research blood draw and to add Factor VII assay collection. The disease related events/outcomes section was removed and the pregnancy reporting timeframe was reduced to 24 hours. Fever was removed from the dose adjusting/stopping safety criteria. Aspirin and non-steroidal-anti-inflammatory drugs (NSAIDs) were added to the Cautionary medications. Response Criteria for Myelodysplastic Syndromes (MDS) was added as an Appendix. GlaxoSmithKline Document Number 2011N113741_03 Version 3 changed to GlaxoSmithKline Document Number 2011N113741_05 Version 5 throughout the document. Table numbers were updated. Figure numbers are updated throughout the document. Minor clarifications, formatting and typographical errors were also addressed in this amendment.

15 Mar 2018

Amendment 9: The study population for the NHL cohort in Part 2 was amended from a population of participants with NHL to a population of participants with cutaneous T-cell lymphoma (CTCL). The Part 2 primary and secondary objectives along with the eligibility criteria were updated to include this new CTCL population, and removal of expansion into multiple myeloma in Part 2. Eligibility criteria for all populations were updated (ECOG, cardiac safety). The time and events tables were updated to reduce the cardiac monitoring based on updated risk/benefit profile, and BID dosing was removed. Medications affecting QT prolongation were re-categorized from prohibited to cautionary. Liver chemistry monitoring, interruption stopping and follow-up criteria were updated as per latest criteria. Response Criteria for CTCL was added as an Appendix, and a QOL questionnaire (SKINDEX-29) was added. Minor clarifications, formatting and typographical errors were also addressed in this amendment.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed, refractory hematologic malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Number of participants with non-serious adverse events (AEs) and serious adverse events (SAEs) and AE leading to discontinuation (AELD)

Primary: Part 1: Number of participants with non-serious adverse events (AEs) and serious adverse events (SAEs) and AE leading to discontinuation (AELD)

Primary: Part 1: Number of participants with Dose Limiting Toxicities (DLTs)

Primary: Part 1: Number of participants with Dose Limiting Toxicities (DLTs)

Primary: Part 1: Number of participants with dose reductions

Primary: Part 1: Number of participants with dose reductions

Primary: Part 1: Number of participants with any dose interruptions or delays

Primary: Part 1: Number of participants with any dose interruptions or delays

Primary: Part 1: Number of participants with grade change from Baseline in clinical chemistry parameters

Primary: Part 1: Number of participants with grade change from Baseline in clinical chemistry parameters

Primary: Part 1: Number of participants with grade change from Baseline in hematology parameters

Primary: Part 1: Number of participants with grade change from Baseline in hematology parameters

Primary: Part 1: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method

Primary: Part 1: Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick method

Primary: Part 1: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature

Primary: Part 1: Number of participants with worst case vital signs results relative to Baseline: Pulse rate and body temperature

Primary: Part 1: Number of participants with increase to Grade 3 from Baseline in vital signs: Diastolic Blood pressure (DBP) and Systolic Blood pressure (SBP)

Primary: Part 1: Number of participants with increase to Grade 3 from Baseline in vital signs: Diastolic Blood pressure (DBP) and Systolic Blood pressure (SBP)

Primary: Part 1: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading)

Primary: Part 1: Number of participants with worst-case post-Baseline abnormal electrocardiogram (ECG) findings (investigator reading)

Primary: Part 2: Objective response rate (ORR) (MDS cohort)

Primary: Part 2: Objective response rate (ORR) (MDS cohort)

Primary: Part 2: Objective response rate lasting at least 4 months (ORR4) (CTCL cohorts)

Primary: Part 2: Objective response rate lasting at least 4 months (ORR4) (CTCL cohorts)

Secondary: Part 1: Overall response rate (ORR)- Investigator assessment

Secondary: Part 1: Overall response rate (ORR)- Investigator assessment

Secondary: Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 following single dose administration

Secondary: Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 following single dose administration

Secondary: Part 1: AUC(0-24) and Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK525762 following repeat dose administration

Secondary: Part 1: AUC(0-24) and Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK525762 following repeat dose administration

Secondary: Part 1: Maximum Observed Concentration (Cmax) and Minimum plasma concentration (Cmin) of GSK525762 following single dose administration

Secondary: Part 1: Maximum Observed Concentration (Cmax) and Minimum plasma concentration (Cmin) of GSK525762 following single dose administration

Secondary: Part 1: Cmax and Cmin of GSK525762 following repeat dose administration

Secondary: Part 1: Cmax and Cmin of GSK525762 following repeat dose administration

Secondary: Part 1: Trough concentration (Ctau) of GSK525762 following repeat dose administration

Secondary: Part 1: Trough concentration (Ctau) of GSK525762 following repeat dose administration

Secondary: Part 1: Time of maximum concentration (Tmax) of GSK525762 following single dose administration

Secondary: Part 1: Time of maximum concentration (Tmax) of GSK525762 following single dose administration

Secondary: Part 1: Tmax of GSK525762 following repeat dose administration

Secondary: Part 1: Tmax of GSK525762 following repeat dose administration

Secondary: Part 1: Terminal half life (T1/2) of GSK525762 following single dose administration

Secondary: Part 1: Terminal half life (T1/2) of GSK525762 following single dose administration

Secondary: Part 1: T1/2 of GSK525762 following repeat dose administration

Secondary: Part 1: T1/2 of GSK525762 following repeat dose administration

Secondary: Part 1: Time invariance (RS) of GSK525762

Secondary: Part 1: Time invariance (RS) of GSK525762

Secondary: Part 1: Accumulation ratio (RO) of GSK525762

Secondary: Part 1: Accumulation ratio (RO) of GSK525762

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after single dose administration

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after single dose administration

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after repeat dose administration

Secondary: Part 2: Apparent clearance (CL/F) of GSK525762 after repeat dose administration

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following single dose administration

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following single dose administration

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following repeat dose administration

Secondary: Part 2: Apparent central volume of distribution (V1/F) of GSK525762 following repeat dose administration

Secondary: Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Cmax and Cmin of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Trough concentration (Ctau) of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Trough concentration (Ctau) of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following single dose administration

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following repeat dose administration

Secondary: Part 1: Tmax of GSK3529246 (active metabolite) following repeat dose administration

Clinical Trial Results:
A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed, refractory hematologic malignancies