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Clinical Trial Results:
A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Summary
EudraCT number	2017-000861-58
Trial protocol	GB IT
Global end of trial date	03 Jun 2020

Results information
Results version number	v1(current)
This version publication date	11 Mar 2021
First version publication date	11 Mar 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

NP39761

ISRCTN number

US NCT number

NCT03287245

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Roche Trial Infor, Hoffmann-La Roche, +41 61 6878333, global.trial_information@roche.com

Scientific contact

Medical Communications, Hoffmann-La Roche, +41 61 6878333, global.trial_information@roche.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

03 Jun 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 Mar 2020

Global end of trial reached?

Yes

Global end of trial date

03 Jun 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

This is an open-label, single-arm study of idasanutlin monotherapy in subjects with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. The initial phase will assess the safety and efficacy of idasanutlin monotherapy in ruxolitinib naïve and ruxolitinib-resistant or intolerant subjects, respectively. If the initial phase shows promising results for ruxolitinib-resistant or intolerant subjects, an expansion phase will be opened to further characterize the efficacy of idasanutlin.

Protection of trial subjects

The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) guidelines according to the regulations and procedures described in the protocol.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Sep 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Canada: 3

Country: Number of subjects enrolled

Italy: 6

Country: Number of subjects enrolled

United States: 15

Worldwide total number of subjects

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

Total of 27 subjects were enrolled and received study treatment. All 27 subjects were discontinued from study before the planned date of follow-up. The study was pre-maturely terminated by the sponsor's decision.

Screening details

A total of 48 subjects were screened for enrollment; 21 were failed screening.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ruxolitinib-naïve Subjects With Splenomegaly

Arm description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Arm type

Experimental

Investigational medicinal product name

Idasanutlin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation

Ruxolitinib-naïve Subjects Without Splenomegaly

Arm description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Arm type

Experimental

Investigational medicinal product name

Idasanutlin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation

Ruxolitinib-Resistant or Intolerant With Splenomegaly

Arm description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Arm type

Experimental

Investigational medicinal product name

iIasanutlin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation

Ruxolitinib-Resistant or Intolerant Without Splenomegaly

Arm description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Arm type

Experimental

Investigational medicinal product name

dasanutlin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation

Number of subjects in period 1	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Started	15	5	6	1
Completed	0	0	0	0
Not completed	15	5	6	1
Consent withdrawn by subject	8	3	3	-
Physician decision	3	2	-	-
Adverse event, non-fatal	1	-	-	-
Study terminated by sponsor	3	-	3	1

Baseline characteristics

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Reporting group title

Ruxolitinib-naïve Subjects With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib-naïve Subjects Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib-Resistant or Intolerant With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Reporting group title

Ruxolitinib-Resistant or Intolerant Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Reporting group values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly	Total
Number of subjects	15	5	6	1	27
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	13	5	4	1	23
From 65-84 years	2	0	2	0	4
85 years and over	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	54.5 ± 10.7	56.8 ± 8.8	60.3 ± 8.4	55 ± 0	-
Sex: Female, Male
Units:
Female	2	5	4	0	11
Male	13	0	2	1	16
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	1	0	0	0	1
Not Hispanic or Latino	14	5	6	1	26
Race/Ethnicity, Customized
Units: Subjects
Asian	1	0	0	0	1
White	14	5	6	1	26

Subject analysis set title

Ruxolitinib-Naïve Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Subject analysis set title

Ruxolitinib-Resistant or Intolerant Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Subject analysis sets values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects	20	7
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	18	5
From 65-84 years	2	2
85 years and over	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	55.1 ± 10.1	59.6 ± 7.9
Sex: Female, Male
Units:
Female	7	4
Male	13	3
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	1	0
Not Hispanic or Latino	19	7
Race/Ethnicity, Customized
Units: Subjects
Asian	1	0
White	19	7

End points

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Reporting group title

Ruxolitinib-naïve Subjects With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib-naïve Subjects Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib-Resistant or Intolerant With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Reporting group title

Ruxolitinib-Resistant or Intolerant Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)

Subject analysis set title

Ruxolitinib-Naïve Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Subject analysis set title

Ruxolitinib-Resistant or Intolerant Subjects

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Primary: Percentage of Ruxolitinib-Naïve Subjects With Splenomegaly at Baseline who Achieved Composite Response at Week 32

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End point title

Percentage of Ruxolitinib-Naïve Subjects With Splenomegaly at Baseline who Achieved Composite Response at Week 32 ^[1] ^[2]

End point description

Composite response is defined as hematocrit (Hct) control without phlebotomy and ≥35% decrease in spleen size by imaging at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct of ≥45% that was ≥3% higher than baseline level or a Hct of >48%. One Cycle is 28 Days.

End point type

Primary

End point timeframe

Week 32

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: Only descriptive statistics was planned to be reported in the endpoint.
[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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects With Splenomegaly
Number of subjects analysed	9
Units: Percentage of Subjects
number (not applicable)	44.4

No statistical analyses for this end point

Primary: Percentage of Ruxolitinib-Naïve Subjects Without Splenomegaly at Baseline who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32

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End point title

Percentage of Ruxolitinib-Naïve Subjects Without Splenomegaly at Baseline who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32 ^[3] ^[4]

End point description

Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

End point type

Primary

End point timeframe

Week 32

Notes
[3] - 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: Only descriptive statistics was planned to be reported in the endpoint.
[4] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects Without Splenomegaly
Number of subjects analysed	2
Units: Percentage of Subjects
number (not applicable)	100

No statistical analyses for this end point

Primary: Percentage of All Ruxolitinib-Naïve Subjects (Irrespective of Spleen Size) who Achieved Hct Control Without Phlebotomy at Week 32

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End point title

Percentage of All Ruxolitinib-Naïve Subjects (Irrespective of Spleen Size) who Achieved Hct Control Without Phlebotomy at Week 32 ^[5] ^[6]

End point description

End point type

Primary

End point timeframe

Week 32

Notes
[5] - 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: Only descriptive statistics was planned to be reported in the endpoint.
[6] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly
Number of subjects analysed	9	2
Units: Percentage of Subjects
number (not applicable)	44.4	100

No statistical analyses for this end point

Primary: Percentage of All Ruxolitinib-Resistant or Intolerant Subjects who Achieved Hct Control Without Phlebotomy at Week 32

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End point title

Percentage of All Ruxolitinib-Resistant or Intolerant Subjects who Achieved Hct Control Without Phlebotomy at Week 32 ^[7] ^[8]

End point description

End point type

Primary

End point timeframe

From Baseline to Week 32 (Cycle 8 Day 28)

Notes
[7] - 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: Only descriptive statistics was planned to be reported in the endpoint.
[8] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	4	1
Units: Percentage of Subjects
number (not applicable)	75.0	0

No statistical analyses for this end point

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Response at Week 32

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End point title

Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Response at Week 32

End point description

Complete hematologic response requires all of the following: Hct control without phlebotomy; White blood cell (WBC) count ≤10 × 10^9/Liter (L) at Week 32; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

End point type

Secondary

End point timeframe

Week 32 (Cycle 8 Day 28)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	9	2	4	1
Units: Percentage of Subjects
number (not applicable)	33.3	100	75.0	0

No statistical analyses for this end point

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Remission at Cycle 11 Day 28

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End point title

Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Remission at Cycle 11 Day 28

End point description

Complete hematologic remission requires all of the following: Hct control without phlebotomy between Weeks 32 and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

End point type

Secondary

End point timeframe

Cycle 11 Day 28

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Subjects
number (not applicable)	40	100	0	0

No statistical analyses for this end point

Secondary: Duration of Complete Hematologic Remission, with a Durable Responder Defined as a Subject in Remission at Week 32 and Cycle 11 Day 28

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End point title

Duration of Complete Hematologic Remission, with a Durable Responder Defined as a Subject in Remission at Week 32 and Cycle 11 Day 28

End point description

Complete hematologic remission requires all of the following: Hct control without phlebotomy between Week 32 (Cycle 8 Day 28) and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%

End point type

Secondary

End point timeframe

Week 32 (Cycle 8 Day 28), Cycle 11 Day 28

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[9]	5 ^[10]	6 ^[11]	1 ^[12]
Units: Subjects
number (not applicable)
Cycle 11, Day 28	2	1	0	0
Week 32	3	2	3	0

Notes
[9] - Subject number analyzed Cycle 11, Day 28 - 5 Week 32 - 9
[10] - Subject number analyzed Cycle 11, Day 28 - 1 Week 32 - 2
[11] - Subject number analyzed Cycle 11, Day 28 - 1 Week 32 - 4
[12] - Subject number analyzed Cycle 11, Day 28 - 1 Week 32 - 1

No statistical analyses for this end point

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline by Response per Modified European Leukemia Net (ELN) Criteria

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End point title

Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline by Response per Modified European Leukemia Net (ELN) Criteria ^[13]

End point description

Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

Notes
[13] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly
Number of subjects analysed	15 ^[14]	6 ^[15]
Units: Percentage of Subjects
number (not applicable)
Baseline	0	0
Cycle 3, Day 28	73.3	83.3
Cycle 5, Day 28	76.9	80.0
Cycle 8, Day 28 (Week 32)	66.7	75.0
Cycle 11, Day 28	80	100
Cycle 12, Day 28	80	100
Cycle 14, Day 28	80	100
Cycle 17, Day 28	33.3	0
Cycle 20, Day 28	100	0
Final Visit (28 Days post-last dose)	20	33.3

Notes
[14] - Only subjects for whom data were collected are included in the analysis.
[15] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline by Response per Modified ELN Criteria

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End point title

Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline by Response per Modified ELN Criteria ^[16]

End point description

Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter until end of study (up to 2 years)

Notes
[16] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	5 ^[17]	1 ^[18]
Units: Percentage of Subjects
number (not applicable)
Baseline	0	0
Cycle 3, Day 28	100	0
Cycle 5 Day 28	100	0
Cycle 8, Day 28 (Week 32)	100	0
Cycle 14, Day 28	100	0
Cycle 17, Day 28	100	0
Cycle 20, Day 28	0	0
Final (28 Days post-last dose)	75.0	0
Cycle 11, Day 28	100	0

Notes
[17] - Only subjects for whom data were collected are included in the analysis.
[18] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) by Response per Modified ELN Criteria

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End point title

Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) by Response per Modified ELN Criteria

End point description

Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[19]	7 ^[20]
Units: Percentage of Subjects
number (not applicable)
Baseline	0	0
Cycle 3, Day 28	78.9	71.4
Cycle 5 Day 28	81.3	66.7
Cycle 8, Day 28 (Week 32)	72.7	60
Cycle 11, day 28	83.3	50
Cycle 14, Day 28	83.3	50
Cycle 17, Day 28	50	0
Cycle 20, Day 28	100	0
Final (28 Days post-last dose)	35.7	25

Notes
[19] - Only subjects for whom data were collected are included in the analysis.
[20] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

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End point title

Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32 ^[21]

End point description

The percentage of Subjects with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the Subjects qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

Notes
[21] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly
Number of subjects analysed	15 ^[22]	6 ^[23]
Units: Percentage of Participants
number (not applicable)
HCT Control	42.9	100
Composite Response	0	0
ELN Response	50	75
Complete Hematologic Response	28.6	66.7

Notes
[22] - Only subjects for whom data were collected are included in the analysis.
[23] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

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End point title

Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32 ^[24]

End point description

The duration of response in Subjects with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the Subjects qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

Notes
[24] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly
Number of subjects analysed	15 ^[25]	6 ^[26]
Units: Subjects
number (not applicable)
HCT Control	3	3
Composite Response	0	0
ELN Response	4	3
Complete Hematologic Response	2	2

Notes
[25] - Only subjects for whom data were collected are included in the analysis.
[26] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

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End point title

Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32 ^[27]

End point description

End point type

Secondary

End point timeframe

From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

Notes
[27] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	5 ^[28]	1 ^[29]
Units: Percentage of Subjects
number (not applicable)
HCT Control	100	0
Composite Response	0	0
ELN Response	100	0
Complete Hematologic Response	100	0

Notes
[28] - Only subjects for whom data were collected are included in the analysis.
[29] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

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End point title

Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32 ^[30]

End point description

End point type

Secondary

End point timeframe

From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

Notes
[30] - 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: Data for this endpoint was provided only for those arms which were planned to be reported.

End point values	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	5 ^[31]	1 ^[32]
Units: Subjects
number (not applicable)
HCT Control	2	0
Composite Response	0	0
ELN Response	2	0
Complete Hematologic Response	2	0

Notes
[31] - Only subjects for whom data were collected are included in the analysis.
[32] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks from Week 32

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End point title

Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks from Week 32

End point description

End point type

Secondary

End point timeframe

Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[33]	7 ^[34]
Units: Percentage of Subjects
number (not applicable)
HCT Control	55.6	75
Composite Response	0	0
ELN Response	60	60
Complete Hematologic Response	44.4	50

Notes
[33] - Only subjects for whom data were collected are included in the analysis.
[34] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Duration of Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) with Durable Response Lasting at Least 12 Weeks From Week 32

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End point title

Duration of Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) with Durable Response Lasting at Least 12 Weeks From Week 32

End point description

The duration of response in Subjects with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the Subjects qualify. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[35]	7 ^[36]
Units: Subjects
number (not applicable)
HCT Control	5	3
Composite Response	0	0
ELN Response	6	3
Complete Hematologic Response	4	2

Notes
[35] - Only subjects for whom data were collected are included in the analysis.
[36] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Total Number of Subjects With Adverse Events by Severity, Graded According to NCI CTCAE v4.0

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End point title

Total Number of Subjects With Adverse Events by Severity, Graded According to NCI CTCAE v4.0

End point description

An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) will be used for assessing adverse event severity. During the final analyses, the focus was on the Adverse Events of severity grades >/=3 as shown below. The extensive listings of all grade AEs are available at request. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Subjects
number (not applicable)
Baseline	0	0	0	0
Grade 3-5 AE	5	2	3	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Hematology Parameters.

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End point title

Percentage of Subjects With Clinical Laboratory Abnormalities: Hematology Parameters.

End point description

Hematology parameter laboratory values falling outside the standard reference range will be recorded as either high or low. There was no clinical laboratory abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Subjects
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters

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End point title

Percentage of Subjects With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters

End point description

Clinical chemistry parameter laboratory values falling outside the standard reference range will be recorded as either high or low. There was no clinical chemistry abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Subjects
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Urinalysis Parameters

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End point title

Percentage of Subjects With Clinical Laboratory Abnormalities: Urinalysis Parameters

End point description

Urinalysis parameter laboratory values falling outside the standard reference range will be recorded as either high or low. There was no clinical laboratory (urinalysis) abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Subjects
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations

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End point title

Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations

End point description

Vital signs were measured prior to the infusion while the subject was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[37]	5 ^[38]	6 ^[39]	1 ^[40]
Units: Millisecond (msec)
arithmetic mean (standard deviation)
PR Duration Baseline	158.93 ± 24.86	153.60 ± 22.55	152.00 ± 17.39	196.00 ± 0
PQ(PR) Durations Cycle 1, Day 1, 4 hour	0.60 ± 10.89	-2.60 ± 5.37	-2.00 ± 9.72	4.00 ± 0
PQ(PR) Durations Cycle 1, Day 1, 6 hour	-2.80 ± 8.10	-4.40 ± 15.52	6.00 ± 25.49	0.00 ± 0
PQ(PR) Durations Cycle 1, Day 2, pre-dose	-14.00 ± 0	-6.00 ± 0	0 ± 0	0 ± 0
PQ(PR) Durations Cycle 1, Day 2, 24 hour	1.93 ± 10.32	1.00 ± 16.45	0.67 ± 22.01	-12.00 ± 0
PQ(PR) Durations Cycle ,1 Day 5, pre-dose	-1.00 ± 11.70	-12.00 ± 9.38	0.40 ± 26.59	-4.00 ± 0
PQ(PR) Durations Cycle 1, Day 5, 4 hour	-8.00 ± 12.68	-6.25 ± 15.59	-1.20 ± 29.52	0 ± 0
PQ(PR) Durations Cycle 1, Day 5, 6 hour	-4.77 ± 14.08	-2.75 ± 10.81	7.60 ± 27.29	0 ± 0
PQ(PR) Durations Cycle 2, Day1, pre-dose	1.43 ± 14.26	-5.75 ± 11.79	-2.33 ± 11.89	-8.00 ± 0
PQ(PR) Durations Cycle 3, Day 1, pre-dose	-6.00 ± 0	0 ± 0	0 ± 0	0 ± 0
PQ(PR) Durations Cycle 3, Day 1, 4 hour	-8.00 ± 0	0 ± 0	0 ± 0	0 ± 0
PQ(PR) Durations Cycle 3, Day 1, 6 hour	-6.00 ± 0	0 ± 0	0 ± 0	0 ± 0
PQ(PR) Durations Cycle 4, Day 1, pre-dose	-20.00 ± 0	0 ± 0	0 ± 0	0 ± 0
PQ(PR) Durations Cycle 4, Day 1, 4 hour	-20.00 ± 0	0 ± 0	0.00 ± 0	0 ± 0
QRS Duration Baseline	90.87 ± 8.25	83.80 ± 6.42	83.33 ± 9.77	94.00 ± 0
QRS Cycle 1 Day 1 (4 H)	-1.47 ± 5.83	4.60 ± 6.69	1.33 ± 1.03	0 ± 0
QRS Cycle 1 Day 1 (6 H)	-1.27 ± 5.27	4.00 ± 3.08	0.33 ± 5.28	-2.00 ± 0
QRS Cycle 1 Day 2 (PREDOSE)	-4.00 ± 0	2.00 ± 0	0.00 ± 2.00	2.00 ± 0
QRS Cycle 1 Day 2 (24 H)	1.07 ± 3.77	1.75 ± 6.55	3.00 ± 11.64	-2.00 ± 0
QRS Cycle 1 Day 5 (PREDOSE)	0.13 ± 4.63	4.00 ± 9.09	0.00 ± 2.00	2.00 ± 0
QRS Cycle 1 Day 5 (4 H)	-1.08 ± 3.12	3.75 ± 9.46	-0.40 ± 2.61	0 ± 0
QRS Cycle 1 Day 5 (6 H)	-0.92 ± 4.73	-0.25 ± 5.19	2.00 ± 5.83	0 ± 0
QRS Cycle 2 Day 1 (PREDOSE)	0.64 ± 6.25	7.75 ± 9.46	1.00 ± 2.76	-4.00 ± 0
QRS Cycle 3 Day 1 (PREDOSE)	-4.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QRS Cycle 3 Day 1 (4 H)	-4.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QRS Cycle 3 Day 1 (6 H)	-4.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QRS Cycle 4 Day 1 (PREDOSE)	-2.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QRS Cycle 4 Day 1 (4 H)	-2.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QT Duration Baseline	396.67 ± 31.96	392.60 ± 38.74	386.00 ± 16.78	392.00 ± 0
QT Duration Cycle 1 Day 1 (4 H)	-7.33 ± 26.43	16.80 ± 13.44	5.67 ± 10.07	36.00 ± 0
QT Duration Cycle 1 Day 1 (6 H)	-9.40 ± 23.70	11.00 ± 29.14	-1.33 ± 13.49	36.00 ± 0
QT Duration Cycle 1 Day 2 (PREDOSE)	-6.00 ± 0	-18.00 ± 0	0 ± 0	0 ± 0
QT Duration Cycle 1 Day 2 (24 H)	-10.21 ± 25.57	2.75 ± 29.00	7.00 ± 16.58	0 ± 0
QT Duration Cycle 1 Day 5 (PREDOSE)	-6.20 ± 19.79	-8.75 ± 21.00	8.00 ± 19.54	4.00 ± 0
QT Duration Cycle 1 Day 5 (4 H)	-4.31 ± 33.31	15.25 ± 15.65	3.20 ± 24.23	-12.00 ± 0
QT Duration Cycle 1 Day 5 (6 H)	-10.31 ± 24.83	4.75 ± 20.93	7.60 ± 16.40	-4.00 ± 0
QT Duration Cycle 2 Day 1 (PREDOSE)	5.00 ± 22.68	10.50 ± 25.96	19.00 ± 13.67	12.00 ± 0
QT Durations Cycle 3 Day 1 (PREDOSE)	-2.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QT Durations Cycle 3 Day 1 (4 H)	-10.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QT Durations Cycle 3 Day 1 (6 H)	-4.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QT Durations Cycle 4 Day 1 (PREDOSE)	-16.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QT Durations Cycle 4 Day 1 (4 H)	-16.00 ± 0	-4.75 ± 6.18	-1.60 ± 15.44	-12.00 ± 0
QTcB baseline	427.67 ± 24.23	419.60 ± 7.70	424.50 ± 25.74	444.00 ± 0
QTcB - Cycle 1 Day 1 (4 H)	3.80 ± 12.82	21.00 ± 11.14	13.83 ± 14.05	-30.00 ± 0
QTcB - Cycle 1 Day 1 (6 H)	8.00 ± 10.54	8.40 ± 22.40	6.33 ± 5.50	5.00 ± 0
QTcB - Cycle 1 Day 2 (PREDOSE)	-15.00 ± 0	-410.00 ± 0	0 ± 0	0 ± 0
QTcB - Cycle 1 Day 2 (24 H)	3.71 ± 15.59	-0.75 ± 16.40	4.50 ± 14.47	-14.00 ± 0
QTcB - Cycle 1 Day 5 (PREDOSE)	-11.07 ± 15.21	-10.00 ± 8.76	-9.20 ± 15.25	-7.00 ± 0
QTcB - Cycle 4 Day 1 (4 H)	-62.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcB - Cycle 1 Day 5 (4 H)	-2.92 ± 14.20	1.50 ± 8.81	-4.60 ± 18.70	0.00 ± 0
QTcB - Cycle 1 Day 5 (6 H)	-4.54 ± 16.10	-4.75 ± 6.18	-1.60 ± 15.44	-12.00 ± 0
QTcB - Cycle 2 Day 1 (PREDOSE)	3.93 ± 14.42	7.75 ± 20.61	0.17 ± 14.54	-23.00 ± 0
QTcB - Cycle 3 Day 1 (PREDOSE)	-16.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcB - Cycle 3 Day 1 (4 H)	6.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcB - Cycle 3 Day 1 (6 H)	8.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcB - Cycle 4 Day 1 (PREDOSE)	-62.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Baseline	417.93 ± 22.41	410.00 ± 17.62	411.17 ± 17.90	426.00 ± 0
QTcF Cycle 1 Day 2 (PREDOSE)	-12.00 ± 0	-20.00 ± 0	0 ± 0	0 ± 0
QTcF Cycle 1 Day 2 (24 H)	-2.36 ± 13.32	0.00 ± 20.46	5.33 ± 14.81	-9.00 ± 0
QTcF Cycle 1 Day 5 (PREDOSE)	-10.47 ± 14.17	-9.25 ± 8.96	-3.20 ± 14.60	-3.00 ± 0
QTcF Cycle 1 Day 5 (4 H)	-0.08 ± 26.39	4.00 ± 8.98	-2.00 ± 17.36	-4.00 ± 0
QTcF Cycle 1 Day 5 (6 H)	-7.85 ± 13.44	-2.25 ± 8.46	1.60 ± 14.10	6.00 ± 0
QTcF Cycle 2 Day 1 (PREDOSE)	3.36 ± 10.49	8.0 ± 20.51	6.83 ± 12.45	-11.00 ± 0
QTcF Cycle 3 Day 1 (PREDOSE)	-11.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Cycle 3 Day 1 (4 H)	0.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Cycle 3 Day 1 (6 H)	4.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Cycle 4 Day 1 (PREDOSE)	-45.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Cycle 4 Day 1 (4 H)	-45.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcF Cycle 1 Day 1 (4 H)	-1.27 ± 11.86	18.80 ± 10.08	11.67 ± 11.09	-8.0 ± 0
QTcF Cycle 1 Day 1 (6 H)	1.00 ± 8.78	10.00 ± 21.64	3.5 ± 7.37	16.00 ± 0
RR Duration Baseline	861.47 ± 133.95	881.00 ± 151.46	835.83 ± 139.93	779.00 ± 0
RR Duration Cycle 1 Day 2 (PREDOSE)	28.00 ± 0	18.00 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 1 Day 2 (24 H)	-51.50 ± 121.75	17.25 ± 65.17	8.83 ± 29.78	54.00 ± 0
RR Duration Cycle 1 Day 5 (PREDOSE)	25.87 ± 97.32	-0.75 ± 104.53	67.80 ± 78.89	43.00 ± 0
RR Duration Cycle 1 Day 5 (4 H)	-26.23 ± 114.00	79.75 ± 62.99	24.20 ± 114.05	-47.00 ± 0
RR Duration Cycle 1 Day 5 (6 H)	-21.46 ± 121.82	49.50 ± 99.21	33.00 ± 59.05	-56.00 ± 0
RR Duration Cycle 2 Day 1 (PREDOSE)	7.14 ± 118.26	23.75 ± 86.53	78.17 ± 59.85	144.00 ± 0
RR Duration Cycle 3 Day 1 (PREDOSE)	48.00 ± 0	0 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 3 Day 1 (4 H)	-59.00 ± 0	0 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 3 Day 1 (6 H)	-43.00 ± 0	0 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 4 Day 1 (PREDOSE)	182.00 ± 0	0 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 4 Day 1 (4 H)	182.00 ± 0	0 ± 0	0 ± 0	0 ± 0
QTcB Cycle 4 Day 1 (4 H)	-62.00 ± 0	0 ± 0	0 ± 0	0 ± 0
RR Duration Cycle 1 Day 1 4 H	-38.87 ± 130.21	-5.60 ± 58.23	-36.50 ± 66.76	292.00 ± 0
RR Duration Cycle 1 Day 1 6 H	-65.67 ± 117.44	14.00 ± 100.82	-31.17 ± 49.04	130.00 ± 0

Notes
[37] - Only subjects for whom data were collected are included in the analysis.
[38] - Only subjects for whom data were collected are included in the analysis.
[39] - Only subjects for whom data were collected are included in the analysis.
[40] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Heart Rate, as Measured by Electrocardiogram

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End point title

Change from Baseline in Heart Rate, as Measured by Electrocardiogram

End point description

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[41]	5 ^[42]	6 ^[43]	1 ^[44]
Units: Beats per Minute
arithmetic mean (standard deviation)
Baseline	71.47 ± 12.74	69.80 ± 12.28	73.17 ± 10.07	77.00 ± 0
Cycle 1, Day 1, 4 Hour	4.40 ± 10.58	0.60 ± 5.32	2.50 ± 4.23	-21.00 ± 0
Cycle 1, Day 1, 6 Hour	6.20 ± 10.35	-0.60 ± 8.65	3.00 ± 5.44	-11.00 ± 0
Cycle 1 Day 2, pre-dose	-3.00 ± 0	-1.00 ± 0	0 ± 0	0 ± 0
Cycle 1 Day 2, 24 Hour	4.71 ± 10.31	-1.75 ± 5.32	-0.67 ± 2.50	72.43 ± 9.59
Cycle 1 Day 5, pre-dose	-1.47 ± 6.56	-0.75 ± 8.14	-5.60 ± 5.27	-4.00 ± 0
Cycle 1 Day 5, 4 hour	2.69 ± 8.61	-5.00 ± 2.94	-2.20 ± 7.92	5.00 ± 0
Cycle 1 Day 5, 6 hour	2.23 ± 9.39	-3.75 ± 7.76	-2.80 ± 4.92	6.00 ± 0
Cycle 2, Day 1, pre-dose	-1.43 ± 9.83	-1.50 ± 8.39	-6.17 ± 5.19	-12.00 ± 0
Cycle 3 Day 1, pre-dose	-5.00 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 3 Day 1, 4 hour	7.00 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 3 Day 1, 6 hour	5.00 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 4 Day 1, pre-dose	-16.00 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 4 Day 1, 4 hour	-16.00 ± 0	0 ± 0	0 ± 0	0 ± 0

Notes
[41] - Only subjects for whom data were collected are included in the analysis.
[42] - Only subjects for whom data were collected are included in the analysis.
[43] - Only subjects for whom data were collected are included in the analysis.
[44] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Oral Temperature

Top of page

End point title

Change from Baseline in Oral Temperature

End point description

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[45]	5 ^[46]	6 ^[47]	1 ^[48]
Units: Degrees Celsius (C)
arithmetic mean (standard deviation)
Baseline	36.50 ± 0.37	36.40 ± 0.25	36.47 ± 0.28	37.10 ± 0
Cycle 1 Day 15	0.13 ± 0.33	0.42 ± 0.50	0.18 ± 0.32	-0.30 ± 0
Cycle 1 Day 22	0.03 ± 0.18	0.04 ± 0.29	0.15 ± 0.21	-0.50 ± 0
Cycle 2 Day 1	-0.05 ± 0.28	0.05 ± 0.30	0.17 ± 0.34	-0.60 ± 0
Cycle 2 Day 15	0.04 ± 0.27	0.18 ± 0.24	0.23 ± 0.38	-0.30 ± 0
Cycle 3 Day 1	-0.09 ± 0.36	0.13 ± 0.45	0.17 ± 0.43	0.10 ± 0
Cycle 3 Day 15	-0.04 ± 0.31	-0.03 ± 0.06	0.10 ± 0.26	-0.20 ± 0
Cycle 4 Day 1	-0.05 ± 0.26	-0.17 ± 0.15	0.06 ± 0.37	-0.50 ± 0
Cycle 5 Day 1	0.05 ± 0.16	-0.10 ± 0.36	0.10 ± 0.32	-0.80 ± 0
Cycle 6 Day 1	-0.03 ± 0.16	-0.10 ± 0.45	0.12 ± 0.16	-0.40 ± 0
Cycle 7 Day 1	0.01 ± 0.30	-0.20 ± 0.28	0.20 ± 0.26	-0.60 ± 0
Cycle 8 Day 1	-0.01 ± 0.20	-0.05 ± 0.64	0.20 ± 0.36	-0.30 ± 0
Cycle 9 Day 1	0.03 ± 0.13	0.05 ± 0.35	-0.07 ± 0.42	-0.40 ± 0
Cycle 10 Day 1	-0.08 ± 0.10	0.30 ± 0.42	0.10 ± 0.35	-0.60 ± 0
Cycle 11 Day 1	-0.07 ± 0.19	-0.20 ± 0	-0.10 ± 0.14	-0.40 ± 0
Cycle 12 Day 1	-0.10 ± 0.16	0.30 ± 0	-0.20 ± 0.14	-0.70 ± 0
Cycle 13 Day 1	0.00 ± 0.19	-0.70 ± 0	0 ± 0	-0.70 ± 0
Cycle 14 Day 1	0.00 ± 0.41	-0.10 ± 0	-0.30 ± 0	-0.70 ± 0
Cycle 15 Day 1	-0.10 ± 0.14	-0.30 ± 0	-0.40 ± 0	-0.50 ± 0
Cycle 16 Day 1	0.03 ± 0.30	-0.80 ± 0	-0.10 ± 0	-0.50 ± 0
Cycle 17 Day 1	0.03 ± 0.12	0.60 ± 0	0.00 ± 60	-0.80 ± 0
Cycle 18 Day 1	0.07 ± 0.15	0 ± 0	-0.20 ± 0	-0.80 ± 0
Cycle 19 Day 1	-0.15 ± 0.21	0 ± 0	0 ± 0	0 ± 0
Cycle 20 Day 1	0.00 ± 0.14	0 ± 0	0 ± 0	-0.50 ± 0
Cycle 21 Day 1	0 ± 0	0 ± 0	0 ± 0	-0.40 ± 0
Cycle 22 Day 1	-0.50 ± 0	0 ± 0	0 ± 0	-0.70 ± 0
Cycle 23 Day 1	0 ± 0	0 ± 0	0 ± 0	-0.80 ± 0
Final Visit	-0.08 ± 0.15	0.26 ± 0.26	0.08 ± 0.37	-0.50 ± 0

Notes
[45] - Only subjects for whom data were collected are included in the analysis.
[46] - Only subjects for whom data were collected are included in the analysis.
[47] - Only subjects for whom data were collected are included in the analysis.
[48] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Pulse Rate

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End point title

Change from Baseline in Pulse Rate

End point description

Vital signs were measured prior to the infusion while the subject was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance. The study was pre-maturely terminated, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[49]	5 ^[50]	6 ^[51]	1 ^[52]
Units: Beats per Minute
arithmetic mean (standard deviation)
Baseline	74.7 ± 12.3	71.6 ± 9.2	76.7 ± 14.1	68.0 ± 0
Cycle 1 Day 15	4.5 ± 13.2	5.4 ± 5.5	-0.7 ± 4.8	7.0 ± 0
Cycle 1 Day 22	3.9 ± 11.3	8.2 ± 4.9	-5.8 ± 3.9	8.0 ± 0
Cycle 2 Day 1	-1.1 ± 8.6	1.8 ± 8.7	-9.3 ± 6.1	12.0 ± 0
Cycle 2 Day 15	0.1 ± 11.0	1.8 ± 8.5	-5.8 ± 5.5	9.0 ± 0
Cycle 3 Day 1	-2.8 ± 9.4	-2.0 ± 8.6	-4.2 ± 9.9	9.0 ± 0
Cycle 3 Day 15	-1.2 ± 9.7	10.8 ± 13.6	-2.2 ± 11.0	21.0 ± 0
Cycle 4 Day 1	1.0 ± 11.2	1.7 ± 9.9	-6.6 ± 9.8	24.0 ± 0
Cycle 5 Day 1	0.6 ± 8.4	-4.0 ± 9.3	-3.6 ± 4.2	28.0 ± 0
Cycle 6 Day 1	0.4 ± 9.1	-4.3 ± 6.8	-1.6 ± 6.8	14.0 ± 0
Cycle 7 Day 1	1.4 ± 14.6	1.5 ± 16.3	-1.0 ± 9.8	21.0 ± 0
Cycle 8 Day 1	-3.9 ± 13.3	-1.0 ± 12.7	0.5 ± 3.1	11.0 ± 0
Cycle 9 Day 1	-5.4 ± 6.4	0.0 ± 5.7	0.3 ± 2.5	0 ± 0
Cycle 10 Day 1	-0.3 ± 9.9	8.5 ± 19.1	2.3 ± 8.5	20.0 ± 0
Cycle 11 Day 1	-2.5 ± 11.5	-2.0 ± 0	2.5 ± 0.7	37.0 ± 0
Cycle 12, Day 1	-0.2 ± 11.6	-6.0 ± 0	-1.0 ± 4.2	21.0 ± 0
Cycle 13, Day 1	-2.8 ± 7.8	-5.0 ± 0	-1.0 ± 0	16.0 ± 0
Cycle 14, Day 1	-3.8 ± 11.1	-2.0 ± 0	-4.0 ± 0	12.0 ± 0
Cycle 15 Day 1	-0.8 ± 10.4	10.0 ± 0	-2.0 ± 0	14.0 ± 0
Cycle 16 Day 1	-1.3 ± 15.6	-2.0 ± 0	-2.0 ± 0	16.0 ± 0
Cycle 17, Day 1	-12.7 ± 9.5	9.0 ± 0	1.0 ± 0	22.0 ± 0
Cycle 18, Day 1	-4.3 ± 3.5	0 ± 0	-3.0 ± 0	16.0 ± 0
Cycle 19, Day 1	-9.0 ± 5.7	0 ± 0	6.0 ± 0	15.0 ± 0
Cycle 20, Day 1	-5.0 ± 9.9	0 ± 0	4.0 ± 0	5.0 ± 0
Cycle 21, Day 1	2.0 ± 0	0 ± 0	0 ± 0	17.0 ± 0
Cycle 22, Day 1	-8.0 ± 0	0 ± 0	0 ± 0	14 ± 0
Cycle 23, Day 1	0 ± 0	0 ± 0	0 ± 0	19.0 ± 0
Final Visit	-1.7 ± 12.2	0.2 ± 11.6	0.2 ± 10.1	16.0 ± 0

Notes
[49] - Only subjects for whom data were collected are included in the analysis.
[50] - Only subjects for whom data were collected are included in the analysis.
[51] - Only subjects for whom data were collected are included in the analysis.
[52] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Respiratory Rate

Top of page

End point title

Change from Baseline in Respiratory Rate

End point description

Vital signs were measured prior to the infusion while the subject was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance. The study was pre-maturely terminated, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[53]	5 ^[54]	6 ^[55]	1 ^[56]
Units: Breaths per Minute
arithmetic mean (standard deviation)
Baseline	17.4 ± 2.0	17.4 ± 1.9	18.2 ± 2.6	16.0 ± 0
Cycle 1 Day 15	-0.3 ± 1.0	-0.2 ± 1.8	-0.2 ± 1.8	0 ± 0
Cycle 1 Day 22	-0.5 ± 0.8	0.2 ± 0.4	-0.5 ± 2.2	0 ± 0
Cycle 2 Day 1	-0.3 ± 1.5	-0.3 ± 1.7	-0.4 ± 1.7	0 ± 0
Cycle 2 Day 15	-0.2 ± 1.0	0.0 ± 0.8	-1.2 ± 1.8	2.0 ± 0
Cycle 3 Day 1	-0.7 ± 1.3	-1.5 ± 3.1	-1.8 ± 1.8	0 ± 0
Cycle 3 Day 15	-0.7 ± 1.3	0.0 ± 1.0	-1.0 ± 1.0	0 ± 0
Cycle 4 Day 1	-0.3 ± 1.3	-3.3 ± 4.2	-1.0 ± 1.0	2.0 ± 0
Cycle 5 Day 1	-0.4 ± 1.9	-0.3 ± 0.6	1.0 ± 2.2	0 ± 0
Cycle 6 Day 1	-0.5 ± 1.3	-0.5 ± 1.9	-0.6 ± 1.3	2.0 ± 0
Cycle 7 Day 1	-0.2 ± 1.7	0 ± 0	-2.3 ± 1.5	2.0 ± 0
Cycle 8 Day 1	0.1 ± 1.5	-0.5 ± 2.1	-0.8 ± 3.8	0 ± 0
Cycle 9 Day 1	0.4 ± 1.8	0.5 ± 0.7	-1.7 ± 6.0	-2.0 ± 0
Cycle 10 Day 1	-0.2 ± 1.6	-0.5 ± 2.1	-0.3 ± 5.5	0 ± 0
Cycle 11 Day 1	-0.8 ± 1.0	1.0 ± 0	-0.5 ± 0.7	2.0 ± 0
Cycle 12 Day 1	-0.4 ± 1.5	1.0 ± 0	1.5 ± 0.7	0 ± 0
Cycle 13 Day 1	-1.4 ± 2.8	1.0 ± 0	-1.0 ± 0	2.0 ± 0
Cycle 14 Day 1	0.8 ± 2.3	1.0 ± 0	1.0 ± 0	0 ± 0
Cycle 15 Day 1	0.0 ± 1.4	1.0 ± 0	-1.0 ± 0	0 ± 0
Cycle 16 Day 1	-0.3 ± 1.3	1.0 ± 0	-2.0 ± 0	0 ± 0
Cycle 17 Day 1	1.3 ± 2.3	1 ± 0	-2.0 ± 0	0 ± 0
Cycle 18 Day 1	1.3 ± 2.3	0 ± 0	-1.0 ± 0	2.0 ± 0
Cycle 19 Day 1	1.5 ± 2.1	0 ± 0	0 ± 0	2.0 ± 0
Cycle 20 Day 1	2.0 ± 2.8	0 ± 0	-3.0 ± 0	2.0 ± 0
Cycle 21 Day 1	2.0 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 22 Day 1	0.0 ± 0	0 ± 0	0 ± 0	0 ± 0
Cycle 23 Day 1	0 ± 0	0 ± 0	0 ± 0	0 ± 0
Final visit	-0.3 ± 1.5	-1.2 ± 1.5	-1.8 ± 1.8	0 ± 0

Notes
[53] - Only subjects for whom data were collected are included in the analysis.
[54] - Only subjects for whom data were collected are included in the analysis.
[55] - Only subjects for whom data were collected are included in the analysis.
[56] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Systolic Blood Pressure

Top of page

End point title

Change from Baseline in Systolic Blood Pressure

End point description

Vital signs were measured prior to the infusion while the subject was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance. The study was pre-maturely terminated, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[57]	5 ^[58]	6 ^[59]	1 ^[60]
Units: Millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
Cycle 1, Day 15	4.4 ± 9.9	3.6 ± 13.6	3.8 ± 15.1	5.0 ± 0
Cycle 1, Days 22	3.3 ± 9.4	-5.6 ± 11.8	4.8 ± 10.1	-5.0 ± 0
Cycle 2, Day 1	3.0 ± 10.3	2.8 ± 8.4	-4.3 ± 7.9	10.0 ± 0
Cycle 2 , Day 15	5.2 ± 9.8	-2.0 ± 13.6	-7.2 ± 9.6	30.0 ± 0
Cycle 3, Day 1	5.5 ± 10.8	-3.0 ± 9.8	7.3 ± 18.3	0 ± 0
Cycle 3, Day 15	1.2 ± 11.2	-3.5 ± 14.2	-3.8 ± 16.7	6.0 ± 0
Cycle 4, Day 1	2.2 ± 9.1	-7.3 ± 9.3	9.8 ± 8.1	13.0 ± 0
Cycle 5, Day 1	4.2 ± 10.5	-2.5 ± 6.8	3.3 ± 6.9	16.0 ± 0
Cycle 6 Day 1	11.2 ± 13.0	2.5 ± 9.7	8.6 ± 10.8	8.0 ± 0
Cycle 7 Day 1	4.7 ± 4.2	-4.0 ± 15.6	10.0 ± 5.0	29.0 ± 0
Cycle 8 Day 1	8.8 ± 9.0	5.0 ± 7.1	14.0 ± 18.8	9.0 ± 0
Cycle 9 Day 1	12.6 ± 8.3	3.0 ± 9.9	-4.3 ± 4.9	26.0 ± 0
Cycle 10 Day 1	11.8 ± 9.9	-3.0 ± 2.8	11.0 ± 13.2	30.0 ± 0
Cycle 11 Day 1	8.5 ± 12.3	14.0 ± 0	11.0 ± 12.7	34.0 ± 0
Cycle 12 Day 1	10.8 ± 11.5	-8.0 ± 0	6.5 ± 3.5	6.0 ± 0
Cycle 13 Day 1	13.4 ± 5.1	-8.0 ± 0	8.0 ± 0	14.0 ± 0
Cycle 14 Day 1	4.4 ± 14.7	18.0 ± 0	3.0 ± 0	14.0 ± 0
Cycle 15 Day 1	13.6 ± 7.5	14.0 ± 0	4.0 ± 0	5.0 ± 0
Cycle 16 Day 1	7.5 ± 8.6	8.0 ± 0	9.0 ± 0	4.0 ± 0
Cycle 17 Day 1	9.3 ± 5.8	24.0 ± 0	7.0 ± 0	6.0 ± 0
Cycle 18 Day 1	5.7 ± 4.2	0 ± 0	9.0 ± 0	13.0 ± 0
Cycle 19 Day 1	2.5 ± 3.5	0 ± 0	9.0 ± 0	13.0 ± 0
Cycle 20 Day 1	11.5 ± 9.2	0 ± 0	0 ± 0	13.0 ± 0
Cycle 21 Day 1	-18.0 ± 0	0 ± 0	0 ± 0	7.0 ± 0
Cycle 22 Day 1	24.0 ± 0	0 ± 0	0 ± 0	6.0 ± 0
Cycle 23 Day 1	0 ± 0	0 ± 0	0 ± 0	0 ± 0
Final visit	1.3 ± 9.7	7.6 ± 16.2	12.8 ± 23.9	19.0 ± 0
Baseline	129.3 ± 11.5	132.0 ± 17.2	122.3 ± 16.9	106.0 ± 0

Notes
[57] - Only subjects for whom data were collected are included in the analysis.
[58] - Only subjects for whom data were collected are included in the analysis.
[59] - Only subjects for whom data were collected are included in the analysis.
[60] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Change from Baseline in Diastolic Blood Pressure

Top of page

End point title

Change from Baseline in Diastolic Blood Pressure

End point description

Vital signs were measured prior to the infusion while the subject was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance. The last time point was Cycle 5 Day 1 due to early termination of the study.

End point type

Secondary

End point timeframe

Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15 ^[61]	5 ^[62]	6 ^[63]	1 ^[64]
Units: Millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
Baseline	76.3 ± 7.8	73.2 ± 5.2	72.3 ± 9.0	65.0 ± 0
Cycle1, Day 15	5.1 ± 8.7	10.0 ± 8.7	-1.8 ± 3.4	0.0 ± 0
Cycle 1, Day 22	3.6 ± 6.1	2.4 ± 3.2	-2.2 ± 5.8	-1.0 ± 0
Cycle 2, Day 1	6.1 ± 8.3	3.0 ± 2.9	-0.2 ± 9.3	3.0 ± 0
Cycle 2, Day 15	4.1 ± 6.3	2.5 ± 9.7	-5.5 ± 3.4	16.0 ± 0
Cycle 3 Day 1	6.2 ± 8.1	5.8 ± 10.0	-4.0 ± 12.4	5.0 ± 0
Cycle 3, Day 15	1.8 ± 10.5	2.0 ± 10.1	-7.5 ± 7.0	8.0 ± 0
Cycle 4, Day 1	5.5 ± 5.7	2.7 ± 6.8	-0.4 ± 5.0	1.0 ± 0
Cycle 5, Day 1	1.7 ± 6.1	5.0 ± 5.8	-5.0 ± 4.5	1.0 ± 0
Cycle 6, Day 1	5.9 ± 4.5	3.3 ± 11.1	-2.0 ± 9.5	12.0 ± 0
Cycle 7, Day 1	2.9 ± 4.8	4.5 ± 13.4	-5.3 ± 9.0	30.0 ± 0
Cycle 8, Day 1	7.8 ± 5.4	5.0 ± 7.1	0.5 ± 12.3	10.0 ± 0
Cycle 9, Day 1	4.1 ± 8.4	4.0 ± 5.7	-2.7 ± 1.5	4.0 ± 0
Cycle 10, Day 1	3.7 ± 5.9	5.0 ± 0	-2.3 ± 10.1	3.0 ± 0
Cycle 11, Day 1	9.7 ± 14.1	10.0 ± 0	1.0 ± 7.1	24.0 ± 0
Cycle 12, Day 1	9.8 ± 8.6	6.0 ± 0	2.0 ± 4.2	8.0 ± 0
Cycle 13, Day 1	9.0 ± 7.6	4.0 ± 0	2.0 ± 0	10.0 ± 0
Cycle 14, Day 1	5.6 ± 5.1	19.0 ± 0	-9.0 ± 0	11.0 ± 0
Cycle 15, Day 1	7.0 ± 8.0	10.0 ± 0	-2.0 ± 0	7.0 ± 0
Cycle 16, Day 1	9.8 ± 7.8	11.0 ± 0	7.0 ± 0	6.0 ± 0
Cycle 17, Day 1	11.3 ± 3.5	11.0 ± 0	3.0 ± 0	7.0 ± 0
Cycle 18, Day 1	5.0 ± 1.7	0 ± 0	-2.0 ± 0	3.0 ± 0
Cycle 19, Day 1	4.0 ± 5.7	0 ± 0	5.0 ± 0	8.0 ± 0
Cycle 20, Day 1	12.5 ± 3.5	0 ± 0	-1.0 ± 0	2.0 ± 0
Cycle 21, Day 1	-3.0 ± 0	0 ± 0	0 ± 0	7.0 ± 0
Cycle 22, Day 1	22.0 ± 0	0 ± 0	0 ± 0	8.0 ± 0
Cycle 23, Day 1	0 ± 0	0 ± 0	0 ± 0	7.0 ± 0
Final visit	5.8 ± 9.0	3.8 ± 14.0	-2.0 ± 12.6	11.0 ± 0

Notes
[61] - Only subjects for whom data were collected are included in the analysis.
[62] - Only subjects for whom data were collected are included in the analysis.
[63] - Only subjects for whom data were collected are included in the analysis.
[64] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time

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End point title

Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time

End point description

The ECOG performance status is a scale used to quantify cancer subjects' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction), 1=Symptomatic but completely ambulatory, 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Only baseline data were collectable. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

From Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Participant
number (not applicable)
0.0	66.7	60.0	50.0	100.0
1.0	33.3	40.0	50.0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Concomitant Medications

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End point title

Percentage of Subjects With Concomitant Medications

End point description

Subjects With Concomitant Medications at the baseline were reported and did not change during the study and the follow-up period. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

From Baseline to end of study (up to 2 years)

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Percentage of Subjects
number (not applicable)	100	100	100	100

No statistical analyses for this end point

Secondary: Maximum Serum Concentration Observed (Cmax) of Idasanutlin

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End point title

Maximum Serum Concentration Observed (Cmax) of Idasanutlin

End point description

Cmax is the maximum observed concentration of drug in blood. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Trough Concentration (Ctrough) of Idasanutlin

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End point title

Trough Concentration (Ctrough) of Idasanutlin

End point description

Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Time of Maximum Concentration Observed (tmax) of Idasanutlin

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End point title

Time of Maximum Concentration Observed (tmax) of Idasanutlin

End point description

Tmax is the time elapsed from the time of drug administration to maximum plasma concentration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Clearance (CL) of Idasanutlin

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End point title

Clearance (CL) of Idasanutlin

End point description

CL is a measure of the body's elimination of a drug from plasma over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Apparent Clearance (CL/F) of Idasanutlin

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End point title

Apparent Clearance (CL/F) of Idasanutlin

End point description

CL/F is a measure of the body's elimination of a drug from plasma over time, after oral administration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin

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End point title

Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin

End point description

Vdss/F is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the plasma. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Area Under the Concentration-Time Curve (AUC) of Idasanutlin

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End point title

Area Under the Concentration-Time Curve (AUC) of Idasanutlin

End point description

AUC (from zero to infinity) represents the total drug exposure over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-Naïve Subjects
Number of subjects analysed	20
Units: Number	0

No statistical analyses for this end point

Secondary: Half-life (t1/2) of Idasanutlin

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End point title

Half-life (t1/2) of Idasanutlin

End point description

t1/2 is defined as the time required for the drug plasma concentration to be reduced to half. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

End point type

Secondary

End point timeframe

Days 1, 2, and 5 of Cycles 1 and 4

End point values	Ruxolitinib-naïve Subjects With Splenomegaly	Ruxolitinib-naïve Subjects Without Splenomegaly	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly
Number of subjects analysed	15	5	6	1
Units: Number
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Baseline and Mean Change from Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time

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End point title

Baseline and Mean Change from Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time

End point description

The MPN-SAF TSS is an assessment form to measure the severity of 9 clinically important symptoms of polycythemia vera. These include: early satiety, abdominal discomfort, inactivity, concentration issues, night sweats, itching, bone pain, fever, and weight loss. The subject provides a severity score for each additional symptom on a scale of 0 (none/absent) to 10 (worst imaginable). A tenth symptom, fatigue, is assessed using the "worst" fatigue item from the Brief Fatigue Inventory (BFI). The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[65]	7 ^[66]
Units: Mean Change
arithmetic mean (standard deviation)
Baseline (Cycle 1 Day 1)	31.95 ± 19.95	26.00 ± 11.83
Cycle 2 Day 1	-5.06 ± 12.91	0.80 ± 26.37
Cycle 3 Day 28	-6.38 ± 12.71	-8.00 ± 15.08
Cycle 5 Day 28,	-7.00 ± 12.72	-9.50 ± 10.56
Week 32	-8.20 ± 12.79	-5.00 ± 15.26
Cycle 11 Day 28	-4.60 ± 3.71	-7.50 ± 3.54
Cycle 14 Day 28	-4.67 ± 5.54	-10.50 ± 4.95
Cycle 17 Day 28	-3.25 ± 5.38	-12.00 ± 1.41
Cycle 20 Day 28	-12.00 ± 0	-8.00 ± 0
Final Visit	-5.92 ± 9.96	-7.20 ± 5.63

Notes
[65] - Only subjects for whom data were collected are included in the analysis.
[66] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Baseline and Mean Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) Scores Over Time

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End point title

Baseline and Mean Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) Scores Over Time

End point description

EORTC QLQ-C30: includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores are averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study. Reported EORTC QLQ-C30 Scores include: Cognitive function, Diarrhea Emotional functioning, Nausea and vomiting, Social functioning, Physical functioning, Global health status/QoL, Role functioning.

End point type

Secondary

End point timeframe

Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[67]	7 ^[68]
Units: Mean Change
arithmetic mean (standard deviation)
Cognitive function Baseline	65.83 ± 32.21	76.19 ± 30.21
Cognitive function Cycle 2, Day 1	11.11 ± 11.43	8.33 ± 13.94
Cognitive function Cycle 3 Day 28	7.02 ± 16.02	6.67 ± 19.00
Cognitive function Cycle 5 Day 28	1.19 ± 22.13	11.11 ± 25.09
Cognitive function Week 32	6.06 ± 18.67	-3.33 ± 21.73
Cognitive function Cycle 11 Day 28	8.33 ± 13.94	0 ± 0
Cognitive function Cycle 14 Day 28	5.56 ± 17.21	0 ± 0
Cognitive function Cycle 17 Day 28	0.00 ± 13.61	-8.33 ± 11.79
Cognitive function Cycle 20 Day 28	0 ± 0	0 ± 0
Cognitive function Final Visit	4.44 ± 18.33	6.67 ± 9.13
Diarrhea Baseline	8.33 ± 18.34	14.29 ± 17.82
Diarrhea Cycle 2 Day 1	-5.56 ± 17.15	5.56 ± 13.61
Diarrhea Cycle 3 Day 28	1.75 ± 17.48	0 ± 0
Diarrhea Cycle 5 Day 28	7.14 ± 19.30	5.56 ± 13.61
Diarrhea Week 32	9.09 ± 26.21	20.0 ± 18.26
Diarrhea Cycle 11 Day 28	5.56 ± 13.61	0 ± 0
Diarrhea Cycle 14 Day 28	5.56 ± 13.61	0 ± 0
Diarrhea Cycle 17 Day 28	25.00 ± 31.91	0 ± 0
Diarrhea Cycle 20 Day 28	0 ± 0	0 ± 0
Diarrhea Final visit	13.33 ± 32.85	6.67 ± 14.91
Emotional functioning Baseline	65.83 ± 28.34	64.29 ± 21.36
Emotional functioning Cycle 1 Day 28	13.43 ± 20.24	15.28 ± 13.35
Emotional functioning Cycle 3 Day 28	14.04 ± 21.88	8.33 ± 10.21
Emotional functioning Cycle 5 Day 28	16.07 ± 20.53	6.94 ± 16.17
Emotional functioning Week 32	14.39 ± 18.29	5.00 ± 27.39
Emotional functioning Cycle 11 Day 28	6.94 ± 11.08	16.67 ± 0
Emotional functioning Cycle 14 Day 28	5.56 ± 10.09	-4.17 ± 5.89
Emotional functioning Cycle 17 Day 28	-8.33 ± 16.67	0 ± 0
Emotional functioning Cycle 20 Day 28	0 ± 0	8.33 ± 0
Emotional functioning Final visit	3.33 ± 18.31	16.67 ± 18.63
Nausea and vomiting Baseline	10.00 ± 16.58	2.38 ± 6.30
Nausea and vomiting Cycle 2 Day 1	-4.63 ± 12.53	8.33 ± 22.97
Nausea and vomiting Cycle 3 Day 28	-1.75 ± 17.48	3.33 ± 13.94
Nausea and vomiting Cycle 5 Day 28	-2.38 ± 11.05	8.33 ± 17.48
Nausea and vomiting Week 32	7.58 ± 23.99	16.67 ± 16.67
Nausea and vomiting Cycle 11 Day 28	2.78 ± 12.55	0 ± 23.57
Nausea and vomiting Cycle 14 Day 28	-2.78 ± 6.80	-8.33 ± 11.79
Nausea and vomiting Cycle 20 Day 28	0 ± 0	0 ± 0
Nausea and vomiting Final visit	11.11 ± 33.73	6.67 ± 19.00
Social functioning Baseline	67.50 ± 35.24	76.19 ± 13.11
Social functioning Cycle 2 Day 1	4.63 ± 12.53	0 ± 10.54
Social functioning Cycle 3 Day 28	-1.75 ± 22.15	3.33 ± 13.94
Social functioning Cycle 5 Day 28	5.95 ± 24.98	-2.78 ± 26.70
Social functioning Week 32	0.00 ± 18.26	-6.67 ± 19.00
Social functioning Cycle 11 Day 28	0.00 ± 18.26	0 ± 0
Social functioning Cycle 14 Day 28	0.00 ± 10.54	0 ± 0
Social functioning Cycle 17 Day 28	-4.17 ± 8.33	0 ± 0
Social functioning Cycle 20 Day 28	0 ± 0	0 ± 0
Social functioning Final visit	0.00 ± 30.86	-6.67 ± 25.28
Physical functioning Baseline	86.33 ± 18.92	81.90 ± 11.36
Physical functioning Cycle 2 Day 1	1.48 ± 9.02	2.22 ± 6.89
Physical functioning Cycle 3 Day 28	-2.81 ± 15.45	2.67 ± 5.96
Physical functioning Cycle 5 Day 28	1.43 ± 16.16	-2.22 ± 5.44
Physical functioning Week 32	5.45 ± 15.72	-4.00 ± 7.60
Physical functioning Cycle 11 Day 28	-1.11 ± 6.55	-10.00 ± 14.14
Physical functioning Cycle 14 Day 28	-1.11 ± 2.72	0 ± 9.43
Physical functioning Cycle 17 Day 28	1.67 ± 3.33	0 ± 0
Physical functioning Cycle 20 Day 28	0 ± 0	0 ± 0
Physical functioning Final visit	-4.44 ± 9.65	-2.67 ± 7.60
Global health status/QoL Baseline	61.25 ± 20.28	60.71 ± 7.93
Global health status/QoL Cycle 2 Day 1	2.31 ± 18.92	1.39 ± 8.19
Global health status/QoL Cycle 3 Day 28	7.89 ± 14.56	11.67 ± 9.50
Global health status/QoL Cycle 5 Day 28	7.14 ± 19.84	0 ± 17.48
Global health status/QoL Week 32	9.09 ± 23.41	-8.33 ± 13.18
Global health status/QoL Cycle 11 Day 28	1.39 ± 23.81	8.33 ± 11.79
Global health status/QoL Cycle 14 Day 28	2.78 ± 21.52	8.33 ± 0
Global health status/QoL Cycle 17 Day 28	10.42 ± 20.83	16.67 ± 0
Global health status/QoL Cycle 20 Day 28	25.00 ± 0	25.00 ± 0
Global health status/QoL Final visit	-3.33 ± 23.32	13.33 ± 17.28
Role functioning Baseline	74.17 ± 28.85	76.19 ± 16.27
Role functioning Cycle 2 Day 1	7.41 ± 17.36	-8.33 ± 17.48
Role functioning Cycle 3 Day 28	2.63 ± 17.80	0 ± 11.79
Role functioning Cycle 5 Day 28	7.14 ± 15.63	-2.78 ± 22.15
Role functioning Week 32	15.15 ± 21.67	0 ± 20.41
Role functioning Cycle 11 Day 28	-2.78 ± 19.48	-8.33 ± 11.79
Role functioning Cycle 14 Day 28	5.56 ± 8.61	0 ± 0
Role functioning Cycle 17 Day 28	8.33 ± 9.62	0 ± 0
Role functioning Cycle 20 Day 28	16.67 ± 0	0 ± 0
Role functioning Final Visit	-13.33 ± 32.24	6.67 ± 9.13

Notes
[67] - Only subjects for whom data were collected are included in the analysis.
[68] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Secondary: Frequency Count of Subject Responses to the Patient Global Impression of Change (PGIC) Question Over Time

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End point title

Frequency Count of Subject Responses to the Patient Global Impression of Change (PGIC) Question Over Time

End point description

The PGIC is a one-item measure used to assess perceived treatment benefit. Subjects were be asked "Since the start of the treatment you've received in this study, your polycythemia vera (PV) symptoms are: 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse'. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

End point type

Secondary

End point timeframe

Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

End point values	Ruxolitinib-Naïve Subjects	Ruxolitinib-Resistant or Intolerant Subjects
Number of subjects analysed	20 ^[69]	7 ^[70]
Units: Count of Subjects
number (not applicable)
Cycle 2, Day 1 Very Much Improved	0	0
Cycle 2, Day 1 Much Improved	4	1
Cycle 2, Day 1 Minimally Improved	5	3
Cycle 2, Day 1 No Change	6	1
Cycle 2, Day 1 Minimally Worse	1	1
Cycle 2, Day 1 Much Worse	0	0
Cycle 2, Day 1 Very Much Worse	0	0
Cycle 2, Day 1 Not Assessed	0	1
Cycle 3 Day 28 Very Much Improved	4	1
Cycle 3 Day 28 Much Improved	4	1
Cycle 3 Day 28 Minimally Improved	6	3
Cycle 3 Day 28 No Change	3	0
Cycle 3 Day 28 Minimally Worse	0	0
Cycle 3 Day 28 Much Worse	0	0
Cycle 3 Day 28 Very Much Worse	0	1
Cycle 3 Day 28 Not Assessed	2	1
Cycle 5 Day 28 Very Much Improved	6	1
Cycle 5 Day 28 Much Improved	2	4
Cycle 5 Day 28 Minimally Improved	1	0
Cycle 5 Day 28 No Change	0	0
Cycle 5 Day 28 Minimally Worse	0	0
Cycle 5 Day 28 Much Worse	0	0
Cycle 5 Day 28 Very Much Worse	0	0
Cycle 5 Day 28 Not Assessed	4	0
Week 32 Very Much Improved	3	0
Week 32 Much Improved	3	1
Week 32 Minimally Improved	3	3
Week 32 No Change	1	1
Week 32 Minimally Worse	1	0
Week 32 Much Worse	0	0
Week 32 Very Much Worse	0	0
Week 32 Not Assessed	0	0
Cycle 11 Day 28 Very Much Improved	1	0
Cycle 11 Day 28 Much Improved	3	2
Cycle 11 Day 28 Minimally Improved	0	0
Cycle 11 Day 28 No Change	0	0
Cycle 11 Day 28 Minimally Worse	1	0
Cycle 11 Day 28 Much Worse	0	0
Cycle 11 Day 28 Very Much Worse	0	0
Cycle 11 Day 28 Not Assessed	0	0
Cycle 14 Day 28 Very Much Improved	2	0
Cycle 14 Day 28 Much Improved	2	2
Cycle 14 Day 28 Minimally Improved	0	0
Cycle 14 Day 28 No change	1	0
Cycle 14 Day 28 Minimally Worse	1	0
Cycle 14 Day 28 Much Worse	0	0
Cycle 14 Day 28 Very Much Worse	0	2
Cycle 14 Day 28 Not Assessed	0	0
Cycle 17 Day 28 Very Much Improved	1	0
Cycle 17 Day 28 Much Improved	1	2
Cycle 17 Day 28 Minimally Improved	1	0
Cycle 17 Day 28 No Change	1	0
Cycle 17 Day 28 Minimally Worse	0	0
Cycle 17 Day 28 Much Worse	0	0
Cycle 17 Day 28 Very Much Worse	0	0
Cycle 17 Day 28 Not Assessed	0	0
Cycle 20 Day 28 Very Much Improved	0	0
Cycle 20 Day 28 Much Improved	0	0
Cycle 20 Day 28 Minimally Improved	1	0
Cycle 20 Day 28 No Change	0	0
Cycle 20 Day 28 Minimally Worse	0	0
Cycle 20 Day 28 Much Worse	0	0
Cycle 20 Day 28 Very Much Worse	0	0
Cycle 20 Day 28 Not Assessed	3	1
Final Visit Very Much Improved	3	3
Final Visit Much Improved	2	1
Final Visit Minimally Improved	2	1
Final Visit No Change	6	0
Final Visit Minimally Worse	1	0
Final Visit Much Worse	0	0
Final Visit Very Much Worse	0	0
Final Visit Not Assessed	2	0

Notes
[69] - Only subjects for whom data were collected are included in the analysis.
[70] - Only subjects for whom data were collected are included in the analysis.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline to end of study (up to 2 years) post initial dose or until subject discontinued. Safety follow-up: Until 28 days after the last dose of study treatment or until initiating another anti-cancer therapy.

Adverse event reporting additional description

Reported: Safety Population. During the Safety Follow-up Period, non-Serious Adverse Events occurred at the 5% frequency threshold.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Ruxolitinib-Resistant or Intolerant With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib-Resistant or Intolerant Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib Naive-With Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Reporting group title

Ruxolitinib Naive-Without Splenomegaly

Reporting group description

Subjects received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Serious adverse events	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly	Ruxolitinib Naive-With Splenomegaly	Ruxolitinib Naive-Without Splenomegaly
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	2 / 15 (13.33%)	1 / 5 (20.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Ruxolitinib-Resistant or Intolerant With Splenomegaly	Ruxolitinib-Resistant or Intolerant Without Splenomegaly	Ruxolitinib Naive-With Splenomegaly	Ruxolitinib Naive-Without Splenomegaly
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	1 / 1 (100.00%)	15 / 15 (100.00%)	5 / 5 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	1 / 6 (16.67%)	1 / 1 (100.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	1	0	0
Solitary fibrous tumour
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Vascular disorders
Flushing
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	3	0	0	0
Hot flush
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	2 / 15 (13.33%)	1 / 5 (20.00%)
occurrences all number	4	0	6	2
Chest discomfort
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0
Chest pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Early satiety
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Fatigue
subjects affected / exposed	4 / 6 (66.67%)	1 / 1 (100.00%)	5 / 15 (33.33%)	0 / 5 (0.00%)
occurrences all number	13	3	27	0
Feeling abnormal
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Malaise
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Oedema peripheral
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Pyrexia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0
Breast mass
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Cough
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0
Dyspnoea
subjects affected / exposed	3 / 6 (50.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	3	0	0	0
Dyspnoea at rest
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Hiccups
subjects affected / exposed	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	3	0	0
Nasal congestion
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	1	0	1	1
Wheezing
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Psychiatric disorders
Agitation
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	1
Anxiety
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	1
Confusional state
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Depressed mood
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Depression
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Disorientation
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Hallucination
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Insomnia
subjects affected / exposed	2 / 6 (33.33%)	1 / 1 (100.00%)	2 / 15 (13.33%)	1 / 5 (20.00%)
occurrences all number	3	2	2	1
Irritability
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Libido decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Mood altered
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Thinking abnormal
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Blood creatinine increased
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)
occurrences all number	2	0	4	0
Blood urea increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Platelet count decreased
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	5	0	2	0
White blood cell count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	0	0	1	1
Limb injury
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	0
Rib fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Upper limb fracture
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Wrist fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Cardiac disorders
Extrasystoles
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Palpitations
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Disturbance in attention
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Dizziness
subjects affected / exposed	3 / 6 (50.00%)	0 / 1 (0.00%)	3 / 15 (20.00%)	1 / 5 (20.00%)
occurrences all number	3	0	3	1
Dysgeusia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)
occurrences all number	1	0	9	0
Headache
subjects affected / exposed	3 / 6 (50.00%)	1 / 1 (100.00%)	3 / 15 (20.00%)	1 / 5 (20.00%)
occurrences all number	4	1	4	4
Migraine
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)
occurrences all number	1	0	8	0
Paraesthesia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Parosmia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Seizure
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Somnolence
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Taste disorder
subjects affected / exposed	0 / 6 (0.00%)	1 / 1 (100.00%)	5 / 15 (33.33%)	0 / 5 (0.00%)
occurrences all number	0	4	14	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)
occurrences all number	3	0	3	0
Lymphadenopathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Neutropenia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	3
Thrombocytopenia
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	2	0	0	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Middle ear inflammation
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Tinnitus
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Eye disorders
Dry eye
subjects affected / exposed	1 / 6 (16.67%)	1 / 1 (100.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	1	1	1	0
Ocular hyperaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Photophobia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	2	0	3	2
Abdominal distension
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)
occurrences all number	0	0	5	0
Abdominal pain
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	3 / 15 (20.00%)	1 / 5 (20.00%)
occurrences all number	3	0	4	2
Abdominal pain upper
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	0	0	1	2
Constipation
subjects affected / exposed	3 / 6 (50.00%)	1 / 1 (100.00%)	5 / 15 (33.33%)	0 / 5 (0.00%)
occurrences all number	5	6	7	0
Diarrhoea
subjects affected / exposed	6 / 6 (100.00%)	1 / 1 (100.00%)	11 / 15 (73.33%)	3 / 5 (60.00%)
occurrences all number	9	2	38	11
Dry mouth
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Dyspepsia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)
occurrences all number	0	0	3	0
Flatulence
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)
occurrences all number	0	0	2	0
Gastritis
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Gastrointestinal pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0
Gastrointestinal tract irritation
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Glossitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Hypoaesthesia oral
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	3	0
Irritable bowel syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Mouth ulceration
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Nausea
subjects affected / exposed	6 / 6 (100.00%)	1 / 1 (100.00%)	13 / 15 (86.67%)	5 / 5 (100.00%)
occurrences all number	25	5	60	15
Oral pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Paraesthesia oral
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	3	0
Stomatitis
subjects affected / exposed	3 / 6 (50.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	3	0	0	0
Vomiting
subjects affected / exposed	1 / 6 (16.67%)	1 / 1 (100.00%)	6 / 15 (40.00%)	3 / 5 (60.00%)
occurrences all number	2	1	12	4
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Blister
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Erythema
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Night sweats
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Pruritus
subjects affected / exposed	1 / 6 (16.67%)	1 / 1 (100.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	2	1	1	1
Rash
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 6 (0.00%)	1 / 1 (100.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	1	1	0
Xeroderma
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Pollakiuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	0
Back pain
subjects affected / exposed	3 / 6 (50.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	3	0	2	0
Bone pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Flank pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Pain in extremity
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	4	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	2
Cellulitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Conjunctivitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Sinusitis
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 6 (16.67%)	1 / 1 (100.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	2	0	1
Urinary tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0
Varicella zoster virus infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Appetite disorder
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Decreased appetite
subjects affected / exposed	2 / 6 (33.33%)	0 / 1 (0.00%)	3 / 15 (20.00%)	1 / 5 (20.00%)
occurrences all number	2	0	3	1
Dehydration
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Gout
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	0	0	4	0
Hyperkalaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)
occurrences all number	0	0	1	1
Hyperphosphataemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)
occurrences all number	2	0	1	0
Hyperuricaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 1 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)
occurrences all number	0	0	2	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

01 Jul 2019

Amended to clarify and provide additional detail to allow logistical or pragmatical concerns with the implementation

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 II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Ruxolitinib-Naïve Subjects With Splenomegaly at Baseline who Achieved Composite Response at Week 32

Primary: Percentage of Ruxolitinib-Naïve Subjects With Splenomegaly at Baseline who Achieved Composite Response at Week 32

Primary: Percentage of Ruxolitinib-Naïve Subjects Without Splenomegaly at Baseline who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32

Primary: Percentage of Ruxolitinib-Naïve Subjects Without Splenomegaly at Baseline who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32

Primary: Percentage of All Ruxolitinib-Naïve Subjects (Irrespective of Spleen Size) who Achieved Hct Control Without Phlebotomy at Week 32

Primary: Percentage of All Ruxolitinib-Naïve Subjects (Irrespective of Spleen Size) who Achieved Hct Control Without Phlebotomy at Week 32

Primary: Percentage of All Ruxolitinib-Resistant or Intolerant Subjects who Achieved Hct Control Without Phlebotomy at Week 32

Primary: Percentage of All Ruxolitinib-Resistant or Intolerant Subjects who Achieved Hct Control Without Phlebotomy at Week 32

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Response at Week 32

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Response at Week 32

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Remission at Cycle 11 Day 28

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects who Achieved Complete Hematologic Remission at Cycle 11 Day 28

Secondary: Duration of Complete Hematologic Remission, with a Durable Responder Defined as a Subject in Remission at Week 32 and Cycle 11 Day 28

Secondary: Duration of Complete Hematologic Remission, with a Durable Responder Defined as a Subject in Remission at Week 32 and Cycle 11 Day 28

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline by Response per Modified European Leukemia Net (ELN) Criteria

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline by Response per Modified European Leukemia Net (ELN) Criteria

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline by Response per Modified ELN Criteria

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline by Response per Modified ELN Criteria

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) by Response per Modified ELN Criteria

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) by Response per Modified ELN Criteria

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects With Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects Without Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks from Week 32

Secondary: Duration of Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Duration of Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Subjects (Irrespective of Spleen Size) with Durable Response Lasting at Least 12 Weeks From Week 32

Secondary: Total Number of Subjects With Adverse Events by Severity, Graded According to NCI CTCAE v4.0

Secondary: Total Number of Subjects With Adverse Events by Severity, Graded According to NCI CTCAE v4.0

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Hematology Parameters.

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Hematology Parameters.

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Urinalysis Parameters

Secondary: Percentage of Subjects With Clinical Laboratory Abnormalities: Urinalysis Parameters

Secondary: Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations

Secondary: Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations

Secondary: Change from Baseline in Heart Rate, as Measured by Electrocardiogram

Secondary: Change from Baseline in Heart Rate, as Measured by Electrocardiogram

Secondary: Change from Baseline in Oral Temperature

Secondary: Change from Baseline in Oral Temperature

Secondary: Change from Baseline in Pulse Rate

Secondary: Change from Baseline in Pulse Rate

Secondary: Change from Baseline in Respiratory Rate

Secondary: Change from Baseline in Respiratory Rate

Secondary: Change from Baseline in Systolic Blood Pressure

Secondary: Change from Baseline in Systolic Blood Pressure

Secondary: Change from Baseline in Diastolic Blood Pressure

Secondary: Change from Baseline in Diastolic Blood Pressure

Secondary: Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time

Secondary: Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time

Secondary: Percentage of Subjects With Concomitant Medications

Secondary: Percentage of Subjects With Concomitant Medications

Secondary: Maximum Serum Concentration Observed (Cmax) of Idasanutlin

Secondary: Maximum Serum Concentration Observed (Cmax) of Idasanutlin

Secondary: Trough Concentration (Ctrough) of Idasanutlin

Secondary: Trough Concentration (Ctrough) of Idasanutlin

Secondary: Time of Maximum Concentration Observed (tmax) of Idasanutlin

Secondary: Time of Maximum Concentration Observed (tmax) of Idasanutlin

Secondary: Clearance (CL) of Idasanutlin

Secondary: Clearance (CL) of Idasanutlin

Secondary: Apparent Clearance (CL/F) of Idasanutlin

Secondary: Apparent Clearance (CL/F) of Idasanutlin

Secondary: Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin

Secondary: Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin

Clinical Trial Results:
A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera