Clinical Trial Results:
A phase I/II, open-label, 2 arm study to investigate the safety, clinical activity, pharmacokinetics and pharmacodynamics of GSK2879552 administered alone or in combination with azacitidine, in adult subjects with IPSS-R high and very high risk myelodysplastic syndromes (MDS) previously treated with hypomethylating agents (HMA)
Summary
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EudraCT number |
2016-002294-35 |
Trial protocol |
ES |
Global end of trial date |
18 Dec 2018
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Results information
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Results version number |
v2(current) |
This version publication date |
09 May 2019
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First version publication date |
01 Mar 2019
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
205744
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Oct 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Dec 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Part I. To determine the recommended phase 2 dose (RP2D) of GSK2879552 administered alone and in combination with azacitidine in adult subjects with HR MDS previously treated with HMA.
Part II. To evaluate clinical activity after treatment with GSK2879552, alone or in combination with azacitidine, in adult subjects with HR MDS previously treated with HMA
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Protection of trial subjects |
Not Applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jul 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
5
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in adult participants with myelodysplastic syndromes (MDS). The study was conducted in 3 centers among 2 countries. | ||||||||||||
Pre-assignment
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Screening details |
Total 5 participants were included into Part 1 and received GSK2879552. The study was terminated during Part 1 and hence Part 2 was not conducted as the risk benefit in earlier studies do not favor continuation of this study. | ||||||||||||
Period 1
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Period 1 title |
Part 1: Dose Confirmation (Upto 2 years) (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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Part 1: GSK2879552 | ||||||||||||
Arm description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
GSK2879552
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
GSK2879552 was administered orally once a day as continuous daily dosing in each cycle (of 28 days) until disease progression.
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Baseline characteristics reporting groups
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Reporting group title |
Part 1: GSK2879552
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Reporting group description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part 1: GSK2879552
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Reporting group description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. | ||
Subject analysis set title |
Part 2: GSK2879552
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
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Subject analysis set title |
Part 2: GSK2879552+Azacitidine
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
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Subject analysis set title |
Part 1: GSK2879552+Azacitidine
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. Participants were also received azacitidine on days 1 to 7 of 28 days cycle via IV or SC administration.
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End point title |
Part 1: Number of participants with any non-serious adverse event (non-SAE), serious AE (SAE), dose limiting toxicities (DLT), dose reductions or delays and withdrawals due to toxicities [1] | ||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.
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End point type |
Primary
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End point timeframe |
Up to 2 years
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [2] - All Treated Subjects Population: All participants who received at least one dose of study treatment. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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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: There are not statistical data to report. |
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Notes [4] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Mean corpuscular volume (MCV) at indicated time-points [5] | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available due to standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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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: There are not statistical data to report. |
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Notes [6] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Mean corpuscular hemoglobin (MCH) at indicated time-points [7] | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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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: There are not statistical data to report. |
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Notes [8] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Mean corpuscular hemoglobin concentration (MCHC) and Hemoglobin (Hb) at indicated time-points [9] | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [10] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Hematocrit at indicated time-points [11] | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [12] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in erythrocytes at indicated time-points [13] | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [14] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in percent reticulocytes at indicated time-points [15] | ||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed.
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [16] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in blast/leukocytes at indicated time-points [17] | ||||||||
End point description |
Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants.
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End point type |
Primary
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End point timeframe |
Baseline and Day 1 of Cycle 1 (Cycle of 28 days)
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Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [18] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Alanine Aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at indicated time-points [19] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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Notes [20] - All Treated Subjects Population. |
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points [21] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
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Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [22] - All Treated Subjects Population. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Part 1: Change from Baseline in Albumin and Protein at indicated time points [23] | ||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||||||||||||||||||||||
Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
Notes [24] - All Treated Subjects Population. |
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Change from Baseline in Partial Pressure Carbon Dioxide (pCO2) at indicated time points [25] | ||||||||
End point description |
Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline and Day 1 of Cycle 1 (cycle of 28 days)
|
||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||
|
|||||||||
Notes [26] - All Treated Subjects Population. |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Part 1: Change from Baseline in Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time-points [27] | ||||||||||||||||||||||||||||||||
End point description |
Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||||||||||||||
Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [28] - All Treated Subjects Population. |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Part 1: Change from Baseline in heart rate at indicated time-points [29] | ||||||||||||||||||||
End point description |
Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||
Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [30] - All Treated Subjects Population. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Part 1: Change from Baseline in respiratory rate at indicated time-points [31] | ||||||||||||||||||||
End point description |
Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [32] - All Treated Subjects Population. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Part 1: Change from Baseline in body temperature at indicated time-points [33] | ||||||||||||||||||||
End point description |
Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||
Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [34] - All Treated Subjects Population. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Part 1: Change from Baseline in electrocardiogram (ECG) mean heart rate at indicated time-points [35] | ||||||||||||||||||||
End point description |
Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 1,7), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||
Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [36] - All Treated Subjects Population. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Part 1: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF) at indicated time-points [37] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1 (Days 1,7), Cycle 2 (Days 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [38] - All Treated Subjects Population. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Part 1: Number of participants with abnormal findings during physical examination [39] | ||||||
End point description |
A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant. This analysis was planned but data was not captured in the database.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
Up to 2 years
|
||||||
Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||
|
|||||||
Notes [40] - All Treated Subjects Population. |
|||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Percentage of participants with investigator-assessed best response assessed by Clinical Benefit Rate (CBR) [41] | ||||||||||||
End point description |
CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
Notes [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [42] - All Treated Subjects Population. [43] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Percentage of participants with investigator-assessed best response assessed by Objective Response Rate (ORR) [44] | ||||||||||||
End point description |
Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
Notes [44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [45] - All Treated Subjects Population. [46] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Part 1: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points [47] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are not statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [48] - All Treated Subjects Population. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Percentage of participants with investigator-assessed best response assessed by Clinical Benefit Rate (CBR) | ||||||||
End point description |
CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [49] - All Treated Subjects Population. |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Percentage of participants with investigator-assessed best response assessed by Objective Response Rate (ORR) | ||||||||
End point description |
ORR was defined as the percentage of participants who achieved Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [50] - All Treated Subjects Population. |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Part 1: Plasma concentration of GSK2879552 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood samples for pharmacokinetics were obtained and analyzed. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. For Cycle 1, Day 1, pre-dose, all concentration values were less than the lower limit of quantification, therefore they have been imputed with 0 because they were so small. Hence, standard deviation was not calculated as it would result to “0” and would be misleading. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [51] - PK Concentration Population. |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Plasma concentration of Azacitidine | ||||||||
End point description |
Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine. Data was not collected due to blood samples were not collected as participants were not enrolled in GSK2879552 + Azacitidine arm due to early termination of the study.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)
|
||||||||
|
|||||||||
Notes [52] - PK Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Duration of Response | ||||||||
End point description |
Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment. Data was not collected for this endpoint as DOR could not be calculated because of the early termination of the study did not allow for this endpoint to be observed.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [53] - All Treated Subjects Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Progression-free Survival | ||||||||
End point description |
Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [54] - All Treated Subjects Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Overall Survival | ||||||||
End point description |
Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), the last date of known contact was used for those participants who had not died at the time of analysis; such participants were considered censored. 99999 indicates data was not available as the data and very small number of subjects do not allow meaningful calculation of the upper limit of 95% CI.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [55] - All Treated Subjects Population |
|||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Part 1: Proportion of participants with disease progression to Acute Myeloblastic Leukemia (AML) | ||||||
End point description |
The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Up to 2 years
|
||||||
|
|||||||
Notes [56] - All Treated Subjects Population |
|||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Part 1: Time to AML progression | ||||||||
End point description |
Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 2 years
|
||||||||
|
|||||||||
Notes [57] - All Treated Subjects Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 1: Number of participants with documented platelet and red blood cell (RBC) transfusions per month | ||||||||||||
End point description |
Number of participants with documented platelet and RBC transfusions have been presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 2 years
|
||||||||||||
|
|||||||||||||
Notes [58] - All Treated Subjects Population |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Part 2: Number of participants with any AEs and SAEs | |||||||||
End point description |
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. All Treated Subject Population was defined as all participants who received at least one dose of study treatment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 2.5 years
|
|||||||||
|
||||||||||
Notes [59] - All Treated Subjects Population. [60] - All Treated Subjects Population. |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [61] - All Treated Subjects Population. [62] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in MCV at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [63] - All Treated Subjects Population. [64] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in MCH at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [65] - All Treated Subjects Population. [66] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in MCHC and Hb at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [67] - All Treated Subjects Population. [68] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in Hematocrit at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [69] - All Treated Subjects Population. [70] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in erythrocytes at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [71] - All Treated Subjects Population. [72] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in percent reticulocytes at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [73] - All Treated Subjects Population. [74] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in blast/leukocytes at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [75] - All Treated Subjects Population. [76] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in ALT, ALP, AST, LDH and GGT at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [77] - All Treated Subjects Population. [78] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [79] - All Treated Subjects Population. [80] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [81] - All Treated Subjects Population. [82] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in Albumin and Protein at indicated time points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [83] - All Treated Subjects Population. [84] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in pCO2 at indicated time points | ||||||||||||
End point description |
Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [85] - All Treated Subjects Population. [86] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in SBP and DBP at indicated time-points | ||||||||||||
End point description |
Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [87] - All Treated Subjects Population. [88] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in heart rate at indicated time-points | ||||||||||||
End point description |
Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [89] - All Treated Subjects Population. [90] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in respiratory rate at indicated time-points | ||||||||||||
End point description |
Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [91] - All Treated Subjects Population. [92] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in body temperature at indicated time-points | ||||||||||||
End point description |
Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [93] - All Treated Subjects Population. [94] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in ECG mean heart rate at indicated time-points | ||||||||||||
End point description |
Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [95] - All Treated Subjects Population. [96] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time-points | ||||||||||||
End point description |
Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [97] - All Treated Subjects Population. [98] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Part 2: Number of participants with abnormal findings during physical examination | |||||||||
End point description |
A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 2.5 years
|
|||||||||
|
||||||||||
Notes [99] - All Treated Subjects Population. [100] - All Treated Subjects Population. |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Plasma clearance (CL/F) of GSK2879552 | ||||||||||||
End point description |
Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)
|
||||||||||||
|
|||||||||||||
Notes [101] - PK Concentration Population. [102] - PK Concentration Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Duration of Response | ||||||||||||
End point description |
Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [103] - All Treated Subjects Population. [104] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Progression-free Survival | ||||||||||||
End point description |
Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [105] - All Treated Subjects Population. [106] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Overall Survival | ||||||||||||
End point description |
Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [107] - All Treated Subjects Population. [108] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Part 2: Percentage of participants with disease progression to AML | |||||||||
End point description |
The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 2.5 years
|
|||||||||
|
||||||||||
Notes [109] - All Treated Subjects Population. [110] - All Treated Subjects Population. |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Part 2: Time to AML progression | ||||||||||||
End point description |
Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 2.5 years
|
||||||||||||
|
|||||||||||||
Notes [111] - All Treated Subjects Population. [112] - All Treated Subjects Population. |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Part 2: Number of participants with documented platelet and red blood cell (RBC) transfusions per month | |||||||||
End point description |
Number of participants with documented platelet and RBC transfusions were to be presented. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 2.5 years
|
|||||||||
|
||||||||||
Notes [113] - All Treated Subjects Population. [114] - All Treated Subjects Population. |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Serious adverse events (SAEs) and Non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to Cycle 5 (each cycle of 28 days) in Part 1.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
SAEs and Non-SAEs were reported by treatment for the All Treated Subjects Population which comprised of all participants who received at least one dose of study treatment. Data is presented for Part 1 only as data was not collected in Part 2 due to the study was terminated during Part 1 only, and Part 2 was not initiated.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 1: GSK2879552
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 May 2017 |
Amendment No. 1: Addition of language to include a stopping rule that halts enrollment upon the occurrence
of any encephalopathy, unless clearly attributable to central nervous system disease involvement or intercurrent illness. Minor clarifications, correction of typographical errors, reformatting of tables, administrative and grammatical changes to text and Time and Events tables/footnotes. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |