Clinical Trial Results:
A Randomized Controlled Phase 3 Study of Oral Pacritinib versus Best Available Therapy in Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis.
Summary
|
|
EudraCT number |
2012-004239-21 |
Trial protocol |
BE GB CZ HU DE IT |
Global end of trial date |
22 Apr 2016
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 Aug 2018
|
First version publication date |
02 Aug 2018
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
PAC325
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01773187 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
CTI Life Sciences Ltd.
|
||
Sponsor organisation address |
Highlands House, Basingstoke Road, Spencers Wood, Reading, Berkshire, United Kingdom, RG7 1NT
|
||
Public contact |
Bruce Seeley Director, CTILS, CTI Life Sciences Ltd., +1 206-272-4260, bseeley@ctibiopharma.com
|
||
Scientific contact |
Bruce Seeley Director, CTILS, CTI Life Sciences Ltd., +1 206-272-4260, bseeley@ctibiopharma.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
30 Jun 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
22 Apr 2016
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the PERSIST-1 study was to compare the efficacy of pacritinib with that of BAT in subjects with PMF, PPV-MF, or PET-MF. The primary efficacy measure for this analysis was the proportion of subjects achieving a ≥35% reduction in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan
|
||
Protection of trial subjects |
This trial was conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines, US FDA regulations 21 Code of Federal Regulations Parts 50, 56, and 312, and with the laws and regulations of the country in which the research was conducted, whichever affords the greatest protection to the study subject.
No trial procedures were performed on trial participants until written consent had been obtained from them. The informed consent form (ICF), protocol, and amendments for this trial were submitted to and approved by the Ethics committee.
Routine monitoring was performed to verify that rights and well being of patients were protected. Also, any medication considered necessary for the patient’s safety and well-being was given at the discretion of the Investigator.
|
||
Background therapy |
The most common concomitant medications by ATC class in the pacritinib and BAT arms, were Antipropulsives (49.1% and 48.1%, respectively), Proton Pump Inhibitors (33.6% and 50.9 %, respectively), Preparations Inhibiting Uric Acid Production (32.7% and 42.5%, respectively), Platelet Aggregation Inhibitors Excluding Heparin (32.7% and 37.7%, respectively), and Anilides (35.0% and 40.6%, respectively). | ||
Evidence for comparator |
The control arm of the study consisted of best available therapies (BAT) , which was the same control arm used in the COMFORT-II phase 3 study of the currently approved JAK2 inhibitor, ruxolitinib. Due to the limitations in the approved indications for ruxolitinib and its regulatory and economic availability on a world-wide basis at the time this study was conducted, ruxolitinib was not included in the BAT treatment arm. Placebo control was deemed inappropriate for these subjects, given the likelihood of efficacy shown in early phase pacritinib clinical studies, as well as the proven efficacy of the approved ruxolitinib agent, which also inhibits the JAK2 pathway. As with the completed phase 3 registrational ruxolitinib COMFORT studies, subjects were permitted to cross over from BAT to pacritinib. This was deemed essential to achieve appropriate equipoise for the participating subjects and to encourage participation given the lack of BAT agents approved for treatment of these MF patients. Crossover provided further scientific benefit as it enabled comparison of safety and efficacy with BAT treatment prior to crossover versus pacritinib treatment after crossover. | ||
Actual start date of recruitment |
08 Jan 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 21
|
||
Country: Number of subjects enrolled |
United Kingdom: 25
|
||
Country: Number of subjects enrolled |
Belgium: 9
|
||
Country: Number of subjects enrolled |
Czech Republic: 18
|
||
Country: Number of subjects enrolled |
France: 35
|
||
Country: Number of subjects enrolled |
Germany: 4
|
||
Country: Number of subjects enrolled |
Hungary: 70
|
||
Country: Number of subjects enrolled |
Italy: 21
|
||
Country: Number of subjects enrolled |
United States: 5
|
||
Country: Number of subjects enrolled |
Russian Federation: 53
|
||
Country: Number of subjects enrolled |
Australia: 46
|
||
Country: Number of subjects enrolled |
New Zealand: 20
|
||
Worldwide total number of subjects |
327
|
||
EEA total number of subjects |
203
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
137
|
||
From 65 to 84 years |
189
|
||
85 years and over |
1
|
|
|||||||||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||||||||
Recruitment details |
327 patients from 12 countries ( 8 EU countries, US, Russia and Australia and New Zealand) were enrolled. Enrolment started on 08 January 2013. Last patient visit was on 22 April 2016. | ||||||||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||||||||
Screening details |
Participants had a washout period (day -35 to day -7) and screening evaluations between day -14 to day -5 before entering treatment. | ||||||||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||||||||
Period 1 title |
overall period
|
||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
Blinding implementation details |
Investigators, site personnel, subjects, clinical monitors, and a designated field CRA were unblinded to individual study treatment assignment. Except certain CTI personnel responsible for pharmacovigilance activities, regulatory submissions, supply chain, and GCP compliance, the sponsor and independent radiographic assessors were blinded throughout the entire study. The sponsor remained blinded to individual study treatment assignment until the database lock for primary analysis.
|
||||||||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||
Arm title
|
Pacritinib | ||||||||||||||||||||||||||||||
Arm description |
Subjects who received pacritinib were to self-administer four 100 mg capsules per day orally, once a day (400 mg daily), at the same time of day, with or without food. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Pacritinib
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Capsule
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
Subjects who received pacritinib were to self-administer four 100 mg capsules per day orally, once a day (400 mg daily), at the same time of day, with or without food.
|
||||||||||||||||||||||||||||||
Arm title
|
Best available Therapies (BAT) | ||||||||||||||||||||||||||||||
Arm description |
Best available Therapies (BAT): Subjects receiving BAT were treated on a schedule commensurate with the therapy(ies) chosen by the investigator. BAT agents could be administered as monotherapy or in combinations, and could be changed (eg, new dose, new schedule, new regimen) as clinically indicated without limitation. Best available therapies may have included any physician-selected treatment for PMF, PPV-MF, or PET-MF, with the exclusion of JAK inhibitors, and may have included any treatment received before study entry. Best available therapies also could have included no treatment (watch and wait) or symptom-directed treatment without MF-specific treatment. BAT therapies could not be co-administered to subjects in the pacritinib arm for treatment of MF. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Hydroxyurea, prednisone, interferon-alpha, thalidomide, danazole, prednisolone, busulfan
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Capsule, Solution for injection, Tablet
|
||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use, Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
BAT agents could be administered as monotherapy or in combinations, and could be changed (eg, new dose, new schedule, new regimen) as clinically indicated without limitation. The pharmaceutical forms and routes of administration depend on the specific product and its clinical indication. Examples of the most used products, their pharmaceutical form and route of administration are shown above.
|
||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pacritinib
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects who received pacritinib were to self-administer four 100 mg capsules per day orally, once a day (400 mg daily), at the same time of day, with or without food. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Best available Therapies (BAT)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Best available Therapies (BAT): Subjects receiving BAT were treated on a schedule commensurate with the therapy(ies) chosen by the investigator. BAT agents could be administered as monotherapy or in combinations, and could be changed (eg, new dose, new schedule, new regimen) as clinically indicated without limitation. Best available therapies may have included any physician-selected treatment for PMF, PPV-MF, or PET-MF, with the exclusion of JAK inhibitors, and may have included any treatment received before study entry. Best available therapies also could have included no treatment (watch and wait) or symptom-directed treatment without MF-specific treatment. BAT therapies could not be co-administered to subjects in the pacritinib arm for treatment of MF. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Pacritinib
|
||
Reporting group description |
Subjects who received pacritinib were to self-administer four 100 mg capsules per day orally, once a day (400 mg daily), at the same time of day, with or without food. | ||
Reporting group title |
Best available Therapies (BAT)
|
||
Reporting group description |
Best available Therapies (BAT): Subjects receiving BAT were treated on a schedule commensurate with the therapy(ies) chosen by the investigator. BAT agents could be administered as monotherapy or in combinations, and could be changed (eg, new dose, new schedule, new regimen) as clinically indicated without limitation. Best available therapies may have included any physician-selected treatment for PMF, PPV-MF, or PET-MF, with the exclusion of JAK inhibitors, and may have included any treatment received before study entry. Best available therapies also could have included no treatment (watch and wait) or symptom-directed treatment without MF-specific treatment. BAT therapies could not be co-administered to subjects in the pacritinib arm for treatment of MF. |
|
|||||||||||||
End point title |
≥35% Spleen Volume Reduction | ||||||||||||
End point description |
The primary efficacy endpoint was the proportion of subjects achieving a ≥35% spleen volume reduction (SVR) from baseline to Week 24, as measured by MRI or CT scan.
For each subject, the same imaging modality was to have been used throughout the study. Splenic progression was followed for subjects who discontinued treatment but did not progress. Subjects with progressive disease documented prior to week 24 who opted to continue on study treatment did not undergo week 24 imaging if the date of progression was at week 20 or later. For subjects who crossed over after week 24, an MRI was done within 30 days prior to the start of pacritinib treatment.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
MRI or CT scan (without contrast agents) was performed prior to randomization (days -10 to -4). MRI or CT scan was performed at the end of week 12 ± 7 days and every 12 weeks thereafter, and at treatment termination.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Primary endpoint statistics | ||||||||||||
Comparison groups |
Pacritinib v Best available Therapies (BAT)
|
||||||||||||
Number of subjects included in analysis |
327
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0003 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
14.1 | ||||||||||||
upper limit |
24.9 |
|
|||||||||||||
End point title |
> 50% TSS reduction on MPN-SAF TSS 2.0 | ||||||||||||
End point description |
The secondary endpoint in the study was the proportion of subjects with a ≥50% reduction from baseline to Week 24 in the subject reported outcome instrument, MPN-SAF TSS 2.0. The original version of this instrument (MPN-SAF TSS) was administered to the first 179 subjects enrolled in the study. However, after discussion with FDA, agreement was reached on modified questions to be included in the instrument. The new version (termed MPN-SAF TSS 2.0) was administered to all subsequently enrolled subjects throughout their participation in the study.
A total of 148 subjects (100 pacritinib, 48 BAT) were tested with the MPN-SAF TSS 2.0 and comprise the ITT population for this endpoint. Responses (on a scale from 0 [absent] to 10 [worst imaginable]) to questions about the symptoms of tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side were used to compute the MPN-SAF TSS 2.0 results.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Daily after receiving eDiary and throughout treatment. Subject-reported symptoms on MPN-SAF TSS 2.0: daily for 7 to 10 consecutive days prior to start of study treatment + daily from day 1 through week 48 or until subject discontinuation.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistics - secondary endpoint | ||||||||||||
Comparison groups |
Best available Therapies (BAT) v Pacritinib
|
||||||||||||
Number of subjects included in analysis |
148
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.2368 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Subjects were evaluated from the time of signing informed consent through 30 d after the last study treatment.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The data display threshold for SAEs is set to 1% or more, that of AEs is set to 5% or more.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pacritinib
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects who received pacritinib were to self-administer four 100 mg capsules per day orally, once a day (400 mg daily), at the same time of day, with or without food. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Best available therapies (BAT) safety population
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subgroup of the ITT population representing subjects who received any dose of study treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
||||||
24 Sep 2012 |
Amendment 1 included the following changes:
- addition of a new inclusion criterion
- addition of dose management guidelines for QTc interval prolongation
- clarification to dose reduction for pacritinib-related, nonhematologic toxicities
- change of timepoints for spleen size assessments. |
||||||
16 Mar 2013 |
Amendment 2 included the following changes:
- revision of secondary and exploratory objectives
- addition of a crossover section from BAT to pacritinib including criteria
- revision of inclusion and exclusion criteria
- addition of a section for withdrawal from study procedures
- revision of the method of treatment assignment
- addition of explanation of QTc calculation and recalculation
- addition of provision of prescription for loperamide (and instructions for use)
- AE section was expanded
- amendment of spleen volume measurement by MRI or CT
- a modified ITT population was added
- the PP population definition was revised
- the Data Monitoring Committee was changed to an IDMC
- major changes to study assessments. |
||||||
15 Aug 2013 |
Amendment 3 included the following changes:
- revision of inclusion and exclusion criteria
- update of statistical methods section
- revision of study design
- revision of period of blinding for independent radiographic assessors
- replacement of MPN-SAF TSS with MPN-SAF TSS 2.0 for subjects randomized under protocol Amendment 3
- revision of the endpoint for collection of AEs and SAEs to the last day of study participation
- amendments and changes to the ITT population
- Major changes to the study assessments. |
||||||
30 Jan 2014 |
Amendment 4 included the following changes:
- revision of sample size of randomized subjects
- revision of statistical methods section
- clarification of PK and PD assessments
- clarification and correction of inconsistencies regarding the timing of the administration of the PGIA, MPN-SAF TSS (all versions), pain medication log, and QoL assessments; clarification regarding use of the MPN-SAF TSS (all versions)
- amendment of timepoints prior to start of study treatment
- revision of the SAE collection time period. |
||||||
21 Feb 2014 |
Amendment 4a:
- revision of sample size of randomized subjects. |
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |