Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV-48125 Versus Placebo for the Prevention of Episodic Cluster Headache
Summary
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EudraCT number |
2016-003278-42 |
Trial protocol |
GB SE DE ES IT NL PL FI |
Global end of trial date |
13 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
01 May 2020
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First version publication date |
01 May 2020
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Other versions |
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 |
TV48125-CNS-30056
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02945046 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products, R&D Inc.
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Sponsor organisation address |
145 Brandywine Parkway, West Chester, United States, 19380
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 8884838279, info.eraclinical@teva.de
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 8884838279, info.eraclinical@teva.de
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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 |
27 Jun 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 May 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
13 May 2019
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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 |
The primary objective of this study was to demonstrate the efficacy of fremanezumab in the prevention of episodic cluster headache (ECH) in adult participants.
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Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (for example, Code of Federal Regulations Title 21, Parts 50, 54, 56, 312, and 314; European Union Directive 2001/20/EC on the approximation of the laws, regulations, and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jan 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 |
Australia: 1
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Finland: 7
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Israel: 25
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Country: Number of subjects enrolled |
Italy: 44
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Country: Number of subjects enrolled |
Poland: 6
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Country: Number of subjects enrolled |
Sweden: 5
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Country: Number of subjects enrolled |
United States: 61
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Worldwide total number of subjects |
169
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EEA total number of subjects |
80
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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) |
164
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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 |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 169 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab 675 milligrams (mg)/placebo/placebo, or fremanezumab 900/225/225 mg groups. | ||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
Placebo matched to fremanezumab was administered per schedule specified in the arm.
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Arm title
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Fremanezumab 675 mg/Placebo/Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use, Intravenous use
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Dosage and administration details |
Placebo matched to fremanezumab was administered per schedule specified in the arm.
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Investigational medicinal product name |
Fremanezumab
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Investigational medicinal product code |
TEV-48125
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Fremanezumab was administered per dose and schedule specified in the arm.
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Arm title
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Fremanezumab 900/225/225 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo matched to fremanezumab was administered per schedule specified in the arm.
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Investigational medicinal product name |
Fremanezumab
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Investigational medicinal product code |
TEV-48125
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use, Intravenous use
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Dosage and administration details |
Fremanezumab was administered per dose and schedule specified in the arm.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab 675 mg/Placebo/Placebo
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Reporting group description |
Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab 900/225/225 mg
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Reporting group description |
Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively. | ||
Reporting group title |
Fremanezumab 675 mg/Placebo/Placebo
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Reporting group description |
Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | ||
Reporting group title |
Fremanezumab 900/225/225 mg
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Reporting group description |
Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. |
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End point title |
Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP | ||||||||||||||||
End point description |
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States [US]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Primary
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End point timeframe |
Baseline (Week 0), up to Week 4
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||
Comparison groups |
Fremanezumab 675 mg/Placebo/Placebo v Placebo
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Number of subjects included in analysis |
110
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||
P-value |
= 0.9093 [1] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-0.1
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-2.72 | ||||||||||||||||
upper limit |
2.42 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.3
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Notes [1] - Threshold for significance at 0.05 level. |
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||
Comparison groups |
Fremanezumab 900/225/225 mg v Placebo
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Number of subjects included in analysis |
112
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||
P-value |
= 0.1345 [2] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-1.9
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-4.49 | ||||||||||||||||
upper limit |
0.61 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.29
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Notes [2] - Threshold for significance at 0.05 level. |
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End point title |
Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP | ||||||||||||
End point description |
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), up to Week 4
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP | ||||||||||||||||
End point description |
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using mixed model for repeated measures (MMRM) with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), up to Week 12
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP | ||||||||||||||||
End point description |
CH attack: a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of following 2 categories: 1) at least 1 of following symptoms/signs, ipsilateral to headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using MMRM with baseline preventive medication use (yes/no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Full analysis set: all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in first 4 weeks on primary endpoint. Here, 'overall number of participants analyzed'=participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), Week 8 up to Week 12
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline in the Weekly Average Number of Days with Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP | ||||||||||||||||
End point description |
A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), up to Week 12
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline in the Weekly Average Number of Days Oxygen was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP | ||||||||||||||||
End point description |
LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat ECH during the 12-week period after administration of the first dose of IMP (based on Week 0 to 12 data) is reported. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is “1=much worse,” “2=moderately worse,” “3=slightly worse,” “4=unchanged,” “5=slightly improved,” “6=moderately improved,” or “7=much improved” compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of “5=slightly improved.” Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early. Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 1, 4, 8, and 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Adverse Events (AEs) | ||||||||||||||||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants with Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | ||||||||||||||||||||||||
End point description |
Serum chemistry, hematology, urinalysis tests with potentially clinically significant abnormal findings: alanine aminotransferase (ALP), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) each ≥3*upper limit of normal(ULN); blood urea nitrogen ≥10.71 millimole (mmol)/L; Bilirubin ≥34.2 micromole/liter (umol/L); creatinine ≥177 umol/L; hemoglobin ≤115 grams(g)/L (males) or ≤95 g/L (females); leukocytes ≥20*10^9/L or ≤3*10^9/L; eosinophils ≥10%; hematocrit <0.37 L/L (males) and <0.32 L/L (females); platelets ≥700*10^9/L or ≤75*10^9/L; haemoglobin, urine glucose, ketones, total protein each ≥2 unit(U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set: all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | ||||||||||||
End point description |
Potentially clinically significant abnormal vital signs findings included: pulse rate ≥120 beats per minute (bpm) and increase of 15 bpm; systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease of 20 mmHg; diastolic blood pressure ≤50 mmHg and decrease of 15 mmHg, or ≥105 mmHg and increase of 15 mmHg. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
|
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants Who Received Concomitant Medications | ||||||||||||
End point description |
Concomitant medications included: agents acting on renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihypertensives, antiinflammatory and antirheumatic products, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
|
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Injection Site Reactions | ||||||||||||||||||||||||||||||||||||
End point description |
Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, swelling, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Hypersensitivity/Anaphylaxis Reactions | ||||||||||||
End point description |
A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
|
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | ||||||||||||
End point description |
eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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End point type |
Secondary
|
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End point timeframe |
Baseline up to Week 12
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 12
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Adverse event reporting additional description |
Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab 675 mg/Placebo/Placebo
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Reporting group description |
Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab 900/225/225 mg
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Reporting group description |
Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
01 May 2017 |
The following major procedural changes (not all inclusive) were made to the protocol:
- Clarification was provided based on feedback from participating investigators and regulatory agencies.
- Table (Study Procedures and Assessments) was revised. |
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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. | |||
Study was terminated as a result of a pre-specified futility analysis at the interim of 150 participants completing the efficacy analysis of the study. |