Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label Period to Evaluate the Efficacy and Safety of Fremanezumab for the Prophylactic Treatment of Migraine in Patients With Inadequate Response to Prior Preventive Treatments
Summary
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EudraCT number |
2017-002441-30 |
Trial protocol |
DK GB SE BE DE CZ FI NL ES IT |
Global end of trial date |
29 May 2019
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Results information
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Results version number |
v1 |
This version publication date |
19 Oct 2019
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First version publication date |
19 Oct 2019
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Other versions |
v2 |
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-30068
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03308968 | ||
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 |
41 Moores Road, Frazer, United States, 19355
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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 |
26 Jun 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
29 May 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to demonstrate the efficacy of fremanezumab administered as monthly and quarterly subcutaneous injections to adult participants with migraine with documented inadequate response to 2 to 4 classes of prior preventive treatments as compared with placebo.
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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 good clinical practice 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 |
10 Nov 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: 78
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Country: Number of subjects enrolled |
Sweden: 37
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Country: Number of subjects enrolled |
Switzerland: 2
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Country: Number of subjects enrolled |
United Kingdom: 36
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Country: Number of subjects enrolled |
United States: 120
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Country: Number of subjects enrolled |
Belgium: 50
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Country: Number of subjects enrolled |
Czech Republic: 188
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Country: Number of subjects enrolled |
Denmark: 34
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Country: Number of subjects enrolled |
Finland: 85
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Country: Number of subjects enrolled |
France: 35
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Country: Number of subjects enrolled |
Germany: 74
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Country: Number of subjects enrolled |
Italy: 10
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Country: Number of subjects enrolled |
Netherlands: 23
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Country: Number of subjects enrolled |
Poland: 66
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Worldwide total number of subjects |
838
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EEA total number of subjects |
716
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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) |
807
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From 65 to 84 years |
31
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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 838 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab quarterly, or fremanezumab monthly treatment groups. | ||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Double-Blind Period (12 Weeks)
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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 |
Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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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Arm title
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Fremanezumab Quarterly | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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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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 in pre-filled syringe
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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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Arm title
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Fremanezumab Monthly | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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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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 in pre-filled syringe
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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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Period 2
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Period 2 title |
Open-Label Period (12 Weeks)
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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 Quarterly | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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 Monthly | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
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 in pre-filled syringe
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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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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Quarterly
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Reporting group description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Monthly
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Reporting group description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Reporting group title |
Fremanezumab Quarterly
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Reporting group description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Reporting group title |
Fremanezumab Monthly
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Reporting group description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Reporting group title |
Placebo
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Reporting group description |
Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Reporting group title |
Fremanezumab Quarterly
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Reporting group description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Reporting group title |
Fremanezumab Monthly
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Reporting group description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||
Subject analysis set title |
Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56.
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Subject analysis set title |
Fremanezumab Quarterly
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||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56).
|
||
Subject analysis set title |
Fremanezumab Monthly
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).
|
|
|||||||||||||||||
End point title |
DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A migraine day was defined as when at least 1 of the following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)*28. Change was calculated as post-baseline value – baseline value. DB mITT analysis set: participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on primary endpoint.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||
Statistical analysis description |
Analysis was performed using analysis of covariance (ANCOVA) method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model.
|
||||||||||||||||
Comparison groups |
Placebo v Fremanezumab Quarterly
|
||||||||||||||||
Number of subjects included in analysis |
554
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
Least square (LS) mean difference | ||||||||||||||||
Point estimate |
-3.1
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.84 | ||||||||||||||||
upper limit |
-2.42 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.36
|
||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||
Statistical analysis description |
Analysis was performed using ANCOVA method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model.
|
||||||||||||||||
Comparison groups |
Placebo v Fremanezumab Monthly
|
||||||||||||||||
Number of subjects included in analysis |
561
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-3.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-4.19 | ||||||||||||||||
upper limit |
-2.78 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
0.36
|
|
|||||||||||||||||
End point title |
DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)*28. DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day-1), up to Week 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A headache day of at least moderate severity: a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day demonstrating a headache of any duration that was treated with migraine-specific acute medications. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) * 28. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure(yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects and baseline number of headache days of at least moderate severity and years since onset of migraine as covariates. DB mITT analysis set: participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A migraine day was defined as when at least 1 of following occurred: A calendar day demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with/without aura; at least 4 consecutive hours of a headache meeting criteria for probable migraine; a headache of any duration that was treated with migraine-specific drugs. Monthly averages were derived and normalized to 28 days equivalent by:(number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)*28. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure(yes/no), migraine classification(EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days, years since onset of migraines as covariates. DB mITT analysis set: participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day -1), up to Week 4
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)*28. DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day-1), up to Week 4
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
Baseline data and the mean change from baseline in the monthly average number of days of use of any acute headache medications during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab | ||||||||||||||||
End point description |
A headache day of at least moderate severity: a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day demonstrating a headache of any duration that was treated with migraine-specific acute medications. Monthly averages were derived and normalized to 28 days equivalent by following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) * 28. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of headache days of at least moderate severity and years since onset of migraines as covariates. DB mITT analysis set: participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on primary endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Day -28 to Day -1), up to Week 4
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs | ||||||||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline (Day 0) up to Week 12
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs | ||||||||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal serum chemistry values included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) (units/liter [U/L]): greater than or equal to (≥) 3*upper limit of normal (ULN); Blood Urea Nitrogen (BUN): ≥10.71 millimoles/liter (mmol/L); creatinine: ≥177 micromoles/liter (µmol/L); bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal serum chemistry values included: ALT, AST, ALP, GGT, and LDH (U/L): ≥3*ULN; BUN: ≥10.71 mmol/L; creatinine: ≥177 µmol/L; bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: less than (<) 115 grams/liter (g/L) (in men) or less than or equal to (≤) 95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and absolute neutrophil count (ANC): ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: <115 g/L (in men) or ≤95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and ANC: ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal coagulation values included: prothrombin international normalized ratio (INR): greater than (>) 1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal coagulation values included: prothrombin INR: >1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (milligrams/deciliter [mg/dL]): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (mg/dL): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 beats/minute (bpm) and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 millimeters of mercury (mmHg) and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure: ≤50 mmHg and decrease of ≥15 mmHg or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate: <10 breaths/minute; and body temperature ≥38.3 degrees celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. B safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | ||||||||||||
End point description |
Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 bpm and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 mmHg and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure: ≤50 mmHg and decrease of ≥15 mmHg or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate: <10 breaths/minute; and body temperature ≥38.3 degrees celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 up to Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
DB Period: Number of Participants With Shift From Baseline to Week 12 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 - Week 12 value. Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' = participants with both baseline and Week 12 ECG findings.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
OL Period: Number of Participants With Shift From Baseline to Week 24 in 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 - Week 24 value. Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' = participants with both baseline and Week 24 ECG findings.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 24
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events | ||||||||||||
End point description |
Concomitant medications included: agents acting on the 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, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antipruritics, antipsoriatics, antivirals for systemic use, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, vaccines, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
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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 |
OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events | ||||||||||||
End point description |
Concomitant medications included: agents acting on the 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, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antipruritics, antipsoriatics, antivirals for systemic use, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, vaccines, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
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End point type |
Secondary
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End point timeframe |
Week 12 up to Week 24
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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 (Day 0) up to follow-up visit (Week 46)
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Adverse event reporting additional description |
Safety analysis set: all participants who received at least 1 dose of study drug. AE data were summarized collectively for both periods. 2 participants (1 with CM and 1 with EM) randomized to placebo but received Fremanezumab monthly dosing during double-blind treatment period. They were analyzed in the treatment arm per actual treatment received.
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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 |
DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. OL period: Participants with CM or EM received fremanezumab (TEV-48125) 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Monthly
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Reporting group description |
DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Quarterly
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Reporting group description |
DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: This is a gender-specific AE. Only female participants were at risk. |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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 |