Telcagepant for Prevention of Menstrually Related Migraine in Female Participants With Episodic Migraine (MK-0974-065)

A Six Month Phase II/III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of Telcagepant (MK-0974) for Prevention of Menstrually Related Migraine in Female Patients With Episodic Migraine

This is a multicenter study to test the hypothesis that telcagepant is superior to placebo in preventing perimenstrual migraines as measured by mean monthly headaches during the entire treatment period. This study will also evaluate the safety and tolerability of telcagepant for female migraine participants.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Telcagepant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 4548
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant who has had regular menstrual cycles monthly (22 to 32 days) for at least the last 3 cycles
• Participant experiences headache during menstrual period in at least 2 out of last 3 cycles
• Participant has history of migraine for ≥ 3 months and with ≥ 2 migraine attacks per month in the 2 months prior to screening
• Participant agrees to use an effective method of birth control through the duration of the study

Exclusion Criteria:

• Participant has basilar or hemiplegic migraine headache
• Participant has taken medication for acute headache on more than 15 days per month in the 3 months prior to screening
• Participant is taking prophylactic medication for migraine and daily dose has changed within 4 weeks prior to screening
• Participant has history of significant liver disease
• Participant has had cardiac surgery or symptoms within 3 months of screening
• Participant has confounding pain syndromes, psychiatric conditions, dementia, or major neurological disorders other than migraine
• Participant has history of neoplastic disease ≤ 5 years prior to signing informed consent
• Participant has history of gastric or small intestinal surgery
• Participant consumes 3 or more alcoholic drinks per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telcagepant; Telcagepant 140 mg was administered once daily at bedtime for 7 consecutive days each month, beginning at the onset of menses, for up to 6 months. Dosing could begin up to 3 days prior to menses onset if prodromal symptoms reliably predicted onset of menses.	Drug: Telcagepant; Telcagepant 140 mg film coated tablet for oral administration; Other Names: MK-0974
Placebo Comparator: Placebo; Placebo was administered once daily at bedtime for 7 consecutive days each month, beginning at the onset of menses, for up to 6 months. Dosing could begin up to 3 days prior to menses onset if prodromal symptoms reliably predicted onset of menses.	Drug: Placebo; Placebo to match telcagepant 140 mg film coated tablet for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Adverse Events (AEs)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE. A clinical AE is an AE reported as a result of a clinical examination or reported by the participant.	Up to 14 days after the last dose of study drug (Up to 6.5 months)
Number of Participants Who Discontinued Study Due to a Clinical AE	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE. A clinical AE is an AE reported as a result of a clinical examination or reported by the participant.	Up to 6 months
Number of Participants With Laboratory AEs	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE. A laboratory AE is an AE reported as a result of a laboratory assessment or test.	Up to 6 months
Number of Participants Who Discontinued Study Due to a Laboratory AE	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE. A laboratory AE is an AE reported as a result of a laboratory assessment or test.	Up to 6 months
Mean Monthly Headache Days During Entire Study Period Among Participants With Menstrually-related Migraine (MRM) or Pure Menstrual Migraine (PMM) Who Have an Average of 5 or More Moderate or Severe Migraine Headaches Per Month at Baseline	Participants completed a headache diary each evening at bedtime, including recording headache duration and acute headache medication use. Mean monthly headache days was calculated from diary data. A headache day was defined as a day in which a headache (defined as headache pain ≥30 minute duration or requiring acute treatment) started, ended, or recurred. Headache pain persisting for more than 1 calendar day after initial onset was considered an occurrence of additional headache days. Mean monthly rate was adjusted to 28 days. Participant subgroups (based on symptoms over the 3 menstrual cycles prior to study): PMM - In ≥2 out of 3 cycles attacks occur exclusively on Day 1 ± 2 of menstruation and at no other times of the cycle; MRM - In ≥2 out of 3 cycles attacks occur on Day 1 ± 2 of menstruation and additionally at other times of the cycle.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Monthly Headache Days During Entire Study Period Among Participants With MRM Who Have an Average of 5 or More Moderate or Severe Migraine Headaches Per Month at Baseline	Participants completed a headache diary each evening at bedtime, including recording headache duration and acute headache medication use. Mean monthly headache days was calculated from diary data. A headache day was defined as a day in which a headache (defined as headache pain ≥30 minute duration or requiring acute treatment) started, ended, or recurred. Headache pain persisting for more than 1 calendar day after initial onset was considered an occurrence of additional headache days. Mean monthly rate was adjusted to 28 days. MRM participant subgroup (based on symptoms over the 3 menstrual cycles prior to study) - In ≥2 out of 3 cycles attacks occur on Day 1 ± 2 of menstruation and additionally at other times of the cycle.	Up to 6 months
Mean Monthly On-drug Headache Days During the Entire Study Period Among Participants With MRM or PMM Who Have an Average of 5 or More Moderate or Severe Migraine Headaches Per Month at Baseline	Participants completed a headache diary each evening at bedtime, including recording headache duration and acute headache medication use. Mean monthly on-drug headache days was calculated from diary data. "On-drug" headache day was a day, which had a valid diary entry and which followed a study drug dosing day, in which a headache (defined as headache pain ≥30 minute duration or requiring acute treatment) started, ended, or recurred. Headache pain persisting for more than 1 calendar day after initial onset into additional qualifying days (i.e., day following dosing day) was considered an occurrence of additional headache days. Mean monthly rate was adjusted to 7 days. Participant subgroups (based on symptoms over the 3 menstrual cycles prior to study): PMM - In ≥2 out of 3 cycles attacks occur exclusively on Day 1 ± 2 of menstruation and at no other times of the cycle; MRM - In ≥2 out of 3 cycles attacks occur on Day 1 ± 2 of menstruation and additionally at other times of the cycle.	Up to 6 months
Mean Monthly On-drug Headache Days During the Entire Study Period Among Participants With MRM Who Have an Average of 5 or More Moderate or Severe Migraine Headaches Per Month at Baseline	Participants completed a headache diary each evening at bedtime, including recording headache duration and acute headache medication use. Mean monthly on-drug headache days was calculated from diary data. "On-drug" headache day was a day, which had a valid diary entry and which followed a study drug dosing day, in which a headache (defined as headache pain ≥30 minute duration or requiring acute treatment) started, ended, or recurred. Headache pain persisting for more than 1 calendar day after initial onset into additional qualifying days (i.e., day following dosing day) was considered an occurrence of additional headache days. Mean monthly rate was adjusted to 7 days. MRM participant subgroup (based on symptoms over the 3 menstrual cycles prior to study) - In ≥2 out of 3 cycles attacks occur on Day 1 ± 2 of menstruation additionally at other times of the cycle.	Up to 6 months
Mean Monthly On-drug Headache Days During the Entire Study Period Among Participants With PMM Who Have an Average of 3 or More Moderate or Severe Migraine Headaches Per Month at Baseline	Participants completed a headache diary each evening at bedtime, including recording headache duration and acute headache medication use. Mean monthly on-drug headache days was calculated from diary data. "On-drug" headache day was a day, which had a valid diary entry and which followed a study drug dosing day, in which a headache (defined as headache pain ≥30 minute duration or requiring acute treatment) started, ended, or recurred. Headache pain persisting for more than 1 calendar day after initial onset into additional qualifying days (i.e., day following dosing day) was considered an occurrence of additional headache days. Mean monthly rate was adjusted to 7 days. PMM participant subgroups (based on symptoms over the 3 menstrual cycles prior to study) - In ≥2 out of 3 cycles attacks occur exclusively on Day 1 ± 2 of menstruation and at no other times of the cycle.	Up to 6 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ho TW, Ho AP, Ge YJ, Assaid C, Gottwald R, MacGregor EA, Mannix LK, van Oosterhout WP, Koppenhaver J, Lines C, Ferrari MD, Michelson D. Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine. Cephalalgia. 2016 Feb;36(2):148-61. doi: 10.1177/0333102415584308. Epub 2015 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): April 8, 2011
• Study Completion (Actual): April 8, 2011

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (Estimate): May 18, 2010

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: migraine; Menstrually related migraine; Premenstrual migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 0974-065; 2010_535 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis