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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Telcagepant
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telcagepant<br>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<br>* Telcagepant 140 mg film coated tablet for oral administration<br>* Other names: MK-0974;|
| Placebo Comparator: Placebo<br>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<br>* Placebo to match telcagepant 140 mg film coated tablet for oral administration<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Menstrually related migraine, migraine, Premenstrual migraine