A Multicenter Study to Evaluate the Efficacy of a 91-Day Extended Cycle Oral Contraceptive for Menstrually-Related Migraine Headaches

Study Overview
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Brief Summary
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This study is being conducted to evaluate the efficacy of a 91-day extended cycle oral contraceptive compared to placebo for decreasing the frequency and severity of menstrually-related migraine headaches.

Official Title
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A Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy of DR-105 Compared to Placebo For the Management of Menstrually-Related Migraine Headaches.

Conditions
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Migraine

Intervention / Treatment
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* Drug: 91-day Levonorgestrel Oral Contraceptive
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal, non-pregnant, non-lactating History of migraine headaches without aura for at least 6 months History of migraine headaches associated with menstruation Others as directed by FDA-approved protocol Exclusion Criteria: History of migraine headaches with aura or focal neurological symptoms Any contraindication to the use of oral contraceptives Others as dictated by FDA-approved protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 91-day Levonorgestrel Oral Contraceptive<br>Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks. | Drug: 91-day Levonorgestrel Oral Contraceptive<br>* 91-day treatment consisting of 84 blue combination tablets containing 150 µg LNG/30 µg EE and 7 yellow tablets containing 10 µg EE.<br>* Other names: DR-105;|
| Placebo Comparator: Placebo<br>Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks. | Drug: Placebo<br>* 1 tablet daily to match experimental arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the Treatment Period | The number of participants with at least 50% reduction in migraine frequency (average weekly number of migraine episodes) through the end of the 91-day treatment period compared with Baseline (the 25- to 35-day baseline qualification period). Participants recorded the incidence, timing and intensity of migraines in a migraine diary during the prequalification period and throughout the 91-day treatment period. | Baseline (25-35 days before Day 1) and Days 1-91 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the First, Second and Third Months | The percentage of participants with at least 50% reduction in migraine frequency (average weekly number of migraine episodes) compared to Baseline at each month of the treatment period. | Baseline, Month1, Month 2 and Month 3 | 
| Change From Baseline in Average Migraine Severity | Migraine severity was recorded by participants in the Baseline qualification diary and study migraine diary during the treatment period. Participants could report a severity of none (score = 0), mild (1), moderate (2), or severe (3). In general, if a headache was mild, daily activities could be resumed and little to no medication was taken. Moderate headaches required medication and effected daily activities. Severe headaches were debilitating and required medication. Average migraine severity is defined as the sum of the severity ratings divided by the total number of migraine episodes reported during the observation period (for example, Baseline, First Month, Second Month, Third Month, and 91-Day Treatment Period). A negative change from Baseline score indicates improvement in severity. | Baseline and Month 1, Month 2 and Month 3 | 
| Percentage of Participants Who Required Rescue Medications During the Study Period | Participants recorded use of rescue medications for migraines in the migraine diary during the course of study treatment. | Baseline, Month 1, Month 2 and Month 3 | 
| Change From Baseline in Migraine Disability Assessment | The migraine disability assessment (MIDAS) test is used to determine how severely migraines affect a patient's life. Participants were asked five questions about how often their headaches limited their ability to go to work or school, to do household work or to do family or leisure activities in the past 3 months. The MIDAS score equals the sum of the days answered for each question and ranges from 0 (no disability) to approximately 270 (severe disability; the upper bound is dependent on the number of days a participant would plan to work or participate in other activities). The MIDAS score is classified into four grades of severity: 0 to 5: MIDAS Grade I, Little or no disability 6 to 10: MIDAS Grade II, Mild disability 11 to 20: MIDAS Grade III, Moderate disability 21+: MIDAS Grade IV, Severe disability | Baseline and Week 15 | 
| Change From Baseline in Headache Impact Test | The Headache Impact Test (HIT) is a tool used to measure the impact headaches have on patients' ability to function on the job, at school, at home and in social situations. HIT-6 consists of 6 questions each scored on a scale from Never (6 points) to Always (13 points). The total score ranges from 36 to 78 with higher scores indicating greater impact on life. There was an error in administration of the HIT-6 in this study. Question 6 was not administered, and question 3 from the MIDAS was included instead. Therefore, the total score of the HIT-6 could not be calculated. | Baseline and Week 15 | 
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical investigation participant and which does not necessarily have to have a causal relationship with this treatment or clinical study. The following definitions were used to assess AE severity: Mild: Awareness of signs or symptoms, but they are easily tolerated; Moderate: Enough discomfort to cause interference with usual activity; Severe: Incapacitating, with inability to perform usual activity. Relationship to study drug was assessed as either: None: Causal relationship can be ruled out; Possibly: Causal relationship at least reasonably possible, i.e. relationship cannot be ruled out; Definitely: Causal relationship is certain. A serious adverse event (SAE) is one that met any one of the following criteria: Fatal or life threatening Requires or prolongs in patient hospitalization Results in persistent or significant disability/incapacity Congenital anomaly / birth defect Important medical event. | Up to 15 weeks | 
| Mean Number of Days of Bleeding or Spotting | Bleeding and spotting were recorded by participants in the migraine diary during the 91-day treatment period. | 91-day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine headache, menstrual, oral contraceptive, Menstrually-Related Migraine Headache