Clinical trial NCT01035983: Safety and Tolerability of Frovatriptan to Prevention of Menstrually Associated Migraine (MAM) Headaches
Official title: An Open Label Study to Assess the Safety, Tolerability and Efficacy of Frovatriptan in the Prevention of Menstrually Associated Migraine (MAM) Headaches.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Keywords: menstrually associated migraine (MAM), Migraines,Menstrual Migraines, menstrually related migraines
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Vernalis (R&D) Ltd
First posted: 2009-12-21
Enrollment: 550
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this open-label, multi-center study, patients were treated with frovatriptan for a maximum of 12 perimenstrual periods (PMPs). For each PMP, dosing commenced 2 days before the anticipated onset of the menstrual migraine (MM) headache and continued for a total of 6 days. Patients were to take a loading dose of frovatriptan 5 mg (two tablets) twice daily on Day 1, followed by frovatriptan 2.5 mg twice daily on Days 2-6. During the study, patients were to visit the study site a total of 6 times. Efficacy and/or safety assessments were performed at each visit.

Detailed description: This Phase IIIb, open label, multi-centre study evaluated the safety and tolerability of frovatriptan taken by patients for up to 12 perimenstrual periods (PMPs) for the prevention of menstrual migraine (MM). The study required approximately 300 patients to treat 6 PMPs and 100 patients to treat 12 PMPs. To achieve these numbers, 550 patients were to be enrolled into the study. Once enrolled, patients were requested to treat at least 6 PMPs in the first 9 months and 12 PMPs overall. Patients were to remain in the study for a maximum of 15 months or until they had completed the treatment of 12 PMPs, whichever occurred sooner.Patients were to take a loading dose of frovatriptan 5 mg (two tablets) twice daily on Day 1, followed by frovatriptan 2.5 mg twice daily on Days 2-6.

Eligibility criteria: Inclusion Criteria:

* Female aged 15 years and over (≥18 years in United Kingdom and South Africa), with at least a 12 month documented history of experiencing migraine according to IHS criteria, including confirmation of a 3 month diary based documented history of MAM.
* An average frequency of MAM in at least two out of three menstrual cycles, within the previous 12 months
* Regular, predictable menstrual periods
* MAM headaches occurring between Day -2 and day +4 of menses
* Able and willing to sign informed consent and to comply with study procedures, including completion of the diary cards.

Exclusion Criteria:

* More than three migraine attacks per month that were not MAM attacks
* A history of myocardial infarction, ischemic heart disease (or presenting with symptoms or signs compatible with ischemic heart disease), coronary vasospasm or peripheral vascular disease
* Significant cerebrovascular disease including basilar or hemiplegic migraine
* Uncontrolled hypertension (SBP \>180 mmHg, DBP \>95 mmHg)
* Severe hepatic or renal insufficiency
* More than 15 headache days per month, exclusive of migraine headache
* Any other condition or serious illness which, in the opinion of the investigator, would interfere with optimal participation in the study
* A history of clinically relevant allergy, including that to frovatriptan or other triptans
* Pregnant or breast-feeding, or intending to become pregnant or breast-feed during the study period (patients were to be using adequate contraception and have a negative pregnancy test at screening)
* Treatment with another investigational drug within 30 days or 5 half-lives (whichever was longer) before the screening visit
* Any change in their oral contraceptive medication (if applicable) in the 2 months prior to screening, or anticipation of any change during study participation
* Any change in the type or dose of any prophylactic migraine medication in the 2 months prior to screening, or anticipation of any change during study participation
* A history of migraine with aura, according to IHS criteria, and currently treated with a combined oral contraceptive (South Africa only).

Primary outcomes:
measure: Incidence of all treatment-emergent adverse events (AEs).
timeFrame: 9-15 months
Secondary outcomes:
measure: Incidence of menstrual migraine headache
timeFrame: 9-15 months
measure: Maximum headache severity
timeFrame: 9-15 months
measure: Number of headache-free days during a treated perimenstrual period (PMP)
timeFrame: 9-15 months
measure: Occurrence and severity of menstrual migraine headache-associated symptoms
timeFrame: 9-15 months
measure: Maximum functional impairment during menstrual migraine headache
timeFrame: 9-15 months
measure: Incidence and severity of intercurrent migraine
timeFrame: 9-15 months
measure: Total migraine burden
timeFrame: 9-15 months
measure: Standard hematology and biochemistry
timeFrame: 9-15 months
measure: 12-lead electrocardiogram (ECG) and vital signs, physical examination
timeFrame: 9-15 months
measure: Short-form 12 (SF-12) Health Related Quality of Life Questionnaire
timeFrame: 9-12 months
Other outcomes:
Locations:
city: Munich
country: Germany
city: Budapest
country: Hungary
city: Warsaw
country: Poland
city: Cape Town
country: South Africa
city: London
country: United Kingdom
Study officials:
affiliation: City of London Migraine Clinic
name: Anne MacGregor, DIPM MFFP
role: PRINCIPAL_INVESTIGATOR
References:
citation: MacGregor EA, Brandes JL, Silberstein S, Jeka S, Czapinski P, Shaw B, Pawsey S. Safety and tolerability of short-term preventive frovatriptan: a combined analysis. Headache. 2009 Oct;49(9):1298-314. doi: 10.1111/j.1526-4610.2009.01513.x.