E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Migraine headache with and without aura |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058734 |
E.1.2 | Term | Migraine prophylaxis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A multicenter, randomized, double blind, placebo-controlled, 3 group, parallel group design with moderate to severe migraine patients to assess the ability of daily administration of AST-726 at one of 2 doses to prophylactically reduce the number of migraine days in a 4 week period more than in subjects treated with placebo. |
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E.2.2 | Secondary objectives of the trial |
Number of subjects that respond with at least a 50% decrease in migraine days in each given 4 week Treatment Period will serve as a secondary endpoint. Additionally, the number of migraine headache attacks will serve as a secondary endpoint. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female between 18 and 75 years of age. 2.No medical conditions that would prohibit compliance with study procedures or conditions based on prestudy medical history, physical examination and routine laboratory tests as determined by the investigator. Subjects must have normally function kidneys as determined by the laboratory tests. (Excessive cobalamins are excreted primarily in the urine.) 3.Has migraine headaches with or without aura according to IHS guidelines (Committee, 2004). 4.Has had migraines for at least 6 months prior to study enrollment period. 5.Migraines began before age 50. 6.Has 2-10 attacks per month and greater than or equal to 3 migraine days per month in the last 3 mo prior to study enrollment. (The subject must be able to indicate they have been under a physicians care or referral for migraines for at least 3 months. 7.Has 2-10 attacks in 30 days during the Baseline Period. |
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E.4 | Principal exclusion criteria |
1.Used other intranasal medications within 4 weeks prior to study enrollment. 2.Is pregnant or breast-feeding (nursing) mother. All females of childbearing potential must have a negative blood pregnancy test at screening. Over the course of the study, females must practice a method of contraception with greater then 90% reliability, be sterile or postmenopausal. 3.Has known allergies to vitamin B12 or intranasal sprays. 4.Has headache equal to or greater than 18 days per month. 5.Has used migraine medications (e.g., topiramate, beta-blockers) for prophylactic use within 60 days prior to study enrollment. 6.Has excessive use of acute migraine medications (e.g., triptans, dihydroergotamine (DHE)) greater than 15 days per month. 7.Has taken nitroglycerine-containing medications within 60 days prior to study enrollment. 8.Failed more than 3 clinical studies of effective migraine prevention medications due to uncontrolled migraines. 9.Has had allergic or anaphylactic reaction to food colorants. (Patient may be admitted if they know that their food allergy is not due to a color agent.) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome variable will be change during each treatment period in headache days per month relative to baseline. A “headache day” will be defined as any day in which a patient reports a migraine headache episode of at least 60 minutes. The number of headache days reported in the patient diary will be standardized against a theoretical 30 day period reflecting the Baseline Period (Visit #2 to Visit #3) and the first through third Treatment Periods (Visits #3 to #4, Visits #4 to #5 and Visits #5 to #6, respectively). The standardized number of headache days will be calculated as the number of headache days in a given period divided by the number of days diary data observed multiplied by 30 days. Change in number of headache days during each of the three treatment periods will be calculated by subtracting the number of headache days during the baseline period from the number of headache days in each given treatment period. The primary time point will be the third Treatment Period (data obtained between Visits #5 and #6). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |