A Placebo-Controlled Group Sequential Adaptive Treatment Assignment Study of Intravenous COL-144 (LY573144) in the Acute Treatment of Migraine

INTERVENTION: Product Name: COL‐144 (LY573144; Eli Lilly & Company) Product Code: COL‐144 Pharmaceutical Form: Intravenous infusion Current Sponsor code: COL‐144 Other descriptive name: Benzamide, 2,4,6‐trifluoro‐N‐[6‐[(1‐methyl‐4‐piperidinyl)carbonyl]‐2‐pyridinyl]‐, butanedioate (2:1) Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Intravenous infusion Route of administration of the placebo: Intravenous use CONDITION: Migraine ; MedDRA version: 8.1 Level: PT Classification code 10027599 Term: Migraine INCLUSION CRITERIA: 1. Patients with migraine with or without aura fulfilling the IHS diagnostic criteria 1.1 and 1.2.1 (2004) 2. History of migraine of at least 1 year 3. Migraine onset before the age of 50 years 4. History of 1 – 8 migraine attacks per month 5. Male or female subjects aged 18 to 65 years 6. Female patients of child‐bearing potential must be using a highly effective form of contraception (eg combined oral contraceptive, IUD, abstinence, vasectomized partner) 7. Able and willing to return to the clinic for treatment within 4 hours of the onset of a migraine headache 8. Able and willing to give written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range PRIMARY OUTCOME: Main Objective: To evaluate the efficacy (headache response at two hours) of a range of intravenous doses of COL‐144 in order to select a dose range for further evaluation. Primary end point(s): The primary efficacy endpoint is headache response, defined as a reduction in headache severity from moderate or severe at baseline to mild or no headache, at two hours after initiation of infusion of study drug.; ; Secondary endpoints are: ; ‐ rates of headache response as defined above at 10min, 20min, 40min, 60min, ; 90min, 180min, and 240min after initiation of study drug; ‐ proportion of patients headache free at 10min, 20min, 40min, 60min, 90min, ; 120min, 180min, and 240min after initiation of study drug; ‐ rates of sustained response, defined as a moderate or severe headache at ; baseline which became mild or no headache by 2 hours after initiation of study ; drug and which did not recur (become moderate or severe) within 24 hours of ; initiation of study drug or use of rescue medication within 24 hours of initiation of ; study drug; ‐ rates of sustained pain free, defined as a moderate or severe headache at ; baseline which became no headache by 2 hours after initiation of study drug and ; which did not recur (become mild, moderate or severe) within 24 hours of initiation ; of study drug or use of rescue medication within 24 hours of initiation of study drug; ‐ relief of nausea, vomiting, photophobia, and phonophobia; ‐ degree of clinical disability; ‐ proportion of patients using rescue medication between 2 and 24 hours after study ; drug ; ‐ patient global impression (seven point scale); ; The primary safety endpoints of this study are:; ‐ Adverse events; ‐ 12‐Lead electrocardiogram (ECG); ‐ Vital signs; ‐ Clinical chemistry, hematology, and urinalysis; ‐ Physical examination Secondary Objective: To explore the time course and effect of a range of dose levels of COL‐144 on features of the migraine including; headache response, proportion of patients pain free, headache recurrence, nausea, photophobia, phonophobia, disability, use of rescue medication and patient global impression.