A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine

Study Overview
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Brief Summary
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This study evaluates the efficacy of a range of intravenous doses of COL-144 in the treatment of migraine headache in order to select a dose range for further studies.

Detailed Description
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This study is set up: 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, 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 participants pain-free, headache recurrence, nausea, photophobia, phonophobia, disability, use of rescue medication, patient global impression and vomiting to explore the safety and tolerability of a range of doses of COL-144 in terms of adverse events, physical exam, vital signs, laboratory evaluations, and ECGs to determine key PK parameters for COL-144 and to explore the relationship between the PK of COL-144 and the time course and extent of clinical response

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

Conditions
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Migraine

Intervention / Treatment
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* Drug: Lasmiditan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with migraine with or without aura fulfilling the IHS diagnostic criteria 1.1 and 1.2.1 (2004) History of migraine of at least 1 year Migraine onset before the age of 50 years History of 1 - 8 migraine attacks per month Male or female subjects aged 18 to 65 years Female patients of child-bearing potential must be using a highly effective form of contraception (eg combined oral contraceptive, IUD, abstinence, vasectomized partner) Able and willing to return to the clinic for treatment within 4 hours of the onset of a migraine headache Able and willing to give written informed consent Exclusion Criteria: History of life threatening or intolerable adverse reaction to any triptan Use of prescription migraine prophylactic drugs Pregnant or breast-feeding women Women of child-bearing potential not using highly effective contraception History or evidence of coronary artery disease, ischemic or hemorrhagic stroke, epilepsy or any other condition placing the patient at increased risk of seizures History of hypertension (controlled or uncontrolled) Sitting BP >160mmHg systolic or >90mmHg diastolic on 2 repeated measurements at screening Current use of hemodynamically active cardiovascular drugs History within the previous 3 years or current evidence of abuse of any drug, prescription or illicit, or alcohol Significant renal impairment Previous participation in this clinical trial Participation in any clinical trial of an experimental drug or device in the previous 30 days Any medical condition or laboratory test which in the judgment of the investigator makes the patient unsuitable for the study Relatives of, or staff directly reporting to, the investigator Patients with known hypersensitivity to COL-144, other 5HT1F receptor agonists or to any excipient of COL-144

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lasmiditan<br>Participants received escalating doses of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 45 mg of lasmiditan as intravenous injection. | Drug: Lasmiditan<br>* Administered as intravenous infusion<br>* Other names: LY573144, COL-144;|
| Placebo Comparator: Placebo<br>Participants received intravenous infusion of placebo solution. | Drug: Placebo<br>* Administered as intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Headache Response at Two Hours After Initiation of Infusion of Study Drug | Headache response is a binary response variable derived from the headache intensities recorded in the participant diary. Headache response is 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. | 2 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Headache Response 10 to 240 Minutes (Min) Post Dose | Headache response is 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. | 10, 20, 40, 60 90, 120, 180 and 240 minutes post dose | 
| Percentage of Participants Headache Free | Headache free is defined as a reduction in headache severity from moderate or severe at baseline to no headache pain at 10 min, 20 min, 40 min, 60 min, 90 min, 120 min, 180 min, and 240 min after initiation of study drug. | 10, 20, 40, 60 90, 120, 180 and 240 minutes post dose | 
| Number of Participants With Sustained Headache Response | Sustained headache response at 2 hours is a binary response variable derived from the headache intensities recorded in the participant diary. Sustained headache response was defined as moderate or severe headache pain at baseline which became mild or absent (pain free) at 2 hours after initiation of study drug and which did not recur (became moderate or severe) within 24 hours of initiation of study drug. If rescue medication was taken within 24 hours, this was considered a headache recurrence, even if no headache was reported. | 2 to 24 hours post dose | 
| Number of Participants With Sustained Pain Free | Sustained pain free was defined as moderate or severe headache pain at baseline which became mild or absent (pain free) at 2 hours after initiation of study drug and which did not recur (became moderate or severe) within 24 hours of initiation of study drug. If rescue medication was taken within 24 hours, this was considered a headache recurrence, even if no headache was reported. | 2 to 24 hours post dose | 
| Number of Participants With Absence of Nausea, Vomiting, Photophobia and Phonophobia | Number of participants with absence of nausea, vomiting, photophobia and phonophobia. | 2 hours post dose | 
| Number of Participants With Clinical Disability | Clinical disability for each participant was assessed using the Clinical Disability Questionnaire (CDQ). Participants graded their disability on the following scale: 0, no disability, able to function normally; 1, performance of daily activities mildly impaired, can still do everything but with difficulty; 2, performance of daily activities moderately impaired, unable to do some things; 3, performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary. | 2 hours post dose | 
| Percentage of Participants Using Rescue Medication | Use of rescue medication up to 24 hours after initiation of study drug. | 24 hours post dose | 
| Percentage of Participants Reporting a Score on the Patient Global Impression (PGI) | PGI scale is a participant-rated instrument that measures participants own global impression of their illness severity. Participants were asked to mark the box that best describes their headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. | 2 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine