Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of a range of oral doses of COL-144 in treating migraine headache, in order to select a dose or doses for further evaluation.

Detailed Description
-----------------
Migraine is a common chronic neurological disorder characterized by recurrent disabling episodes of moderate to severe headache accompanied by nausea, vomiting, photophobia, and phonophobia. Acute pharmacologic therapy for migraine aims to terminate the attack or reduce its severity. Analgesics are commonly used or, if these are ineffective, triptans. Since triptans are contraindicated in patients with coronary artery disease, uncontrolled hypertension, and cerebrovascular disease alternative medications are required for patients where simple analgesics do not work. COL-144 has no vasoconstrictor activity at clinically relevant concentrations and might meet this need. COL-144 was effective when given intravenously in a placebo-controlled dose-ranging study. This study investigates which dose of oral COL-144 is effective in the in acute treatment of migraine headache.

Official Title
-----------------
A Double Blind Randomized Placebo-Controlled Parallel Group Dose-Ranging Study of Oral COL-144 in the Acute Treatment of Migraine

Conditions
-----------------
Migraine Disorders

Intervention / Treatment
-----------------
* Drug: Lasmiditan
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 patients aged 18 to 65 years Female patients of child-bearing potential must be using a highly effective form of contraception (e.g., combined oral contraceptive, IUD, abstinence, vasectomized partner) Able and willing to give written informed consent Able and willing to complete a migraine diary card to record details of the attack treated with study medication Exclusion Criteria: History of life threatening or intolerable adverse reaction to any triptan Use of prescription migraine prophylactic drugs within 15 days (30 days for flunarizine) prior to Screening Visit and during study participation Using herbal preparations (e.g., feverfew, butterbur) for migraine prophylaxis Using 5-HT reuptake inhibitors Using drugs known to inhibit CYP450 enzymes (see Appendix 2 for details) 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) History of orthostatic hypotension 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 or hepatic 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 Known Hepatitis B or C or HIV infection Patients who are employees of the sponsor 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 drug product Patients who were treated with study medication in the COL MIG-201 study (Patients screened but not treated under that protocol are not excluded)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg Lasmiditan<br>50 mg lasmiditan administered orally (PO) | Drug: Lasmiditan<br>* Oral application of one dose of either 50 mg lasmiditan,100 mg lasmiditan, 200 mg lasmiditan, 400 mg lasmiditan or placebo as the first treatment for a new migraine attack providing that any aura symptoms have resolved and the headache is either moderate or severe and has been so for less than 4 hours.<br>* Other names: LY573144;|
| Experimental: 100 mg Lasmiditan<br>100 mg lasmiditan administered orally (PO) | Drug: Lasmiditan<br>* Oral application of one dose of either 50 mg lasmiditan,100 mg lasmiditan, 200 mg lasmiditan, 400 mg lasmiditan or placebo as the first treatment for a new migraine attack providing that any aura symptoms have resolved and the headache is either moderate or severe and has been so for less than 4 hours.<br>* Other names: LY573144;|
| Experimental: 200 mg Lasmiditan<br>200 mg lasmiditan administered orally (PO) | Drug: Lasmiditan<br>* Oral application of one dose of either 50 mg lasmiditan,100 mg lasmiditan, 200 mg lasmiditan, 400 mg lasmiditan or placebo as the first treatment for a new migraine attack providing that any aura symptoms have resolved and the headache is either moderate or severe and has been so for less than 4 hours.<br>* Other names: LY573144;|
| Experimental: 400 mg Lasmiditan<br>400 mg lasmiditan administered orally (PO) | Drug: Lasmiditan<br>* Oral application of one dose of either 50 mg lasmiditan,100 mg lasmiditan, 200 mg lasmiditan, 400 mg lasmiditan or placebo as the first treatment for a new migraine attack providing that any aura symptoms have resolved and the headache is either moderate or severe and has been so for less than 4 hours.<br>* Other names: LY573144;|
| Placebo Comparator: Placebo<br>Placebo administered orally (PO) | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Headache Response | 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 administration of study drug. | 2 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | The percentage of participants defined as mild, moderate, or severe headache pain becoming none. | 2 hours post dose | 
| Percentage of Participants With Headache Recurrence | Participants who received study drug and which became pain free at 2 hours postdose and worsened again upto 24 hours post-dose. | up to 24 hours postdose | 
| Percentage of Participants With Headache Severity (4 Point Rating Scale) | Headache severity was evaluated by the participant using the International Headache Society (IHS) four point headache severity rating scale (0=no pain, 1=mild pain, 2=moderate pain, and 3=severe pain) with a lower score being less severe and a higher score being more severe. | 2 hours postdose | 
| Percentage of Participants Who Have Symptoms of Nausea | Percentage of participants who have symptoms of nausea two hours post treatment. | 2 hours postdose | 
| Percentage of Participants Who Have Symptoms Phonophobia | Percentage of participants who have symptoms of phonophobia two hours post treatment. | 2 hours postdose | 
| Percentage of Participants Who Have Photophobia | Percentage of participants who have symptoms of photophobia two hours post treatment. | 2 hours postdose | 
| Percentage of Participants With Vomiting | Percentage of participants with vomiting 2 hours post treatment. | 2 hours postdose | 
| Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | The participant is asked How much is the migraine interfering with normal activities? on a 4 point scale 0-Not at all, 1-Mild interference, 2-Marked interference ,3-Completely needs bed rest, with a lower score having lower interference and higher score worse interference. | 2 hours postdose | 
| Percentage of Participants Who Used Rescue Medication | Rescue medication was permitted after completion of the 2 hour assessment if migraine did not respond (participant was not pain free). | Postdose 2 through 24 hours | 
| Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | PGI-I requests participants to mark the box that best describes their cluster 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, a lower number indicates much better and a higher number indicates worse. | 2 hours postdose | 
| Actual Time to Headache Relief and Time to Pain Free | The participant answered Did your migraine pain go away completely (pain free) within 24 hours of dosing and record the time. Actual time to meaningful pain relief and actual time to pain free will be censored at 24 hours if meaningful pain relief or pain free is documented to be greater than 24 hours after dosing and Did you experience meaningful relief (headache relief) from your migraine within 24 hours after dosing?. | up to 24 hours postdose | 
| Change From Baseline in Heart Rate | Change from baseline in assessment of vital signs (heart rate). | Baseline through Day 14 | 
| Change From Baseline in Systolic Blood Pressure | Change from baseline in vital signs (systolic blood pressure). | Baseline through Day 14 | 
| Change From Baseline in Diastolic Blood Pressure | Change from baseline in vital signs (diastolic blood pressure). | Baseline through Day 14 | 
| Percentage of Participants With Change From Baseline in Physical Examination Parameters | Participants were evaluated for skin, head, ear, nose and throat, cardiovascular and musculoskeletal changes from a normal screening to an abnormal screening. Changes in the physical examination noted as non-serious AEs or SAEs, regardless of causality, are located in the Reported Adverse Events section. | Baseline through Day 14 | 
| Change From Baseline in Hematology Tests | Hematology tests, including a complete blood count (CBC) measured red blood cells, white blood cells, hemoglobin, neutrophils and platelets. | Baseline through Day 14 | 
| Number of Serious Adverse Events | A summary of non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | up to 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COL-144, acute treatment, migraine