CoLucid Pharma Announces Achievement Of Secondary Endpoints In SAMURAI

• 100 mg and 200 mg doses of lasmiditan were more efficacious than placebo on headache pain relief at the two-hour time point (p < 0.001)
  
• 100 mg and 200 mg doses of lasmiditan were more efficacious than placebo as rescue medication on headache pain freedom at the two-hour time point (p < 0.001 and p < 0.012)
• 100 mg and 200 mg doses of lasmiditan were more effective than placebo in reducing migraine related disability at two-hour time point (p < 0.001) and improving Patient Global Impression of Change (p < 0.001)
• Second dose of lasmiditan was well tolerated and no significant difference in cardiovascular adverse events was observed in patients dosed with lasmiditan vs. placebo
• Detailed results from SAMURAI presented at a symposium during the 5th European Headache and Migraine Trust International Congress (EHMTIC 2016) in Glasgow, Scotland on September 17, 2016

CAMBRIDGE, Mass., Sept. 17, 2016 (GLOBE NEWSWIRE) -- CoLucid Pharmaceuticals, Inc., a biopharmaceutical company that is developing lasmiditan oral tablets for the acute treatment of migraine in adults, with or without aura, announced today that its Phase 3 pivotal trial evaluating lasmiditan, the SAMURAI study, had achieved secondary endpoints with statistical significance (p < 0.001 – p < 0.012). SAMURAI was a randomized, double-blind, placebo-controlled parallel group study designed to evaluate the efficacy and safety of lasmiditan (100 mg and 200 mg) in comparison to placebo. Lasmiditan doses of 100 mg and 200 mg were efficacious on headache pain freedom and the most bothersome symptom (MBS) freedom at the two-hour time point (p < 0.001), the primary and key secondary endpoints of the study. SAMURAI is the first of two Phase 3 pivotal trials of lasmiditan, each being conducted under a Special Protocol Assessment agreement (“SPA”) with the U.S. Food and Drug Administration (“FDA”).

Secondary Endpoints

Efficacy

Secondary efficacy endpoints of lasmiditan (100 mg and 200 mg) in SAMURAI included:

• the efficacy of lasmiditan in comparison to placebo based on migraine headache pain relief two hours after dosing in the intent to treat (ITT) population
• the efficacy of lasmiditan in comparison to placebo based on freedom from migraine headache pain two hours after dosing when used as a second dose for either rescue or recurrence in the ITT population
• the efficacy of lasmiditan in comparison to placebo based on the proportion of patients absent each associated symptom of migraine (nausea, phonophobia or photophobia) two hours after dosing in the ITT population
• the efficacy of lasmiditan in comparison to placebo based on Patient Global Impression of Change (PGIC) two hours after dosing in the ITT population
• the efficacy of lasmiditan in comparison to placebo based on disability related to migraine two hours after dosing in the ITT population

Data from the study were collected using electronic diaries during the treated attack. Beginning pre-dose, patients indicated their degree of headache pain on a 4-point scale: 0, no pain; 1, mild pain; 2, moderate pain; or 3, severe pain. Patients also indicated the presence or absence of nausea, phonophobia or photophobia, and at the pre-dose time point identified the associated symptom present that was “most bothersome.” At each time point assessment, patients were asked to indicate the degree of headache pain and the presence or absence of each associated symptom. At the two-hour endpoint, patients indicated their Patient Global Impression of Change (very much better, much better, a little better, no change, a little worse, much worse, very much worse). At the two-hour endpoint, patients also indicated their disability related to migraine on a 4-point scale:  0, not at all; 1, mild interference; 2, marked interference; 3, completely, needs bed rest.

Migraine headache relief was defined as moderate or severe headache pain at baseline reduced to mild or no headache pain at the time point assessment. Lasmiditan was effective in relieving migraine headache pain at two hours (p < 0.001) as compared to placebo.

Patients were randomized at 2:1 lasmiditan to placebo for a second dose, unless the initial dose was placebo. Patients were allowed to take a second dose of study drug after the two-hour time point, but before the 24-hour time point, for rescue or recurrence. Rescue was defined as a second dose taken for a migraine for which headache pain freedom was not achieved at the two-hour time point after initial dosing. Recurrence was defined as a second dose taken for a migraine for which headache pain freedom was achieved at the two-hour time point but reoccurred within 24 hours after initial dosing. The utilization rate of a second dose was expressed as the proportion of patients who took any second dose of study drug in a treatment group to the safety population of the same treatment group.

Patients dosed with lasmiditan were less likely to use a second dose of study drug. Lasmiditan was effective on migraine headache pain freedom at the two-hour time point assessment following a second dose as a rescue medication as compared to placebo. The number of patients who took a second dose of study drug for recurrence was small (53 out of 1,671) with no significant difference between five treatment groups.

The MBS endpoint was patient-centric and measured treatment effect of study drug on associated symptoms of nausea, phonophobia and photophobia. Freedom from MBS at the two-hour time point assessment was a key secondary endpoint of SAMURAI and conforms to the FDA’s Draft Guidance for Industry, Migraine: Developing Drugs for Acute Treatment, issued in October 2014. Patients treated with lasmiditan 100 mg or 200 mg were more likely to be MBS free at the two-hour time point assessment than patients treated with placebo (p < 0.001).

The distribution of baseline associated symptoms present in each dose group was relatively even.

However, patients were more likely to select photophobia as MBS if it were present at baseline than nausea or phonophobia.  This selection preference was expressed as a proportion of the number of patients who selected that baseline associated symptom as most bothersome versus the number of patients that had the baseline symptom.

The proportion of patients absent each associated symptom of migraine (nausea, phonophobia or photophobia) two hours after dosing was also measured as a secondary endpoint.