- 1,155 patients have been randomized in GLADIATOR, with a retention rate of 74% of those patients
- 100 mg and 200 mg doses of lasmiditan collectively have been administered over 7,500 times in GLADIATOR and have been well tolerated with no significant increase in cardiovascular adverse events in patients
- Interim update on GLADIATOR 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. 19, 2016 (GLOBE NEWSWIRE) -- CoLucid Pharmaceuticals, Inc.(Nasdaq: CLCD ), a biopharmaceutical company that is developing lasmiditan oral tablets for the acute treatment of migraine in adults, with or without aura, provided an interim update on its Phase 3 long-term, open-label trial evaluating lasmiditan, the GLADIATOR study. Migraine patients who have completed CoLucid’s first Phase 3 pivotal trial, SAMURAI, as well as CoLucid’s second Phase 3 pivotal trial, SPARTAN, are eligible to enroll in GLADIATOR. GLADIATOR is expected to enroll up to a total of 2,580 patients, who will be randomized to receive 100 mg or 200 mg of lasmiditan, and treat up to eight migraine attacks per month for one year.
The primary endpoint of the GLADIATOR study is the proportion of patients and the proportion of attacks associated with any adverse event and with specific adverse events. The secondary endpoint is the proportion of migraine attacks treated with lasmiditan 100 mg and with lasmiditan 200 mg which at the two-hour time point, calculated for each three-month period within a 12-month period.
An interim update from GLADIATOR was presented by Dr. Uwe Reuter, Department of Neurology and Director of the Headache Center, Charité Universitätsmedizin Berlin, at a symposium during the 5th European Headache and Migraine Trust International Congress (EHMTIC 2016) that took place in Glasgow, Scotland on September 17, 2016. A copy of the presentation that was utilized at the symposium is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/201...tation.pdf .
Enrollment and Retention
GLADIATOR has randomized 1,155 patients to date, or approximately 45% of the anticipated 2,580 patients to be randomized. Of patients randomized to date, the following table provides a summary by each dose group and in total of the number of randomized patients, the number of patients who remain active in the study, the number of patients who have discontinued and the retention rate. Overall, the retention rate in GLADIATOR to date has been 74%.
| Enrollment | Lasmiditan 100mg | Lasmiditan 200mg | Total | ||||||
| Randomized total | 558 | 597 | 1,155 | ||||||
| Active | 395 | 456 | 851 | ||||||
| Discontinued | 163 | 141 | 304 | ||||||
| Retention Rate | 71 | % | 76 | % | 74 | % | |||
Discontinuation from GLADIATOR was primarily driven by either adverse events or by patient request. Patient request usually indicated an unwillingness to participate in a 12-month study requiring daily electronic diary engagement. Discontinuation was fairly balanced between dose groups. The following table sets forth, by dose group and in total, the number and percentage of patients who have discontinued for which data is currently available regarding the reason for discontinuation.
| Lasmiditan 100 mg | Lasmiditan 200 mg | Total | |
| Discontinuations | 163 | 141 | 304 |
| Data to date (213 of 304 discontinuations), n (%) | 113 (53%) | 100 (47%) | 213 (100%) |
| Adverse Events | 40 (19%) | 43 (20%) | 83 (39%) |
| Patient request | 54 (25%) | 29 (14%) | 83 (39%) |
| Lost to follow-up | 8 (4%) | 8 (4%) | 16 (8%) |
| Non-compliance with protocol | 7 (3%) | 8 (4%) | 15 (7%) |
| Sponsor request | 2 (1%) | 5 (2%) | 7 (3%) |
| Investigator request | 2 (1%) | 4 (2%) | 6 (3%) |
| Pregnancy | 0 | 3 (1%) | 3 (1%) |
To date, 7,589 total doses of lasmiditan have been administered in GLADIATOR. First dose administration was relatively balanced between the 100 mg and 200 mg dose groups (2,849 and 2,614, respectively). Second dose utilization was 44% (1,257) for the 100 mg dose group and 33% (869) for the 200 mg dose group. The second dose utilization in GLADIATOR has been similar to that in SAMURAI, 44% vs. 46%, respectively, for the 100 mg dose group, and 33% vs. 39%, respectively, for the 200 mg dose group. The following table sets forth dosage data from GLADIATOR.
| Patients dosed in each arm (n=) | Lasmiditan 100 mg (n=473) | Lasmiditan 200 mg (n=465) | Total (n=938) | ||||||
| Count of first dose taken | 2,849 | 2,614 | 5,463 | ||||||
| Count of second dose taken | 1,257 | 869 | 2,126 | ||||||
| % of patients taking 2 nd dose | 44 | % | 33 | % | 39 | % | |||
| Total number of doses taken | 4,106 | 3,483 | 7,589 | ||||||
Adverse Events
Patients have been treated for multiple migraines with lasmiditan in GLADIATOR. Lasmiditan has been well tolerated in GLADIATOR, with the majority of treatment emergent adverse events (TEAE) being nervous system related. Importantly, there has not been a significant increase in cardiovascular adverse events in patients randomized in GLADIATOR. The following table sets forth the number of patients who experienced the specified TEAE within the safety population following a dose of study drug, followed by the total number of adverse events experienced by TEAE.
| TEAE, n (events) | Lasmiditan 100mg (n=558) | Lasmiditan 200mg (n=597) | All Patients (n=1,155) |
| Dizziness | 36 (48) | 40 (67) | 76 (115) |
| Paresthesia | 7 (15) | 1 (2) | 8 (17) |
| Somnolence | 2 (2) | 8 (12) | 10 (14) |
| Nausea | 15 (21) | 18 (39) | 33 (60) |
| Fatigue | 14 (16) | 10 (17) | 24 (33) |
| Lethargy | 4 (4) | 5 (7) | 9 (11) |
| Vertigo | 7 (11) | 11 (24) | 18 (35) |
“Interim GLADIATOR data demonstrate that lasmiditan is well tolerated and the retention rate looks very good for such a comprehensive long term study,” said Dr. Reuter. “The expansive use of e-diaries for real time data collection in GLADIATOR has been scientifically innovative for the migraine community.”
About Lasmiditan Lasmiditan has been designed for the acute treatment of migraine headaches in adults without the vasoconstrictor activity associated with previous generations of migraine therapies. It selectively targets 5-HT1F receptors expressed in the trigeminal pathway. Lasmiditan has been given the generic stem name “ditan,” which distinguishes it from other drug classes, including triptans, the current standard of care for migraine.
CoLucid has completed its first pivotal Phase 3 clinical trial of lasmiditan oral tablets, SAMURAI, which 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. Both 100 mg and 200 mg doses of lasmiditan were efficacious on headache pain freedom, the primary endpoint, and most bothersome symptom freedom, the key secondary endpoint, at the two-hour time point (p < 0.001). Both 100 mg and 200 mg doses of lasmiditan were also efficacious on headache pain relief at the two-hour time point (p < 0.001), efficacious as a rescue medication on headache pain freedom at the two-hour time point (p < 0.001 and p < 0.012), and effective in reducing migraine related disability at the two-hour time point (p < 0.001) and improving Patient Global Impression of Change (p < 0.001). Lasmiditan was well tolerated with no significant difference in cardiovascular adverse events in patients dosed with lasmiditan versus placebo. 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”).
CoLucid is currently enrolling patients in a second pivotal Phase 3 clinical trial of lasmiditan oral tablets, SPARTAN. The objective of SPARTAN is to evaluate the safety and efficacy of lasmiditan (50 mg, 100 mg and 200 mg) in comparison to placebo two hours after dosing on freedom from migraine headache pain, which is the primary endpoint, and on freedom from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia), which is the key secondary endpoint. SPARTAN is a randomized, double-blind, placebo-controlled parallel group study. The study is expected to treat a single migraine in up to 2,226 migraine patients with lasmiditan at approximately 140 sites in the United States, United Kingdom and Germany. CoLucid expects that migraine patients enrolled in SPARTAN will include those who also have one or more cardiovascular risk factors, stable cardiovascular disease or known coronary artery disease (“CAD”). CoLucid has obtained an SPA agreement from the FDA for SPARTAN. Top-line results from SPARTAN are expected in the second half of 2017.
CoLucid is also currently enrolling patients in GLADIATOR, a Phase 3 long-term, open-label trial of lasmiditan. GLADIATOR’s objective is to evaluate the safety and efficacy of lasmiditan, as well as resource utilization, functional outcomes and disability. Based on the results of GLADIATOR, CoLucid intends to build an appropriate safety database to support a New Drug Application (“NDA”) for lasmiditan. At the time of the NDA submission, it is anticipated that there will be more than 15,000 patient exposures to lasmiditan in the entire clinical program.
About Migraine Migraine is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation. An estimated 36 million Americans suffer from migraine. Migraine can be extremely disabling and costly, accounting for more than an estimated $20 billion in direct (e.g., doctor visits, medications) and indirect (e.g., missed work, lost productivity) expenses each year in the United States.
About CoLucid Pharmaceuticals, Inc. CoLucid was founded in 2005 and is developing lasmiditan oral tablets for the acute treatment of migraine headaches in adults and intravenous lasmiditan for the acute treatment of headache pain associated with migraine in adults in emergency room and other urgent care settings.
Forward-Looking Statements
Certain of the statements made in this press release are forward looking, such as those, among others, relating to CoLucid’s expectations for lasmiditan’s efficacy, anticipated marked demand, anticipated physician prescribing patterns, clinical trial enrollment goals and the timing of future clinical trials. Actual enrollment results, market demand, use of cash and other developments may occur that differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that enrollment goals will not be met, trials may not be commenced or successful or may take longer to complete than anticipated, regulatory approval may not be obtained, physicians may not prescribe lasmiditan, and projected cash needs and expected financial results may be different. More information about the risks and uncertainties faced by CoLucid are contained in its periodic reports filed with the Securities and Exchange Commission. CoLucid disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
CONTACT Thomas Mathers Chief Executive Officer CoLucid Pharmaceuticals, Inc. (857) 285-6494 Hans Vitzthum Managing Director LifeSci Advisors, LLC. (212) 915-2568
