Migraine Disorders
Conditions
Brief summary
This is a prospective, randomized, open-label study in subjects with migraine who have completed the Phase 3 studies, COL MIG 301/LAHJ (NCT02439320) or COL MIG-302/LAHK (NCT02605174) or for a subset of lasmiditan-naïve subjects with migraine. The study is designed to evaluate the safety and tolerability of long-term intermittent use of lasmiditan 100 mg and of lasmiditan 200 mg, as the first dose and as a second dose, for the acute treatment of migraine. Long term efficacy will also be evaluated.
Interventions
DRUGLasmiditan
oral tablet
Sponsors
CoLucid Pharmaceuticals
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able and willing to give written informed consent and authorize Health Insurance Portability and Accountability Act (HIPAA). * Completed COL MIG-301 or COL MIG-302 within the last 12 weeks. Subjects that completed COL MIG-301 prior to COL MIG-305 being available will be allowed to enroll as long as enrollment occurs within 4 weeks of COL MIG-305 activation at their site. (NOTE: Additional subjects may qualify if they completed COL MIG-301 or COL MIG-302 \>12 weeks prior or if they have not participated in either prior study, but meet eligibility criteria outlined for COL MIG-302.) * Females of child-bearing potential must be using or willing to use a highly effective form of contraception (e.g. combined oral contraceptive, intrauterine device (IUD), abstinence or vasectomized partner). * Able and willing to complete an electronic diary to record details of all migraine attacks treated with study drug.
Exclusion criteria
* Any medical condition or clinical laboratory test which in the judgment of the Investigator makes the subject unsuitable for the study. * Pregnant or breast-feeding women. * Women of child-bearing potential not using or not willing to use highly effective contraception. * Participant is at imminent risk of suicide (positive response to question 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). * Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes since completing COL MIG-301/LAHJ (NCT02439320) or COL MIG-302/LAHK (NCT02605174). * Participation in any clinical trial of an experimental drug or device since completing EoS/Visit 2 of COL MIG 301/LAHJ (NCT02439320) or COL MIG-302/LAHK (NCT02605174).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 1 Treatment Emergent Adverse Event | Up to 12 months | An AE with an onset on or within 48 hours after a dose of study drug, or an event that worsened in intensity within 48 hours of a dose of study drug was considered a treatment-emergent adverse event (TEAE). A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Migraine Attacks With Pain Freedom (PF) at 2 Hours After Dose | Up to 12 months | Pain freedom is defined as a reduction in headache severity from mild (1), moderate (2), or severe (3) at baseline to none (0). |
| Percentage of Migraine Attacks With Most Bothersome Symptom-Free (MBS) at 2 Hours After Dose | Up to 12 months | MBS-free, defined as the absence of the associated symptom of migraine (nausea, phonophobia, and/or photophobia) at 2 hours postdose that was identified predose as the most bothersome symptom. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Medical Resource Utilization | Up to 12 months | Medical Resource utilization for any cardiovascular (CV) events and/or related resource utilization, such as visits to cardiologists, procedures, hospitalizations, new treatments or treatment adjustments for CV disease and any visits to an emergency room (ER) or physician's office for treatment of migraine was reported. |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lasmiditan 100mg Participants received oral dose of 100mg Lasmiditan with in four hours of onset of migraine attack. If the migraine did not respond within 2 hours after first dose or if responded and recurred then a second dose was permitted within 24 hours after first dose. | 1,046 |
| Lasmiditan 200mg Participants received oral dose of 200mg Lasmiditan with in four hours of onset of migraine attack. If the migraine did not respond with in 2 hours after first dose or if responded and recurred then a second dose was permitted within 24 hours after first dose. | 1,125 |
| Total | 2,171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 113 | 148 |
| Overall Study | Did Not Receive Study Drug | 55 | 86 |
| Overall Study | Lost to Follow-up | 102 | 93 |
| Overall Study | Missing | 1 | 0 |
| Overall Study | Non-Compliance | 57 | 55 |
| Overall Study | Physician Decision | 18 | 16 |
| Overall Study | Sponsor Request | 5 | 9 |
| Overall Study | Withdrawal by Subject | 229 | 214 |
Baseline characteristics
| Characteristic | Lasmiditan 100mg | Total | Lasmiditan 200mg |
|---|---|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 12.25 | 43.0 years STANDARD_DEVIATION 12.3 | 43.4 years STANDARD_DEVIATION 12.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 208 Participants | 448 Participants | 240 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 833 Participants | 1713 Participants | 880 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 203 Participants | 397 Participants | 194 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 25 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 22 Participants | 10 Participants |
| Race (NIH/OMB) White | 805 Participants | 1689 Participants | 884 Participants |
| Region of Enrollment Germany | 0 Participants | 22 Participants | 22 Participants |
| Region of Enrollment United Kingdom | 5 Participants | 43 Participants | 38 Participants |
| Region of Enrollment United States | 1041 Participants | 2106 Participants | 1065 Participants |
| Sex: Female, Male Female | 882 Participants | 1839 Participants | 957 Participants |
| Sex: Female, Male Male | 164 Participants | 330 Participants | 166 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 991 | 0 / 1,039 |
| other Total, other adverse events | 446 / 991 | 543 / 1,039 |
| serious Total, serious adverse events | 29 / 991 | 36 / 1,039 |
Outcome results
Primary
Number of Participants With at Least 1 Treatment Emergent Adverse Event
An AE with an onset on or within 48 hours after a dose of study drug, or an event that worsened in intensity within 48 hours of a dose of study drug was considered a treatment-emergent adverse event (TEAE). A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.
Time frame: Up to 12 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 100mg | Number of Participants With at Least 1 Treatment Emergent Adverse Event | 447 Participants |
| Lasmiditan 200mg | Number of Participants With at Least 1 Treatment Emergent Adverse Event | 545 Participants |
Secondary
Percentage of Migraine Attacks With Most Bothersome Symptom-Free (MBS) at 2 Hours After Dose
MBS-free, defined as the absence of the associated symptom of migraine (nausea, phonophobia, and/or photophobia) at 2 hours postdose that was identified predose as the most bothersome symptom.
Time frame: Up to 12 months
Population: All randomized participants who treated at least 1 qualifying migraine attack within 4 hours of onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 100mg | Percentage of Migraine Attacks With Most Bothersome Symptom-Free (MBS) at 2 Hours After Dose | 37.2 Percentage of MBS-Free Migraine Attacks |
| Lasmiditan 200mg | Percentage of Migraine Attacks With Most Bothersome Symptom-Free (MBS) at 2 Hours After Dose | 40.8 Percentage of MBS-Free Migraine Attacks |
Secondary
Percentage of Migraine Attacks With Pain Freedom (PF) at 2 Hours After Dose
Pain freedom is defined as a reduction in headache severity from mild (1), moderate (2), or severe (3) at baseline to none (0).
Time frame: Up to 12 months
Population: All randomized participants who treated at least 1 qualifying migraine attack within 4 hours of onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 100mg | Percentage of Migraine Attacks With Pain Freedom (PF) at 2 Hours After Dose | 26.7 Percentage of PF Migraine Attacks |
| Lasmiditan 200mg | Percentage of Migraine Attacks With Pain Freedom (PF) at 2 Hours After Dose | 32.2 Percentage of PF Migraine Attacks |
Other Pre-specified
Percentage of Participants With Medical Resource Utilization
Medical Resource utilization for any cardiovascular (CV) events and/or related resource utilization, such as visits to cardiologists, procedures, hospitalizations, new treatments or treatment adjustments for CV disease and any visits to an emergency room (ER) or physician's office for treatment of migraine was reported.
Time frame: Up to 12 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | Hospitalized | 0.5 Percentage of Participants |
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | Visit to primary care | 0.8 Percentage of Participants |
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | Procedures performed | 0.8 Percentage of Participants |
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | Visit to Other providers | 0.1 Percentage of Participants |
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | ER visits or visits to Physicians Office | 2.6 Percentage of Participants |
| Lasmiditan 100mg | Percentage of Participants With Medical Resource Utilization | Visit to cardiologist | 0.6 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | ER visits or visits to Physicians Office | 2.6 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | Visit to cardiologist | 0.6 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | Visit to Other providers | 0.2 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | Hospitalized | 0.2 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | Procedures performed | 0.6 Percentage of Participants |
| Lasmiditan 200mg | Percentage of Participants With Medical Resource Utilization | Visit to primary care | 0.9 Percentage of Participants |