Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication REYVOW ® is indicated for the acute treatment of migraine with or without aura in adults. REYVOW ® is a serotonin (5-HT) 1F receptor agonist indicated for the acute treatment of migraine with or without aura in adults. ( 1 ) Limitations of Use REYVOW is not indicated for the preventive treatment of migraine. ( 1 ) Limitations of Use REYVOW is not indicated for the preventive treatment of migraine. FDA label
Also known as [14C]-lasmiditan, LY573144
Lasmiditan · 14 trials · 6 indications
Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack.
To evaluate the 2 out of 3 primary consistency endpoint, the results of ITT evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT evaluable attacks, only the first 3 will be considered. Pain-free was defined as mild, moderate, or severe headache pain becoming none at the indicated assessment time.
The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
The percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing being absent.
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.
The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
Percentage of participants who were headache pain free (defined as moderate or severe pain becoming none) at 2 hours postdose.
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.
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.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan.
PK: Area Under the Concentration-Versus-Time Curve (AUC) from Time Zero to Infinity (AUC\[0-∞\]) of Lasmiditan.
The Emax of Bipolar Drug Liking VAS Scores were derived as the maximum at-the-moment Drug Liking VAS score where the time to Emax was the corresponding time point at which the maximum score occurred. The bipolar Drug Liking VAS is consistent with FDA Guidance (January 2017) such that placebo should produce a score between 40 and 60 representing neutral drug-liking (ie, neither like nor dislike); a score ranging from 0 to 100 and a score of 0 indicates strong disliking, and a score of 100 indicates strong liking. Least squares mean (LS mean) was calculated using a linear mixed-effects model, including period, sequence, and treatment as fixed effects, and subject as a random effect, was used to evaluate the hypothesis tests of primary interest (at-the-moment Drug Liking) at the Emax.
PK: Cmax of Lasmiditan in Each Period.
PK: AUC(0-∞) of Lasmiditan in Each Period.
Maximum observed plasma concentration of lasmiditan.
Time of maximum observed plasma concentration; if it occurs at more than one time point, Tmax is defined as the first time point with this value
Area Under the Concentration Versus Time Curve (AUC) from time zero to tlast (AUC\[0- tlast\]) of lasmiditan.
Area Under the Concentration Versus Time Curve (AUC) from time zero to infinity (AUC\[0-inf\]) of lasmiditan.
Amount excreted in urine (calculated as total lasmiditan concentration multiplied by volume of urine)
Fraction of dose excreted in urine (Ae / dose)
Renal Clearance is the volume of blood or plasma that is completely cleared of the drug by the kidneys per unit time. (Ae(0-t)/AUC0-T)
Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Safety assessed from time of consent through end of study. A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the adverse events module of this record.
Maximum observed plasma concentration.
Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve.
Terminal elimination half-life, calculated as ln(2)/λZ.
The standard deviation of lateral position (SDLP) is the primary parameter used as stable measure of driving performance with high test-retest reliability. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. SDLP, was analyzed using a mixed model with fixed effects for sequence, period, and treatment, and a random effect for participant within sequence. A variance component covariance structure and Kenward-Roger degrees of freedom was used.
| Arm | Type | Description |
|---|---|---|
| 100 milligram (mg) Lasmiditan | EXPERIMENTAL | Participants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| 200 mg Lasmiditan | EXPERIMENTAL | Participants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| Control 1 Sequence | PLACEBO_COMPARATOR | Control 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| Control 2 Sequence | PLACEBO_COMPARATOR | Control 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| 100 mg Lasmiditan Maximum Extended Enrollment (MEE) | EXPERIMENTAL | Participants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| 200 mg Lasmiditan MEE | EXPERIMENTAL | Participants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| Control 1 Sequence MEE | PLACEBO_COMPARATOR | Control 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| Control 2 Sequence MEE | PLACEBO_COMPARATOR | Control 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. |
| Open Label Extension | EXPERIMENTAL | Participants initially received 100 mg Lasmiditan at the first OLE visit, with flexible dosing (50, 100, or 200 mg) thereafter to optimize efficacy and tolerability. |
| Lasmiditan 50 milligram (mg) | EXPERIMENTAL | Oral tablet. Lasmiditan 50 mg plus placebo (to match a lasmiditan dose). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed between 2 and 24 hours. |
| Lasmiditan 100 mg | EXPERIMENTAL | Oral tablet. Lasmiditan 100 mg plus placebo (to match a lasmiditan dose). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed between 2 and 24 hours. |
| Lasmiditan 200 mg | EXPERIMENTAL | Oral tablet. Lasmiditan 200 mg plus placebo (to match a lasmiditan dose). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed between 2 and 24 hours. |
| Placebo | PLACEBO_COMPARATOR | Oral tablet. Placebo tablets match each of the lasmiditan doses (50 mg, 100 mg and 200 mg). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed between 2 and 24 hours. |
| Lasmiditan 100mg | EXPERIMENTAL | Participants received oral dose of 100 milligrams (mg) 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. |
| Lasmiditan 200mg | EXPERIMENTAL | 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. |
| 50 milligram (mg) Lasmiditan | EXPERIMENTAL | 50 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack. |
| 100 mg Lasmiditan | EXPERIMENTAL | 100 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack. |
| 50 mg Lasmiditan | EXPERIMENTAL | 50 mg lasmiditan administered orally (PO) |
| 400 mg Lasmiditan | EXPERIMENTAL | 400 mg lasmiditan administered orally (PO) |
| Lasmiditan | EXPERIMENTAL | Participants received escalating doses of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 45 mg of lasmiditan as intravenous injection. |
| Alprazolam 2 milligram (mg) | ACTIVE_COMPARATOR | 2 mg of alprazolam was administered orally in one of five treatment periods |
| Lasmiditan 400 mg | EXPERIMENTAL | 400 mg of lasmiditan was administered orally in one of five treatment periods |
| Lasmiditan (Period 1) | EXPERIMENTAL | 200 mg Lasmiditan tablet given once orally during migraine attack. |
| Lasmiditan (Period 2) | EXPERIMENTAL | 200 mg Lasmiditan tablet given once orally during inter-ictal period. |
| Renal impaired participants | EXPERIMENTAL | Participants received single 200 milligrams (mg) oral tablet of lasmiditan. |
| Healthy participants | EXPERIMENTAL | Participants received single 200 mg oral tablet of lasmiditan. |
| Sumatriptan 100 mg | ACTIVE_COMPARATOR | single oral tablet |
| Combination of lasmiditan and sumatriptan | EXPERIMENTAL | single oral tablet of each |
| Mild hepatic impairment | EXPERIMENTAL | lasmiditan 200 mg single dose |
| Moderate hepatic impairment | EXPERIMENTAL | lasmiditan 200 mg single dose |
| Lasmiditan 50mg (milligrams) | EXPERIMENTAL | Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| Alprazolam 1mg | ACTIVE_COMPARATOR | Participants received 1mg of Alprazolam tablets as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. |
| Name | Type | Description |
|---|---|---|
| Lasmiditan | DRUG | Administered orally. |
| Placebo | DRUG | Administered orally. |
| Lasmiditan 50 mg | DRUG | One tablet lasmiditan 50 mg plus one placebo tablet (matching one of the lasmiditan doses) |
| Lasmiditan 100 mg | DRUG | One tablet lasmiditan 100 mg plus one placebo tablet (matching one of the lasmiditan doses) |
| Lasmiditan 200 mg | DRUG | One tablet lasmiditan 200 mg plus one placebo tablet (matching one of the lasmiditan doses) |
| Placebo (matches lasmiditan doses) | DRUG | - |
| Alprazolam | DRUG | Administered orally |
| Sumatriptan | DRUG | drug including single placebo tablet |
| matching placebo | DRUG | single oral tablet -given with single lasmiditan tablet and with single sumatriptan tablet. |
Inclusion Criteria: * Migraine with or without aura fulfilling the International Headache Society (IHS) diagnostic criteria 1.1 and 1.2.1 * History of disabling migraine for at least 1 year * Migraine onset before the age of 50 years * History of 3 to 8 migraine attacks per month (\<15 headache day...
Lasmiditan is used for the acute treatment of migraine, including migraine with or without aura, in adults. It is a small molecule developed for migraine disorders and has also been studied in children aged 6 to 17 with migraine. It is not intended for migraine prevention.
Lasmiditan targets the serotonin 5-HT1F receptor, also known as HTR1F. It acts as an agonist at this receptor. This receptor is distinct from the 5-HT1B/1D receptors targeted by triptans, which is relevant to its mechanism of action in acute migraine treatment.
Lasmiditan is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Eli Lilly conducted the clinical development program for lasmiditan, including Phase 3 trials in migraine.
Lasmiditan is in Phase 3 development. It has completed 8 clinical trials with a total enrollment of 3,005 participants. The trials include Phase 1, Phase 2, and Phase 3 studies, all of which are completed. No active trials are currently listed.
Lasmiditan has been studied in completed trials including NCT03670810, a Phase 3 study over four migraine attacks with 1,633 participants; NCT03962738, a Phase 2 study in Japanese participants with migraine; NCT03988088, a Phase 1 study in children aged 6 to 17; and NCT03286218, a Phase 1 abuse potential study.