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lasmiditan

Phase 3

Migraine | Small molecule | Neurology |Eli Lilly and Company|Last Updated: Jul 29, 2022

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials8
Total Enrollment2,799
FDA Designations
No designations recorded
Clinical Trials (8)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03670810A Study of Lasmiditan (LY573144) Over Four Migraine AttacksPHASE3 COMPLETED 1,633Jun 24, 2019Jul 8, 2021Jul 29, 2022141 United States, Austria +15
NCT03962738A Study Lasmiditan (LY573144) in a Single Migraine Attack in Japanese Participants With MigrainePHASE2 COMPLETED 846May 31, 2019Jun 8, 2020Jun 11, 202134 Japan
NCT00384774A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of MigrainePHASE2 COMPLETED 130Nov 1, 2006Jun 1, 2007Dec 2, 20193 Finland, Germany +1
NCT03988088A Study of Lasmiditan (LY573144) in Children Aged 6 to 17 With MigrainePHASE1 COMPLETED 18Jul 22, 2019Feb 24, 2020Sep 1, 202011 United States, Japan +1
NCT03009162Study of Oral Lasmiditan in Participants With Normal and Impaired Renal FunctionPHASE1 COMPLETED 16Apr 1, 2017Jun 2, 2017Dec 2, 20192 Canada
NCT03076970Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy ParticipantsPHASE1 COMPLETED 42Mar 21, 2017Apr 13, 2017Dec 2, 20191 United States
NCT03040479Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic FunctionPHASE1 COMPLETED 24Mar 14, 2017Jul 17, 2017Nov 27, 20193 United States, Canada
NCT03012334The Effects of Lasmiditan on Simulated Driving Performance - Healthy ParticipantsPHASE1 COMPLETED 90Jan 16, 2017Jun 8, 2017Jan 10, 20201 Canada
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Study Endpoints
Primary Endpoints
Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack
2 Hours Postdose

Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack.

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks
2 Hours Postdose

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.

Percentage of Participants Who Are Headache Pain Free In High Dose Group (200 mg Lasmiditan)
2 Hours Postdose

Percentage of participants who were headache pain free (defined as moderate or severe pain becoming none) at 2 hours postdose.

Number of Participants With Headache Response at Two Hours After Initiation of Infusion of Study Drug
2 hours post dose

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
0.5, 1, 1.5, 2, 3, 4, 8, 12 and 24 hours postdose

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
0.5, 1, 1.5, 2, 3, 4, 8, 12 and 24 hours postdose

PK: Area Under the Concentration-Versus-Time Curve (AUC) from Time Zero to Infinity (AUC\[0-∞\]) of Lasmiditan.

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours, postdose

Maximum observed plasma concentration of lasmiditan.

Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours, postdose

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

Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])
Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours, postdose

Area Under the Concentration Versus Time Curve (AUC) from time zero to tlast (AUC\[0- tlast\]) of lasmiditan.

Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])
Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours, postdose

Area Under the Concentration Versus Time Curve (AUC) from time zero to infinity (AUC\[0-inf\]) of lasmiditan.

Pharmacokinetics: Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae [0-t])
Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

Amount excreted in urine (calculated as total lasmiditan concentration multiplied by volume of urine)

Pharmacokinetics: Fraction of Dose Excreted in Urine (fe)
Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

Fraction of dose excreted in urine (Ae / dose)

Pharmacokinetics: Renal Clearance (CLr)
Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

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)

Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration
Pre-dose, 24 hours post-dose

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.

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration
Pre-dose, 24 hours post-dose

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.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Up to 6 weeks

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.

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

Maximum observed plasma concentration.

Pharmacokinetics: Apparent Elimination Rate Constant (λZ)
Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve.

Pharmacokinetics: Terminal Elimination Half-life (T1/2)
Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

Terminal elimination half-life, calculated as ln(2)/λZ.

Simulated Driving Performance in Healthy Participants as Measured by Standard Deviation of Lateral Position (SDLP) Using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim)
Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

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.

Secondary Endpoints
Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack
2 Hours Postdose
Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks
2 Hours Postdose
Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack
24 Hours
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
100 milligram (mg) LasmiditanEXPERIMENTALParticipants 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 LasmiditanEXPERIMENTALParticipants 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 SequencePLACEBO_COMPARATORControl 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 SequencePLACEBO_COMPARATORControl 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)EXPERIMENTALParticipants 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 MEEEXPERIMENTALParticipants 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 MEEPLACEBO_COMPARATORControl 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 MEEPLACEBO_COMPARATORControl 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 ExtensionEXPERIMENTALParticipants initially received 100 mg Lasmiditan at the first OLE visit, with flexible dosing (50, 100, or 200 mg) thereafter to optimize efficacy and tolerability.
50 milligram (mg) LasmiditanEXPERIMENTAL50 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack.
100 mg LasmiditanEXPERIMENTAL100 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack.
PlaceboPLACEBO_COMPARATORPlacebo tablets (to match 50 mg, 100 mg, 200 mg Lasmiditan dose tablets) administered once orally to treat a single migraine attack.
LasmiditanEXPERIMENTALParticipants received escalating doses of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 45 mg of lasmiditan as intravenous injection.
Renal impaired participantsEXPERIMENTALParticipants received single 200 milligrams (mg) oral tablet of lasmiditan.
Healthy participantsEXPERIMENTALParticipants received single 200 mg oral tablet of lasmiditan.
Lasmiditan 200 mgEXPERIMENTALsingle oral tablet
Sumatriptan 100 mgACTIVE_COMPARATORsingle oral tablet
Combination of lasmiditan and sumatriptanEXPERIMENTALsingle oral tablet of each
Mild hepatic impairmentEXPERIMENTALlasmiditan 200 mg single dose
Moderate hepatic impairmentEXPERIMENTALlasmiditan 200 mg single dose
Lasmiditan 50mg (milligrams)EXPERIMENTALParticipants 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.
Lasmiditan 100mgEXPERIMENTALParticipants received 100mg 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.
Lasmiditan 200mgEXPERIMENTALParticipants received 200mg of Lasmiditan tablets given as single doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.
Alprazolam 1mgACTIVE_COMPARATORParticipants 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.
Interventions
NameTypeDescription
LasmiditanDRUGAdministered orally.
PlaceboDRUGAdministered orally.
lasmiditan 200 mgDRUGdrug including single placebo tablet
SumatriptanDRUGdrug including single placebo tablet
matching placeboDRUGsingle oral tablet -given with single lasmiditan tablet and with single sumatriptan tablet.
AlprazolamDRUGActive comparator based on treatment sequence in 5-way crossover
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites141

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...

Countries:United StatesAustriaBelgiumChinaCzechiaDenmarkFranceGermanyHungaryIndiaItalyMexicoNetherlandsRussiaSpainSwitzerlandUnited KingdomJapanFinlandPuerto RicoCanada
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