Trial Outcomes & Findings for Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration (NCT NCT03040362)

NCT ID: NCT03040362

Last Updated: 2020-01-10

Results Overview

Maximum observed concentration based on plasma concentrations of lasmiditan.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 8 participants
• Primary outcome timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose
• Results posted on: 2020-01-10

Participant Flow

Participants were preceded by an overnight fast (at least 10 hours) from food (not including water) before receiving a dose of [14C]-lasmiditan.

Participant milestones

Measure	[14C]-Lasmiditan Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Overall Study STARTED	8
Overall Study Received at Least 1dose of Study Drug	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration

Baseline characteristics by cohort

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Age, Continuous	39 years STANDARD_DEVIATION 15.2 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Maximum observed concentration based on plasma concentrations of lasmiditan.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)	299 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36

PRIMARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Time to maximum concentration based on plasma concentrations of lasmiditan.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)	2.02 hours (hr) Interval 2.0 to 3.0

PRIMARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Area under concentration time curve (AUC) from Hour 0 to the last measurable concentration based on plasma concentrations of lasmiditan.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])	2100 nanogram*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 38

PRIMARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

AUC time zero to infinity (0-∞) of total radioactivity in blood/AUC0-∞ of total radioactivity in plasma.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
AUC Time Zero to Infinity (AUC0-∞) Blood/Plasma Ratio	0.948 Ratio Geometric Coefficient of Variation 6

PRIMARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

AUC time zero to infinity (0-∞) of lasmiditan in plasma/AUC0-∞ of total radioactivity in plasma.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
AUC Time Zero to Infinity (AUC0-∞) Plasma Lasmiditan/Total Radioactivity Ratio	0.131 Ratio Geometric Coefficient of Variation 18

SECONDARY outcome

Timeframe: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Amount of Lasmiditan and its metabolites (M3, M7, M8, (S,R)-M18, and (S,S)-M18) excreted in urine (Aeu) over sampling interval.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine Lasmiditan	5.81 milligram (mg) Standard Deviation 1.12
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine M3	1.62 milligram (mg) Standard Deviation 0.506
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine M7	0.00224 milligram (mg) Standard Deviation 0.000902
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine M8	132 milligram (mg) Standard Deviation 10.8
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine (S,R)-M18	1.85 milligram (mg) Standard Deviation 0.534
Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine (S,S)-M18	0.445 milligram (mg) Standard Deviation 0.127

SECONDARY outcome

Timeframe: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Percentage of lasmiditan recovered in urine (%UR), relative to dose administered calculated as %UR = 100 (amount of lasmiditan excreted in urine over a sampling interval (Aeu)/dose).

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Percentage of Lasmiditan Recovered in Urine, Relative to Dose Administered	2.91 % of lasmiditan dose Standard Deviation 0.561

SECONDARY outcome

Timeframe: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose

Population: All enrolled participants who received at least one dose of the study drug and had evaluable \[14C\]-lasmiditan PK data.

Renal clearance is the volume of plasma completely cleared of lasmiditan by the kidneys per unit time and calculated as CLR = Aeu/AUC0-x (where Aeu = amount of lasmiditan excreted in urine over a sampling interval; x is the last interval collected; for lasmiditan only).

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Renal Clearance (CLR)	2.89 liter per hour (L/hr) Standard Deviation 1.12

SECONDARY outcome

Timeframe: Up to 49 days

Population: All enrolled participants who received at least one dose of the study drug and had at least 1 post-dose safety assessment.

Safety assessed from time of consent through end of study (up to 49 days). 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.

Outcome measures

Measure	[14C]-Lasmiditan n=8 Participants Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs)	5 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events (SAEs)	0 Participants

Adverse Events

[14C]-Lasmiditan

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	[14C]-Lasmiditan n=8 participants at risk Participants were administered a single oral dose of radiolabeled \[14C\]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution on Day 1.
Ear and labyrinth disorders External ear pain	12.5% 1/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Gastrointestinal disorders Hypoaesthesia oral	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
General disorders Fatigue	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
General disorders Feeling drunk	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Injury, poisoning and procedural complications Post procedural contusion	25.0% 2/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Injury, poisoning and procedural complications Procedural pain	25.0% 2/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Injury, poisoning and procedural complications Procedural site reaction	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 1/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Nervous system disorders Dizziness	25.0% 2/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Nervous system disorders Sensory disturbance	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Psychiatric disorders Euphoric mood	12.5% 1/8 • Number of events 1 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 2/8 • Number of events 2 • Up To 49 Days All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee Details of the study and its results shall not be publicized in any form without prior consent of the Sponsor. Such approval is necessary to prevent premature disclosure of trade secrets and other confidential information.
• Publication restrictions are in place

Restriction type: OTHER