Trial Outcomes & Findings for Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic Function (NCT NCT03040479)
NCT ID: NCT03040479
Last Updated: 2019-11-27
Results Overview
Maximum observed plasma concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
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
Results posted on
2019-11-27
Participant Flow
Male and female adult participants with normal hepatic function, mild and moderate hepatic impairment participated in the study. All participants participated in one treatment period and received a single dose of lasmiditan in the fasting state.Participants confined to the clinic 10 hours prior to dosing until 36 hours after drug administration.
Participant milestones
| Measure |
Mild Hepatic Impairment
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Healthy Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic Function
Baseline characteristics by cohort
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.9 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
59.1 years
STANDARD_DEVIATION 7.3 • n=7 Participants
|
58.0 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
57.0 years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
Maximum observed plasma concentration.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
|
261 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 51
|
294 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 47
|
220 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
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.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
|
2.00 hours (hr)
Interval 0.75 to 3.0
|
1.38 hours (hr)
Interval 0.75 to 2.0
|
2.52 hours (hr)
Interval 1.75 to 4.0
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
Cumulative area under the plasma concentration time curve calculated from 0 to TLQC using the linear trapezoidal method, where TLQC represents time of last observed quantifiable plasma concentration.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])
|
1750 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 38
|
2080 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 58
|
1590 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 31
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-tlast) + CLQC/λZ, where CLQC is the measured concentration at time TLQC Apparent elimination rate constant and λz is the estimated by linear regression of the terminal linear portion of the log concentration versus time curve.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])
|
1790 ng*h/mL
Geometric Coefficient of Variation 38
|
2170 ng*h/mL
Geometric Coefficient of Variation 59
|
1610 ng*h/mL
Geometric Coefficient of Variation 30
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics: Apparent Elimination Rate Constant (λZ)
|
0.121 1/hour (1/h)
Geometric Coefficient of Variation 31
|
0.089 1/hour (1/h)
Geometric Coefficient of Variation 14
|
0.136 1/hour (1/h)
Geometric Coefficient of Variation 9
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All enrolled participants who received at least one dose of the study drug and had evaluable lasmiditan PK data.
Terminal elimination half-life, calculated as ln(2)/λZ.
Outcome measures
| Measure |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Pharmacokinetics: Terminal Elimination Half-life (T1/2)
|
5.74 hours (hr)
Interval 3.57 to 7.95
|
7.82 hours (hr)
Interval 6.58 to 9.54
|
5.09 hours (hr)
Interval 4.56 to 5.72
|
SECONDARY outcome
Timeframe: Up To 35 daysPopulation: All enrolled participants who received at least one dose of the study drug.
Safety assessed from time of consent through end of study (up to 35 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 |
Mild Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
Healthy Participants
n=8 Participants
Participants received lasmiditan 200 mg single oral dose in the fasting state
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
3 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Participants
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mild Hepatic Impairment
n=8 participants at risk
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Moderate Hepatic Impairment
n=8 participants at risk
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
Healthy Participants
n=8 participants at risk
Participants received lasmiditan 200 mg single oral dose in the fasting state.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
1/8 • Number of events 1 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
0.00%
0/8 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
0.00%
0/8 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
12.5%
1/8 • Number of events 1 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
0.00%
0/8 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
0.00%
0/8 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/8 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
12.5%
1/8 • Number of events 1 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
25.0%
2/8 • Number of events 2 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Somnolence
|
37.5%
3/8 • Number of events 3 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
25.0%
2/8 • Number of events 2 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
25.0%
2/8 • Number of events 2 • Up To 35 days
All enrolled participants who received at least one dose of the study drug.
|
Additional Information
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