A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Hepatic Function
Overview
- Phase
- Phase 1
- Intervention
- lasmiditan 200 mg
- Conditions
- Migraine
- Sponsor
- Eli Lilly and Company
- Enrollment
- 24
- Locations
- 3
- Primary Endpoint
- Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a multicenter, open-label, non-randomized, parallel-group, single dose study. This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function.
Detailed Description
This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function. Approximately four participants with mild hepatic impairment will be enrolled first (Group 1). To ensure participant safety, following dosing of these first four participants, a safety meeting will take place to review the safety data prior to dosing additional participants. After safety and pharmacokinetic (PK) results from the first four participants have been reviewed, an additional four participants with mild hepatic impairment (remainder of Group 1) will be enrolled concurrently with the moderate hepatic impairment group (Group 2). Thereafter, matched participants with normal hepatic function (Group 3) will be enrolled. All participants will participate in one treatment period and will receive a single dose of lasmiditan in the fasting state.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All participants:
- •Availability for the entire study period
- •Motivated participant and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
- •Male or female participants
- •A female participant of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the drug administration, during the study and for at least 60 days after the dose.
- •A male participant with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must be unable to procreate, or agrees to use an accepted contraceptive regimens from first drug administration until 3 months after the drug administration.
- •A male participant agrees to refrain from sperm donation from drug administration until 90 days after the drug administration
- •Participant aged of at least 18 years
- •Participant with a body mass index (BMI) greater than or equal to (≥1) 8.5 kilogram per square meter (kg/m²)
- •Light-, non- or ex-smokers
Exclusion Criteria
- •All Participants:
- •Females who are pregnant or are lactating
- •History of significant hypersensitivity to lasmiditan or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- •Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
- •Participant is at imminent risk of suicide (positive response to question 4 or 5 on the Columbia- Suicide Severity Rating Scale \[C-SSRS\]) or had a suicide attempt within 6 months prior to screening
- •Presence or history of any disorder (including Parkinson disease) that could interfere with completion of the study based on the opinion of the Principal Investigator
- •Any history of tuberculosis and/or prophylaxis for tuberculosis
- •Positive results to human immunodeficiency virus antibody/antigen (HIV Ag/Ab) Combo tests (and HIV I \& II screen at Orlando Clinical Research Center site)
- •Females who are pregnant according to a positive pregnancy test
- •Participants who took lasmiditan in the previous 28 days before Day 1 of this study
Arms & Interventions
Mild hepatic impairment
lasmiditan 200 mg single dose
Intervention: lasmiditan 200 mg
Moderate hepatic impairment
lasmiditan 200 mg single dose
Intervention: lasmiditan 200 mg
Healthy participants
lasmiditan 200 mg single dose
Intervention: lasmiditan 200 mg
Outcomes
Primary Outcomes
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])
Time Frame: 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
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.
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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: Terminal Elimination Half-life (T1/2)
Time Frame: 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.
Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
Time Frame: 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
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])
Time Frame: 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
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.
Pharmacokinetics: Apparent Elimination Rate Constant (λZ)
Time Frame: 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.
Secondary Outcomes
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up To 35 days)