Clinical trial NCT03040479: Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic Function
Official title: A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Algorithme Pharma Inc
name: CoLucid Pharmaceuticals
First posted: 2017-02-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

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
* Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF)

Participants with Normal Hepatic Function:

* Clinical laboratory values within the laboratory's stated normal range; if not within this range, these must be without any clinical significance
* Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, endocrinology, electrocardiogram \[ECG\], and urinalysis)
* Must match by gender, as well as to the pooled mean values for age (± 10 years) and weight (± 20%) of participants with hepatic impairment

Hepatic Impaired Participants:

* Considered clinically stable in the opinion of the Investigator
* Presence of mild hepatic impairment (Child-Pugh Class A: 5-6 points) or moderate hepatic impairment (Child-Pugh Class B: 7-9 points) at screening

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
* Participants who took an Investigational Product (in another clinical trial) in the previous 28 days before day 1 of this study
* Participants who have already participated in this clinical study
* Donation of 500 milliliters (mL) or more of blood in the previous 56 days before day 1 of this study

Participants with Normal Hepatic Function:

* Seated pulse rate less than or equal 50 Beats per Minute (bpm) or more than 100 bpm at screening
* Seated blood pressure below 90/60 millimeters of mercury (mmHg) or higher than 140/90 mmHg at screening
* Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects
* History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
* Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
* Presence of out-of-range cardiac interval (PR \< 110 milliseconds \[msec\], PR \> 220 msec, QRS \< 60 msec, QRS \>119 msec and QTc \> 450 msec for males and \> 460 msec for females) on the screening ECG or other clinically significant ECG abnormalities
* Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
* Positive screening of alcohol and/or drugs of abuse
* Positive results to Hepatitis B surface Antigen (HBsAG \[B\] \[hepatitis B\]) or Hepatitis C Virus (HCV \[C\]) tests
* Any clinically significant illness in the previous 28 days before day 1 of this study
* Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
* Participants who donated 50 mL or more of blood in the previous 28 days before day 1 of this study

Hepatic Impaired Participants:

* Seated pulse rate less than 40 bpm or more than 110 bpm at screening
* Seated blood pressure below 90/50 mmHg or higher than 170/100 mmHg at screening
* History of hepatic transplant
* Acute exacerbation of hepatic disease within 14 days of study drug administration
* History or presence, in the opinion of the Investigator, of significant clinically unstable respiratory, cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
* Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c \>10%
* Evidence of hepatocellular carcinoma present or acute hepatic disease from infection or drug toxicity at the time of screening
* Presence of severe encephalopathy
* Presence of surgically-created or transjugular intrahepatic portal systemic shunts
* History of any major surgery within 6 months before Day 1
* History of bariatric surgery or any other gastrointestinal surgery that may induce malabsorption
* Estimated creatinine clearance by Cockcroft-Gault equation \< 40 mL/min/1.73 m² at screening
* Presence of clinically significant physical, laboratory, or ECG finding that, in the opinion of the Investigator and/or Sponsor, may interfere with any aspect of study conduct or interpretation of results
* Participants with acute, unstable, or untreated significant medical conditions.
* Positive screening of alcohol and/or drugs of abuse unless results can be explained by a prescription medication
* Participants who donated 100 mL or more of blood in the previous 28 days before day 1 of this study

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
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
measure: Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
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
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])
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
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])
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
measure: Pharmacokinetics: Apparent Elimination Rate Constant (λZ)
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
measure: Pharmacokinetics: Terminal Elimination Half-life (T1/2)
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
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up To 35 days
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Knoxville
country: United States
facility: NOCCR
state: Kentucky
city: Mount-Royal
country: Canada
facility: Altasciences Company Inc./Algorithme Pharma
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: