A Phase I, Multicenter, Open-Label, Parallel-Group Adaptive Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Renal Function
Overview
- Phase
- Phase 1
- Intervention
- Lasmiditan
- Conditions
- Migraine
- Sponsor
- Eli Lilly and Company
- Enrollment
- 16
- Locations
- 2
- Primary Endpoint
- Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a multi-center, open-label, non-randomized, parallel-group, adaptive, single dose study.
This study will enroll up to 32 participants using an adaptive design that can include up to 3 groups of 8 participants with different degree of renal impairment and one group of 8 control participants with normal renal function.
Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria and none of the exclusion criteria will be entered in the study.
First, approximately 16 participants will be enrolled with severe renal impairment and matched participants with normal renal function. There will be 8 participants in each of the following groups based on renal function at screening:
- Group 1: Healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] ≥ 90 milliliters per minute per 1.73 meters squared [mL/min/1.73m²])
- Group 2: Severe renal impairment participants (eGFR < 30 mL/min/1.73m²) Based on safety and pharmacokinetic (PK) results from participants with severe renal impairment (Group 2), Group 3 (Moderate Renal Impairment) and Group 4 (Mild Renal Impairment) will be enrolled if substantial change in the exposure of lasmiditan is observed in participants with severe renal impairment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 participant
- •A female participant if of childbearing potential - must be willing to use 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 of child bearing potential must be willing to use accepted contraceptive regimens.
- •A male participant agrees to refrain from sperm donation from drug administration until 3 months after the drug administration
- •Participant aged of at least 18 years
- •Participant with a body mass index (BMI) ≥18.50 kilogram per meter squared (kg/m²) and \< 42.00 kg/m²
- •Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before Day 1 of this study. An ex smoker is defined as someone who completely stopped smoking for at least 6 months before Day 1 of this study
- •Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the participant
- •Participants with Normal Renal Function:
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 antigen/antibody (HIV Ag/Ab) Combo, Hepatitis B surface antigen (HBsAG (B) (hepatitis B) or Hepatitis C Virus (HCV \[C\]) tests
- •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)
- •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
Arms & Interventions
Renal impaired participants
Participants received single 200 milligrams (mg) oral tablet of lasmiditan.
Intervention: Lasmiditan
Healthy participants
Participants received single 200 mg oral tablet of lasmiditan.
Intervention: Lasmiditan
Outcomes
Primary Outcomes
Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
Time Frame: 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 Infinity (AUC[0-inf])
Time Frame: 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])
Time Frame: 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: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])
Time Frame: 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: Fraction of Dose Excreted in Urine (fe)
Time Frame: 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: Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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: Renal Clearance (CLr)
Time Frame: 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)
Secondary Outcomes
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up To 7 days)