Study of Oral Lasmiditan in Participants With Normal and Impaired Renal Function

NCT03009162 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 16895CUD-P4-001COl MIG-113H8H-CD-LAHN
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)

  Maximum observed plasma concentration of lasmiditan.

  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

• Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)

  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

  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

• Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])

  Area Under the Concentration Versus Time Curve (AUC) from time zero to tlast (AUC\[0- tlast\]) of lasmiditan.

  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

• Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])

  Area Under the Concentration Versus Time Curve (AUC) from time zero to infinity (AUC\[0-inf\]) of lasmiditan.

  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

• Pharmacokinetics: Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae [0-t])

  Amount excreted in urine (calculated as total lasmiditan concentration multiplied by volume of urine)

  Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

• Pharmacokinetics: Fraction of Dose Excreted in Urine (fe)

  Fraction of dose excreted in urine (Ae / dose)

  Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

• Pharmacokinetics: Renal Clearance (CLr)

  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)

  Predose and intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 36 hours, postdose

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up To 7 days

Study Arms (2)

Renal impaired participants

EXPERIMENTAL

Participants received single 200 milligrams (mg) oral tablet of lasmiditan.

Drug: Lasmiditan

Healthy participants

EXPERIMENTAL

Participants received single 200 mg oral tablet of lasmiditan.

Drug: Lasmiditan

Interventions

Lasmiditan DRUG

200 mg, single oral tablet

Also known as: LY573144

Healthy participants; Renal impaired participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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, electrocardiogram \[ECG\], and urinalysis)
• For each gender, have to match by age (± 10 years) and weight (± 20%) to the pooled mean values of participants with severe renal impairment
• Have an eGFR ≥ 90 mL/min/1.73m² calculated using Modification of Diet in Renal Disease (MDRD) equation at screening
• Renal Impaired Participants:

You may not qualify if:

• 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
• 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
• Participants who donated 50 mL or more of blood in the previous 28 days before Day 1 of this study

Sponsors & Collaborators

• Eli Lilly and Company: lead
• CoLucid Pharmaceuticals: collaborator

Study Sites (2)

CIUSSS de l'est-de-l'île-de-Montréal - installation Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H3P3P1, Canada

Location

Algorithme Pharma

Mount Royal, Quebec, H3P3P1, Canada

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

lasmiditan

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 4, 2017
• Study Start: April 1, 2017
• Primary Completion: June 2, 2017
• Study Completion: June 2, 2017
• Last Updated: December 2, 2019
• Results First Posted: December 2, 2019

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)