A Study of Lasmiditan in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Lasmiditan; Drug: Rosuvastatin; Drug: Dabigatran Etexilate

• Registration Number: NCT04749914
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of the study is to investigate the blood concentrations of dabigatran etexilate and rosuvastatin when taken alone compared to when taken together with lasmiditan in healthy participants. The safety and tolerability of dabigatran etexilate or rosuvastatin in combination with lasmiditan will also be evaluated in healthy participants. The study has two parts. Each part will last up to 17 days, not including screening.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-08
• Study First Submitted QC: 2021-02-08
• Study First Posted: 2021-02-11
• Study Start: 2021-02-15
• Primary Completion: 2021-07-06
• Study Completion: 2021-07-06
• Results First Submitted: 2022-06-29
• Status Verified: 2023-05
• Results First Submitted QC: 2023-05-21
• Last Update Submitted: 2023-05-21
• Results First Posted: 2024-02-01
• Last Update Posted: 2024-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

• Are overtly healthy
• Body mass index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m²)

Exclusion Criteria

• have known allergies to lasmiditan, dabigatran, rosuvastatin-related compounds or any components of the formulation of lasmiditan, dabigatran, rosuvastatin, or a history of significant atopy
• have an abnormal blood pressure and/or pulse rate as determined by the investigator
• have clinically significant abnormalities on electrocardiogram (ECG) as determined by investigator
• have a history or presence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study interventions; or of interfering with the interpretation of data. Appendectomy, splenectomy, and cholecystectomy are considered as acceptable
• have any medical conditions, medical history, or are taking any medications that are contraindicated in the dabigatran etexilate or rosuvastatin label
• are intending to use over-the-counter or prescription medication, including dietary supplements, traditional medicines, and herbal supplements, within 14 days prior to dosing and until study discharge (apart from occasional acetaminophen, hormonal contraception, or hormone replacement therapy)
• currently use or show evidence of substance abuse (including alcohol abuse) or dependence within the past 6 months based on history at screening
• Part 1 Only: have known bleeding disorder including prior personal or familial history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder or abnormal coagulation test (prothrombin time/international normalized ratio [INR] or partial thromboplastin time/activated partial thromboplastin time greater than upper limit of normal [ULN]) result at screening
• Part 2 only: have c.34AA, c.421AA, or c.34GA/421CA genotypes of ABCG2 as determined through genotyping

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
10 mg Rosuvastatin + 200 mg Lasmiditan - Part 2	Rosuvastatin	Participants received 10 mg rosuvastatin on Day 1 followed by 200 mg lasmiditan QD on Days 8 and 9, and 10 mg of rosuvastatin along with 200 mg lasmiditan on Day 10. All treatments were administered orally.
10 mg Rosuvastatin + 200 mg Lasmiditan - Part 2	Lasmiditan	Participants received 10 mg rosuvastatin on Day 1 followed by 200 mg lasmiditan QD on Days 8 and 9, and 10 mg of rosuvastatin along with 200 mg lasmiditan on Day 10. All treatments were administered orally.
150 Milligram (mg) Dabigatran Etexilate + 200mg Lasmiditan - Part 1	Dabigatran Etexilate	Participants received 150 mg dabigatran etexilate on Day 1 followed by 200 mg lasmiditan once daily (QD) on Days 8 and 9, and 150 mg of dabigatran etexilate along with 200 mg lasmiditan on Day 10. All treatments were administered orally
150 Milligram (mg) Dabigatran Etexilate + 200mg Lasmiditan - Part 1	Lasmiditan	Participants received 150 mg dabigatran etexilate on Day 1 followed by 200 mg lasmiditan once daily (QD) on Days 8 and 9, and 150 mg of dabigatran etexilate along with 200 mg lasmiditan on Day 10. All treatments were administered orally

Primary Outcome Measures

Name	Time	Method
Part 2 PK: Cmax of Rosuvastatin to Assess Breast Cancer Resistance Protein (BCRP) Activity.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.	PK: Cmax of Rosuvastatin.
Part 1 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran to Assess P-glycoprotein (P-gp) Activity.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.	PK: Cmax of Dabigatran.
Part 1 PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] ) of Dabigatran to Assess P-gp Activity.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.	PK: AUC\[0-∞\] of Dabigatran
Part 2 PK: AUC[0-∞] of Rosuvastatin to Assess BCRP Activity.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.	PK: AUC\[0-∞\] of Rosuvastatin

Trial Locations

Locations (1)

Lilly Centre for Clinical Pharmacology; 🇸🇬 Singapore, Singapore