Healthy
Conditions
Keywords
Drug Interaction Study
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.
Interventions
DRUGLasmiditan
Administered orally.
DRUGDabigatran Etexilate
Administered orally.
DRUGRosuvastatin
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 |
Countries
Singapore
Participant flow
Pre-assignment details
This study consisted of two parts - Part 1 and Part 2, each consisting of two periods. Part 1 studied dabigatran P-glycoprotein (P-gp) drug-drug interaction with lasmiditan. Part 2 studied rosuvastatin breast cancer resistance protein (BCRP) drug-drug interaction with lasmiditan.
Participants by arm
| Arm | Count |
|---|---|
| 150 mg Dabigatran Etexilate-Part 1 Period 1 Participants received a single oral dose 150 mg dabigatran etexilate on Day 1. | 66 |
| 10 mg Rosuvastatin-Part 2 Period 1 Participants received a single oral dose of 10 mg rosuvastatin on Day 1. | 30 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 10 mg Rosuvastatin-Part 2 Period 1 | 150 mg Dabigatran Etexilate-Part 1 Period 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 65 Participants | 95 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 64 Participants | 93 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Singapore | 30 Participants | 66 Participants | 96 Participants |
| Sex: Female, Male Female | 6 Participants | 25 Participants | 31 Participants |
| Sex: Female, Male Male | 24 Participants | 41 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 64 | 0 / 64 | 0 / 30 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 14 / 66 | 44 / 64 | 30 / 64 | 6 / 30 | 17 / 30 | 9 / 30 |
| serious Total, serious adverse events | 0 / 66 | 0 / 64 | 0 / 64 | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Part 1 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran to Assess P-glycoprotein (P-gp) Activity.
PK: Cmax of Dabigatran.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.
Population: All participants from Part 1 who received at least 1 dose of Dabigatran etexilate and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg Dabigatran Etexilate (Part 1 Period 1) | Part 1 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran to Assess P-glycoprotein (P-gp) Activity. | 138 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 55 |
| 150 mg Dabigatran Etexilate + 200 mg Lasmiditan (Part 1 Period 2) | Part 1 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran to Assess P-glycoprotein (P-gp) Activity. | 168 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
Primary
Part 1 PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] ) of Dabigatran to Assess P-gp Activity.
PK: AUC\[0-∞\] of Dabigatran
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.
Population: All participants from Part 1 who received at least 1 dose of Dabigatran etexilate had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg Dabigatran Etexilate (Part 1 Period 1) | Part 1 PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] ) of Dabigatran to Assess P-gp Activity. | 1240 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 53 |
| 150 mg Dabigatran Etexilate + 200 mg Lasmiditan (Part 1 Period 2) | Part 1 PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] ) of Dabigatran to Assess P-gp Activity. | 1540 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50 |
Primary
Part 2 PK: AUC[0-∞] of Rosuvastatin to Assess BCRP Activity.
PK: AUC\[0-∞\] of Rosuvastatin
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.
Population: All participants from Part 2 who received at least 1 dose of Rosuvastatin and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg Dabigatran Etexilate (Part 1 Period 1) | Part 2 PK: AUC[0-∞] of Rosuvastatin to Assess BCRP Activity. | 58.6 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 60 |
| 150 mg Dabigatran Etexilate + 200 mg Lasmiditan (Part 1 Period 2) | Part 2 PK: AUC[0-∞] of Rosuvastatin to Assess BCRP Activity. | 67.3 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 52 |
Primary
Part 2 PK: Cmax of Rosuvastatin to Assess Breast Cancer Resistance Protein (BCRP) Activity.
PK: Cmax of Rosuvastatin.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.
Population: All participants from Part 2 who received at least 1 dose of Rosuvastatin and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg Dabigatran Etexilate (Part 1 Period 1) | Part 2 PK: Cmax of Rosuvastatin to Assess Breast Cancer Resistance Protein (BCRP) Activity. | 8.23 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| 150 mg Dabigatran Etexilate + 200 mg Lasmiditan (Part 1 Period 2) | Part 2 PK: Cmax of Rosuvastatin to Assess Breast Cancer Resistance Protein (BCRP) Activity. | 8.85 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |