Healthy
Conditions
Brief summary
The main purpose of this study is to determine the effect of selpercatinib on the levels of dabigatran in the blood stream and how long it takes the body to remove dabigatran. This study will also look at how safe and well-tolerated of dabigatran when administered in combination with selpercatinib in healthy participants. This study will last approximately 22 to 25 days.
Interventions
DRUGDabigatran
Administered orally.
DRUGSelpercatinib
Administered orally.
Sponsors
Eli Lilly and Company
Loxo Oncology, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males or females, as determined by medical history, physical examination and vital signs. * Body mass index (BMI) within the range of 19 to 35 kilograms per meter squared (kg/m²) * Male participants are not required to adhere to contraceptive requirements and female participants of childbearing potential must agree to be either remain abstinent or stay in a same sex relationship without sexual relationships with males or must agree to use a highly effective method of contraception and who underwent bilateral salpingectomy. The Female participants not of childbearing potential are not required to use contraception.
Exclusion criteria
* Have a positive pregnancy test at screening or Day -1, where applicable * Are planning to become pregnant during the study or within 1 month of study completion * Are women who are lactating * Have known allergies to selpercatinib- or dabigatran-related compounds or any components of the formulation of selpercatinib or dabigatran, or history of significant atopy * Have a history of allergic reactions to medications or food products * Have a clinically significant abnormality of blood pressure and/or pulse rate as determined by the investigator * Have known bleeding disorder including prior personal or familiar history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder * Clinically significant abnormalities on ECG as determined by the investigator or prolongation of the QTcB or QTcF \>450 msec on more than 1 ECG obtained during screening only * Have clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to the planned start of selpercatinib * Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study * Have an average weekly alcohol intake that exceeds 21 units per week (males ≤65 years old) and 14 units per week (females); 1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirit(s) * Are smokers of more than 10 cigarettes or e-cigarettes, or 3 cigars or 3 pipes, per day * Consume excessive amounts of coffee, tea, cola, or other caffeinated beverages per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran | Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours (h) postdose | PK: Cmax of Dabigatran |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Dabigatran | Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose | PK: AUC(0-inf) of Dabigatran |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Cmax of Selpercatinib | Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose | PK: Cmax of Selpercatinib |
| PK: AUC(0-inf) of Selpercatinib | Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose | PK: AUC(0-inf) of Selpercatinib |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Selpercatinib | Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose | PK: Tmax of Selpercatinib |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran + Selpercatinib Participants received a single oral dose of 150 milligrams (mg) dabigatran on Day 1 and a single oral dose of 150 mg dabigatran coadministered with a single oral dose of 2 x 80 mg (160 mg) Selpercatinib on Day 8. There was a washout period of 7 days between dosing on Days 1 and 8. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Family Emergency | 1 |
Baseline characteristics
| Characteristic | Dabigatran + Selpercatinib |
|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 36 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 35 |
| other Total, other adverse events | 0 / 36 | 0 / 35 |
| serious Total, serious adverse events | 0 / 36 | 0 / 35 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran
PK: Cmax of Dabigatran
Time frame: Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours (h) postdose
Population: All participants who received at least one dose of dabigatran and had evaluable PK.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran | 192 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Selpercatinib + Dabigatran | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran | 276 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
90% CI: [1.33, 1.55]Mixed Models Analysis
Primary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Dabigatran
PK: AUC(0-inf) of Dabigatran
Time frame: Day 1 and Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
Population: All participants who received at least one dose of dabigatran had evaluable PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Dabigatran | 1650 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 42 |
| Selpercatinib + Dabigatran | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Dabigatran | 2290 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 37 |
90% CI: [1.3, 1.46]Mixed Models Analysis
Secondary
PK: AUC(0-inf) of Selpercatinib
PK: AUC(0-inf) of Selpercatinib
Time frame: Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
Population: All participants who received at least one dose of Selpercatinib and had evaluable PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran | PK: AUC(0-inf) of Selpercatinib | 25600 ng*h/mL | Geometric Coefficient of Variation 27 |
Secondary
PK: Cmax of Selpercatinib
PK: Cmax of Selpercatinib
Time frame: Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
Population: All participants who received at least one dose of Selpercatinib and had evaluable PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran | PK: Cmax of Selpercatinib | 1830 ng/mL | Geometric Coefficient of Variation 23 |
Secondary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Selpercatinib
PK: Tmax of Selpercatinib
Time frame: Day 8: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h postdose
Population: All participants who received at least one dose of Selpercatinib and had evaluable PK.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dabigatran | PK: Time of Maximum Observed Drug Concentration (Tmax) of Selpercatinib | 3.00 hours |