Healthy
Conditions
Brief summary
The main purpose of this study is to determine the effect of pirtobrutinib on the levels of rosuvastatin in the blood stream in healthy participants. This study will also evaluate the safety and tolerability of rosuvastatin when administered in combination with pirtobrutinib in healthy participants. This study will last up to approximately 26 days excluding screening period.
Interventions
DRUGRosuvastatin
Administered Orally.
DRUGPirtobrutinib
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 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and vital signs. * Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per meter squared (kg/m²) and a body weight of at least 50 kg. * Males, or female participants who are not of childbearing potential.
Exclusion criteria
* Have known allergies to pirtobrutinib or rosuvastatin, related compounds, or any components of the formulation. * Have an abnormal blood pressure and/or pulse rate, deemed to be clinically significant by the investigator. * Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological, or psychiatric disorder or surgery (including cholecystectomy) capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data. * Have used or intend to use prescription or nonprescription medication (including dietary supplements, vitamins, and/or herbal medications), or modulators of CYP3A4 or BCRP within 7 days prior to dosing, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study. * Have c.34AA, c.421AA, or c.34GA/421CA genotypes of ABCG2 as determined through genotyping. * Have c.521TC and c/521CC genotypes of SLCO1B1 as determined by genotyping.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Rosuvastatin | Day 1, Day 6 and Day 13: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours (h) post-dose. | PK: Cmax of Rosuvastatin |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Rosuvastatin | Day 1, Day 6 and Day 13: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours (h) post-dose. | PK: AUC(0-inf) of Rosuvastatin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin + Pirtobrutinib Participants received study intervention through oral administration as follows:
* Day 1: 20 milligram (mg) rosuvastatin alone
* Day 6: 20 mg rosuvastatin co-administered with 200 mg pirtobrutinib
* Days 7 to 12: Once daily (QD) doses of 200 mg pirtobrutinib alone
* Day 13: 20 mg rosuvastatin co-administered with 200 mg pirtobrutinib
* Days 14 to 17: QD doses of 200 mg pirtobrutinib alone. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Rosuvastatin + Pirtobrutinib |
|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 15 Participants |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 27 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 3 / 32 | 1 / 32 | 3 / 32 | 0 / 31 | 1 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 31 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Rosuvastatin
PK: Cmax of Rosuvastatin
Time frame: Day 1, Day 6 and Day 13: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours (h) post-dose.
Population: All randomized participants who received at least one dose of rosuvastatin and had evaluable PK data for the respective days for this outcome analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rosuvastatin + Pirtobrutinib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Rosuvastatin | Day 1 | 9.45 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Rosuvastatin + Pirtobrutinib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Rosuvastatin | Day 6 | 23.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Rosuvastatin + Pirtobrutinib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Rosuvastatin | Day 13 | 23.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
Primary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Rosuvastatin
PK: AUC(0-inf) of Rosuvastatin
Time frame: Day 1, Day 6 and Day 13: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours (h) post-dose.
Population: All randomized participants who received at least one dose of rosuvastatin and had evaluable PK data for the respective days for this outcome analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rosuvastatin + Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Rosuvastatin | Day 1 | 88.2 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 44 |
| Rosuvastatin + Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Rosuvastatin | Day 6 | 189 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 41 |
| Rosuvastatin + Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Rosuvastatin | Day 13 | 207 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 40 |