Healthy
Conditions
Brief summary
The main purpose of this study is to compare the amount of selpercatinib that gets into the blood stream and how long it takes the body to get rid of it, when given as different formulations. The information about any adverse effects experienced will be collected and the tolerability of selpercatinib will also be evaluated. The study may last up to 56 days including the 28 days of screening period.
Interventions
DRUGSelpercatinib
Administered orally
Sponsors
Eli Lilly and Company
Loxo Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and vital signs. * Participants who have clinical laboratory test results within the normal reference range for the population or investigative site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
Exclusion criteria
* 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 * Clinically significant abnormalities on ECG as determined by the investigator or prolongation of the QTcB or QTcF \>450 msec at screening * Have clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to the planned start of selpercatinib * 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 investigational product; or of interfering with the interpretation of data. Appendectomy, splenectomy, and cholecystectomy are considered as acceptable * Use of H2 blockers, proton pump inhibitors, and other drugs that affect selpercatinib exposure within 7 days of screening * Are intending to use over-the-counter or prescription medication, including dietary supplements, within 14 days prior to dosing and until study discharge (apart from occasional acetaminophen (≤2 g/24 hours), hormonal contraception, or hormone replacement therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose; | PK: Cmax of Selpercatinib |
| PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Selpercatinib | Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose; | PK: AUC\[0-∞\] of Selpercatinib. |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Selpercatinib | Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose; | PK: AUC\[0-tlast\] of Selpercatinib |
Countries
United States
Participant flow
Pre-assignment details
This study included a washout period of 14 days between doses of selpercatinib.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 - Selpercatinib Reference/Test Sequence 1: 160 mg selpercatinib (2 x 80 mg capsules) Reference/160 mg selpercatinib (1 x 160 mg tablet) Test | 112 |
| Sequence 2: Selpercatinib Test/Reference Sequence 2: 160 mg selpercatinib (1 x 160 mg tablet) Test/160 mg selpercatinib (2 x 80 mg capsules) Reference | 112 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 |
| Period 2 | Adverse Event | 4 | 2 |
| Period 2 | Lost to Follow-up | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 |
| Washout Period | Adverse Event | 3 | 4 |
| Washout Period | Lost to Follow-up | 1 | 0 |
| Washout Period | Physician Decision | 2 | 0 |
| Washout Period | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Sequence 1 - Selpercatinib Reference/Test | Total | Sequence 2: Selpercatinib Test/Reference |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.3 | 42.5 years STANDARD_DEVIATION 12.3 | 42.8 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 71 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants | 153 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 82 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 126 Participants | 67 Participants |
| Region of Enrollment United States | 112 participants | 224 participants | 112 participants |
| Sex: Female, Male Female | 53 Participants | 106 Participants | 53 Participants |
| Sex: Female, Male Male | 59 Participants | 118 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 216 | 0 / 212 |
| other Total, other adverse events | 0 / 216 | 0 / 212 |
| serious Total, serious adverse events | 0 / 216 | 0 / 212 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Selpercatinib
PK: AUC\[0-tlast\] of Selpercatinib
Time frame: Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose;
Population: All participants who received at least one dose of selpercatinib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib (Reference) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Selpercatinib | 20200 ng*hr/mL | Geometric Coefficient of Variation 47 |
| 160 mg Selpercatinib (Test) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Selpercatinib | 18100 ng*hr/mL | Geometric Coefficient of Variation 65 |
94.12% CI: [0.834, 0.951]Mixed Models Analysis
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib
PK: Cmax of Selpercatinib
Time frame: Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose;
Population: All participants who received at least 1 dose of Selpercatinib and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib (Reference) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 1520 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61 |
| 160 mg Selpercatinib (Test) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 1350 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 91 |
94.12% CI: [0.81, 0.976]Mixed Models Analysis
Primary
PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Selpercatinib
PK: AUC\[0-∞\] of Selpercatinib.
Time frame: Day 1 and Day 15: Predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 312 hours (h) postdose;
Population: All participants who received at least one dose of selpercatinib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib (Reference) | PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Selpercatinib | 20700 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
| 160 mg Selpercatinib (Test) | PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Selpercatinib | 19300 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 51 |
94.12% CI: [0.882, 0.975]Mixed Models Analysis