Healthy
Conditions
Brief summary
The main purpose of this study is to learn about how H2 antagonist (ranitidine) and proton pump inhibitor (PPI) (omeprazole) affect Selpercatinib in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 9 weeks, inclusive of screening period.
Interventions
DRUGSelpercatinib
Administered orally.
DRUGRanitidine
Administered orally.
DRUGOmeprazole
Administered orally.
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female participants of non-childbearing potential who are agreeable to take birth control measures until study completion * Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening * Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
Exclusion criteria
* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study * Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening * Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of Period 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: AUC0-t of Selpercatinib. The analysis of variance (ANOVA) model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric least squares (LS) means and the difference between treatment geometric LS means, as well as their corresponding 90% confidence intervals (CIs). The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses. |
| PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: AUC0-inf of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses. |
| PK: Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: %AUCextrap of Selpercatinib |
| PK: Maximum Observed Plasma Concentration (Cmax) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: Cmax of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses. |
| PK: Time of Maximum Observed Concentration (Tmax) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: Tmax of Selpercatinib |
| PK: Apparent Volume of Distribution (Vz/F) | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: Vz/F of Selpercatinib |
| PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: CL/F of Selpercatinib |
| PK: Apparent Terminal Elimination Half-life (t½) of Selpercatinib | PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3 | PK: t½ of Selpercatinib |
Countries
United States
Participant flow
Pre-assignment details
This is a fixed sequence study where participants receive Selpercatinib in Period 1, Selpercatinib in combination with Ranitidine in Period 2, and Selpercatinib in combination with Omeprazole in Period 3.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants received a single oral dose of 160 mg Selpercatinib (Study Day 1).
Participants received 150 mg ranitidine twice a day orally for 11 days (Study Days 8 to 18) with a single oral dose of 160 mg Selpercatinib (Study Day 12).
Participants received 40 mg omeprazole once daily for 11 days (Study Days 19 to 29) with a single oral dose of 160 mg Selpercatinib (Study Day 23). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 2 - Day 8 to Day 19 | Adverse Event | 0 | 1 | 0 |
| Period 2 - Day 8 to Day 19 | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 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 | 11 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 | 9 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 17 |
| other Total, other adverse events | 5 / 20 | 11 / 20 | 4 / 17 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 17 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib
PK: AUC0-t of Selpercatinib. The analysis of variance (ANOVA) model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric least squares (LS) means and the difference between treatment geometric LS means, as well as their corresponding 90% confidence intervals (CIs). The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for AUC0-t.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 21600 hour*nanograms per milliliter(h*ng/mL) | Geometric Coefficient of Variation 31.4 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 19100 hour*nanograms per milliliter(h*ng/mL) | Geometric Coefficient of Variation 31.9 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 21000 hour*nanograms per milliliter(h*ng/mL) | Geometric Coefficient of Variation 27.4 |
Comparison: Fasted State90% CI: [0.797, 1.02]ANOVA
Comparison: Fed state90% CI: [0.876, 1.12]ANOVA
Primary
PK: Apparent Terminal Elimination Half-life (t½) of Selpercatinib
PK: t½ of Selpercatinib
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for t½.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | PK: Apparent Terminal Elimination Half-life (t½) of Selpercatinib | 24.4 hour | Geometric Coefficient of Variation 35.4 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Apparent Terminal Elimination Half-life (t½) of Selpercatinib | 29.3 hour | Geometric Coefficient of Variation 33.5 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Apparent Terminal Elimination Half-life (t½) of Selpercatinib | 27.4 hour | Geometric Coefficient of Variation 30.1 |
Primary
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib
PK: CL/F of Selpercatinib
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib | 7.35 liter per hour (L/h) | Geometric Coefficient of Variation 31.2 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib | 8.03 liter per hour (L/h) | Geometric Coefficient of Variation 33.5 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib | 7.58 liter per hour (L/h) | Geometric Coefficient of Variation 27.4 |
Primary
PK: Apparent Volume of Distribution (Vz/F)
PK: Vz/F of Selpercatinib
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | PK: Apparent Volume of Distribution (Vz/F) | 259 liter | Geometric Coefficient of Variation 44.2 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Apparent Volume of Distribution (Vz/F) | 331 liter | Geometric Coefficient of Variation 59.1 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Apparent Volume of Distribution (Vz/F) | 300 liter | Geometric Coefficient of Variation 48.6 |
Primary
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib
PK: AUC0-inf of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib | 21800 h*ng/mL | Geometric Coefficient of Variation 31.2 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib | 19900 h*ng/mL | Geometric Coefficient of Variation 33.5 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib | 21100 h*ng/mL | Geometric Coefficient of Variation 27.4 |
Comparison: Fasted state90% CI: [0.829, 1.05]ANOVA
Comparison: Fed State90% CI: [0.888, 1.13]ANOVA
Primary
PK: Maximum Observed Plasma Concentration (Cmax) of Selpercatinib
PK: Cmax of Selpercatinib. The ANOVA model was performed on the natural log (ln)-transformed PK parameters and included calculation of geometric LS means and the difference between treatment geometric LS means, as well as their corresponding 90% CIs. The ratios of geometric LS mean and 90% CI for the ratio of the PK parameter for each comparison was constructed using the exponentiation of the difference and the CIs from the ANOVA analyses.
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib | PK: Maximum Observed Plasma Concentration (Cmax) of Selpercatinib | 1650 ng/mL | Geometric Coefficient of Variation 58.4 |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Maximum Observed Plasma Concentration (Cmax) of Selpercatinib | 1330 ng/mL | Geometric Coefficient of Variation 67.8 |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Maximum Observed Plasma Concentration (Cmax) of Selpercatinib | 1220 ng/mL | Geometric Coefficient of Variation 63.4 |
Comparison: Fasted State90% CI: [0.68, 0.985]ANOVA
Comparison: Fed state90% CI: [0.645, 0.949]ANOVA
Primary
PK: Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of Selpercatinib
PK: %AUCextrap of Selpercatinib
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for %AUCextrap.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 160 mg Selpercatinib | PK: Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of Selpercatinib | 0.337 percentage of (%) of AUCextrap |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of Selpercatinib | 0.818 percentage of (%) of AUCextrap |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of Selpercatinib | 0.612 percentage of (%) of AUCextrap |
Primary
PK: Time of Maximum Observed Concentration (Tmax) of Selpercatinib
PK: Tmax of Selpercatinib
Time frame: PK: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 post Selpercatinib dose on Day 1 - Period 1, Day 12 - Period 2, and Day 23 - Period 3
Population: All enrolled or randomized participants who received at least one dose of study drug with evaluable data for tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 160 mg Selpercatinib | PK: Time of Maximum Observed Concentration (Tmax) of Selpercatinib | 2.00 hour |
| 150 mg Ranitidine Dosed With 160 mg Selpercatinib | PK: Time of Maximum Observed Concentration (Tmax) of Selpercatinib | 1.83 hour |
| 40 mg Omeprazole Dosed With 160 mg Selpercatinib | PK: Time of Maximum Observed Concentration (Tmax) of Selpercatinib | 3.00 hour |