An Open-Label, 3-Period, Fixed Sequence Study to Evaluate the Effect of an H2 Antagonist and a Proton Pump Inhibitor on the Single Dose Pharmacokinetics of LOXO-292 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Selpercatinib
- Conditions
- Healthy
- Sponsor
- Eli Lilly and Company
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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- •Have previously participated or withdrawn from this study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
Arms & Interventions
160 milligram (mg) Selpercatinib
Participants received a single oral dose of 160 mg Selpercatinib (Study Day 1).
Intervention: Selpercatinib
150 mg Ranitidine dosed with 160 mg Selpercatinib
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).
Intervention: Selpercatinib
150 mg Ranitidine dosed with 160 mg Selpercatinib
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).
Intervention: Ranitidine
40 mg Omeprazole dosed with 160 mg Selpercatinib
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).
Intervention: Selpercatinib
40 mg Omeprazole dosed with 160 mg Selpercatinib
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).
Intervention: Omeprazole
Outcomes
Primary Outcomes
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) 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
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
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
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
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
PK: %AUCextrap of Selpercatinib
PK: Maximum Observed Plasma Concentration (Cmax) 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
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
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
PK: Tmax of Selpercatinib
PK: Apparent Volume of Distribution (Vz/F)
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
PK: Vz/F of Selpercatinib
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (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
PK: CL/F of Selpercatinib
PK: Apparent Terminal Elimination Half-life (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
PK: t½ of Selpercatinib