Study of H2 Antagonist and a Proton Pump Inhibitor of Selpercatinib in Healthy Participants

NCT05338502 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 17574J2G-OX-JZJLLOXO-RET-19075
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• 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.

  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: 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.

  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: 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

  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: 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.

  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: Time of Maximum Observed Concentration (Tmax) of Selpercatinib

  PK: 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: Apparent Volume of Distribution (Vz/F)

  PK: Vz/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: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib

  PK: 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: Apparent Terminal Elimination Half-life (t½) of Selpercatinib

  PK: 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

Study Arms (3)

160 milligram (mg) Selpercatinib

EXPERIMENTAL

Participants received a single oral dose of 160 mg Selpercatinib (Study Day 1).

Drug: Selpercatinib

150 mg Ranitidine dosed with 160 mg Selpercatinib

EXPERIMENTAL

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).

Drug: Selpercatinib; Drug: Ranitidine

40 mg Omeprazole dosed with 160 mg Selpercatinib

EXPERIMENTAL

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).

Drug: Selpercatinib; Drug: Omeprazole

Interventions

Selpercatinib DRUG

Administered orally.

Also known as: LY3527723, LOXO-292

150 mg Ranitidine dosed with 160 mg Selpercatinib; 160 milligram (mg) Selpercatinib; 40 mg Omeprazole dosed with 160 mg Selpercatinib

Ranitidine DRUG

Administered orally.

150 mg Ranitidine dosed with 160 mg Selpercatinib

Omeprazole DRUG

Administered orally.

40 mg Omeprazole dosed with 160 mg Selpercatinib

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (1)

Covance Clinical Research Unit, Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

selpercatinib; Ranitidine; Omeprazole

Intervention Hierarchy (Ancestors)

Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: April 21, 2022
• Study Start: July 8, 2019
• Primary Completion: September 3, 2019
• Study Completion: September 3, 2019
• Last Updated: October 30, 2024
• Results First Posted: October 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)