Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants

A Phase I, Open-label, Fixed Sequence Crossover Study to Investigate the Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin, a Breast Cancer Resistance Protein Substrate, in Healthy Subjects

A study to determine the effect of sotorasib on the pharmacokinetics (PK) of rosuvastatin, and to assess the PK of rosuvastatin when administered alone, in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Sotorasib

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117-5116
      • Covance Clinical Research Unit - Daytona Beach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Healthy male subjects or female subjects, between 18 and 60 years of age (inclusive), at the time of Screening.
• Body mass index, between 18 and 30 kg/m2 (inclusive), at the time of Screening.
• Females of nonchildbearing potential

Exclusion criteria:

• Inability to swallow oral medication or history of malabsorption syndrome.
• History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor.
• Poor peripheral venous access.
• History or evidence, at Screening or Check in, of clinically significant disorder, condition, or disease, including history of myolysis, not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin alone	Drug: Rosuvastatin; Oral dose
Experimental: Rosuvastatin + sotorasib	Drug: Rosuvastatin; Oral dose; Drug: Sotorasib; Oral dose; Other Names: AMG 510

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin	The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin	The PK parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin	The PK parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs)	Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms (ECGs), and vital signs results were recorded as AEs.	Day 1 to Day 41
Cmax of Sotorasib	The PK parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6
AUClast of Sotorasib	The PK parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6
AUCinf of Sotorasib	The PK parameters were determined using standard non-compartmental methods.	Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): October 10, 2021
• Study Completion (Actual): October 10, 2021

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Healthy participants; Rosuvastatin; Sotorasib; AMG 510
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Checkpoint Inhibitors; Rosuvastatin Calcium; Sotorasib
• Other Study ID Numbers: 20200426

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No