A Study of the Absorption, Metabolism, and Excretion of [14C]-AMG 510 Following a Single Oral Dose in Healthy Male Subjects

A Phase I, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-AMG 510 Following a Single Oral Dose in Healthy Male Subjects

The primary objectives of the study are: to characterize the primary route(s) of elimination of [14C]-AMG 510 and drug-related material, and estimate the overall recovery of radiolabeled material in healthy male participants after oral administration of [14C]-AMG 510, and to characterize the pharmacokinetic (PK) of total radioactivity and AMG 510 following a single oral dose of [14C]-AMG 510 in healthy male participants.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AMG 510

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male participants between 18 and 55 years of age (inclusive) at the time of Screening.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations as assessed by the Investigator (or designee).
• Body mass index between 18 and 30 kg/m2 (inclusive) at the time of Screening.
• History of a minimum of 1 bowel movement per day.

Exclusion Criteria:

• History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome); or a history of gastrointestinal surgery other than uncomplicated appendectomy.
• Inability to swallow oral medication or history of malabsorption syndrome.
• History of significant 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 of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
• Participant has received a dose of an investigational drug (new chemical entity) within the past 90 days or 5 half-lives, whichever is longer, prior to Check-in.
• Participants with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in.
• Participants who have participated in a radiolabeled drug study where exposures are known to the Investigator within the previous 4 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the Investigator within the previous 6 months prior to admission to the clinic for this study. The total 12-month exposure from this study and a maximum of 2 other previous radiolabeled studies within 4 to 12 months prior to this study will be within the Code of Federal Regulations (CFR)-recommended levels considered safe, per US Title 21 CFR 361.1: less than 5000 mrem whole body annual exposure with consideration given to the half-lives of the previous radiolabeled study drugs received.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG510; Each participant will receive a single oral dose of AMG510 on Day 1 after an overnight fast.	Drug: AMG 510; Single oral dose of AMG510.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve (AUC) from time zero to infinity (AUCinf)	Day 1 to Day 14
AUC from time zero to the last quantifiable concentration (AUClast)	Day 1 to Day 14
Maximum observed concentration (Cmax)	Day 1 to Day 14
Time of Cmax (tmax)	Day 1 to Day 14
Apparent terminal elimination half-life (t1/2)	Day 1 to Day 14
Total clearance (AMG 510 only; CL/F)	Day 1 to Day 14
Volume of distribution (AMG 510 only; Vz/F)	Day 1 to Day 14
Plasma AMG 510 to total radioactivity ratio	Day 1 to Day 14
Whole blood to plasma total radioactivity ratio	Day 1 to Day 14
Amount (Aeu) of AMG510 excreted in urine	Day 1 to Day 14
Percentage (feu) of AMG510 excreted in urine	Day 1 to Day 14
Renal clearance (CLR) of AMG510	Day 1 to Day 14
Amount (Aef) of AMG510 excreted in feces	Day 1 to Day 14
Percentage (fef) of AMG510 excreted in feces	Day 1 to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolite profile of AMG 510		Day 1 to Day 14
Identification of AMG 510 metabolites		Day 1 to Day 14
Incidence of adverse events	Adverse events will be graded by severity. Laboratory abnormalities (hematology, clinical chemistry, and urinalysis test results) will be recorded as adverse events, in addition to abnormalities in vital signs and physical examinations.	Up to approximately 6 weeks
QTc interval measured by 12-lead electrocardiogram (ECG)		Up to approximately 6 weeks

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): March 24, 2020
• Study Completion (Actual): March 24, 2020

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Healthy volunteers; AMG 510
• Other Study ID Numbers: 20190321

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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