A Trial to Evaluate Interactions Between Antiemetic Medication and AMG 133 in Participants Living With Overweight or Obesity

A Phase 1, Randomized, Open-label, Parallel-group, Drug-drug Interaction Study to Evaluate the Effect of Antiemetic Medication on the Pharmacokinetics of AMG 133 in Participants Living With Overweight or Obesity

The primary objective of this trial is to evaluate the pharmacokinetics (PK) of AMG 133 administered alone and in combination with an antiemetic medication, ondansetron, in participants living with overweight or obesity.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: AMG 133; Drug: Ondansetron

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720
      • CenExel Collaborative Neuroscience Research, LLC Los Alamitos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Male or female participants, between 18 and 65 years of age.
2. Body mass index > 25 kg/m^2.

Exclusion Criteria

1. History or evidence of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator, would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion.
2. History of or active diabetes or hemoglobin A1C > 6.5%.
3. History or evidence of endocrine disorder.
4. History of acute or chronic pancreatitis within 1 year, or elevation in serum lipase/amylase (> 2 x upper limit of normal [ULN]), or fasting serum triglyceride level of > 500 mg/dL.
5. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
6. Uncontrolled thyroid disease.
7. History or current signs or symptoms of cardiovascular disease.
8. A QT interval corrected for heart rate based on the Fridericia's method (QTcF) interval > 450 msec in male participants or > 470 msec in female participants or history/evidence of long QT syndrome.
9. History of hypersensitivity, intolerance, or allergy to AMG 133 or its ingredients.
10. Any contraindication to ondansetron ODT according to the applicable labelling.
11. Alanine aminotransferase or aspartate aminotransferase > 2 x the ULN.
12. Use of any over-the-counter or prescription medications within 30 days or 5 half-lives (whichever is longer) before check-in.
13. Current use or prior use of any glucagon-like peptide 1 receptor (GLP-1R) agonist, or glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist or antagonist within the past 3 months.
14. Participant has received a dose of an investigational medicinal product (IMP) within the past 30 days or 5 half-lives.
15. Have previously completed or withdrawn from this trial or any other trial investigating AMG 133 or have previously received the IMP.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose AMG 133 without Ondansetron; Participants will receive a single subcutaneous (SC) low dose of 70 mg AMG 133.	Drug: AMG 133; AMG 133 will be administered SC.
Experimental: High Dose AMG 133 without Ondansetron; Participants will receive a single SC high dose of 350 mg AMG 133.	Drug: AMG 133; AMG 133 will be administered SC.
Experimental: Low Dose AMG 133 with Ondansetron; Participants will receive a single SC low dose of 70 mg AMG 133 and ondansetron 8 mg orally disintegrating tablet (ODT) every 8 hours for 72 hours.	Drug: AMG 133; AMG 133 will be administered SC.; Drug: Ondansetron; Ondansetron will be administered via ODT.
Experimental: High Dose AMG 133 with Ondansetron; Participants will receive a single SC high dose of 350 mg AMG 133 and ondansetron 8mg ODT every 8 hours for 72 hours.	Drug: AMG 133; AMG 133 will be administered SC.; Drug: Ondansetron; Ondansetron will be administered via ODT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of AMG 133	Up to Day 120
Area Under the Plasma Concentration-time Curve (AUC) from Time Zero to Time of Last Quantifiable Concentration (AUClast) of AMG 133	Up to Day 120
AUC from Time Zero to Infinity (AUCinf) of AMG 133	Up to Day 120

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to Day 120
Number of Participants with Serious AEs (SAEs)	Up to Day 120
Number of Participants with Anti-AMG 133 Antibodies	Up to Day 120

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): December 10, 2024
• Primary Completion (Actual): May 9, 2025
• Study Completion (Actual): May 9, 2025

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Overweight; Ondansetron; AMG 133; Drug-drug Interaction; Antiemetic
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Imidazoles; Indoles; Heterocyclic Compounds, 3-Ring; Carbazoles; Ondansetron
• Other Study ID Numbers: 20210281

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 (or other new use) 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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