The Effect of AMG 133 on Gastric Emptying

A Phase 1, Randomized, Double Blind, Multiple Dose, Placebo-controlled, Parallel Group Study to Evaluate the Impact of AMG 133 on Gastric Emptying in Participants Living With Overweight or Obesity

The primary objective of the trial is to evaluate the effect of AMG 133 versus placebo on acetaminophen pharmacokinetics (PK), a marker for gastric emptying, in participants living with overweight or obesity.

Study Overview

• Status: Completed
• Conditions: Overweight or Obesity
• Intervention / Treatment: Drug: Acetaminophen; Drug: Placebo; Drug: AMG 133

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female participants between 18 and 65 years of age.

  a. Females must not be pregnant or lactating.

• Body mass index between ≥ 27 to < 40 kg/m^2.

Exclusion Criteria:

• History or evidence of clinically significant disorder, condition, or disease not otherwise excluded that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• History of or active diabetes or Hemoglobin A1C ≥ 6.5% (≥ 48 mmol/mol).
• History or evidence of endocrine disorder.
• History of acute or chronic pancreatitis within 1 year, or elevation in serum lipase/amylase (> 2 x the upper limit of normal [ULN]), or fasting serum triglyceride level of > 500 mg/dL.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• Uncontrolled thyroid disease.
• History of or current signs of gastroparesis.
• History or current signs or symptoms of cardiovascular disease.
• History suggestive of esophageal, gastric, or duodenal ulceration or bowel disease; or a history of gastrointestinal surgery other than uncomplicated appendectomy or hernia repair.
• History of gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, gastric/jejunal tube feeds, or uncontrolled inflammatory gastrointestinal disease.
• History of hypersensitivity, intolerance, or allergy to AMG 133 or related/similar compounds or acetaminophen or their ingredients.
• Any contraindication to acetaminophen according to the applicable labelling.
• Inability to swallow oral medication.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x the upper limit of normal.
• Use of any over-the-counter or prescription medications within 30 days or 5 half-lives.
• 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.
• Current or prior use of all herbal medicines (e.g., St. John's wort), vitamins, and supplements consumed by the participant within the 30 days prior to enrollment.
• Participant has received a dose of an investigational medicinal product (IMP) within the past 30 days or 5 half-lives.
• Have previously completed or withdrawn from this study or any other study investigating AMG 133 or have previously received the IMP.
• Current use of acute or chronic medication known to affect gastric emptying.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 133; Participants will receive AMG 133 subcutaneously (SC) and acetaminophen orally.	Drug: Acetaminophen; Acetaminophen will be administered orally.; Drug: AMG 133; AMG 133 will be administered SC.; Other Names: Maridebart cafraglutide
Placebo Comparator: Placebo; Participants will receive placebo SC and acetaminophen orally.	Drug: Acetaminophen; Acetaminophen will be administered orally.; Drug: Placebo; Placebo will be administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) for Acetaminophen	Days 1, 3, 8, 17, 31, 59, 64, and 86
Time to Cmax (Tmax) for Acetaminophen	Days 1, 3, 8, 17, 31, 59, 64, and 86
Area Under the Plasma Concentration-time Curve (AUC) from Time Zero to Time of Last Quantifiable Concentration (AUClast) for Acetaminophen	Days 1, 3, 8, 17, 31, 59, 64, and 86
AUC from Time Zero to Infinity (AUCinf) for Acetaminophen	Days 1, 3, 8, 17, 31, 59, 64, and 86
AUC from Time Zero to 5 Hours (AUC5hr) for Acetaminophen	Days 1, 3, 8, 17, 31, 59, 64, and 86

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for AMG 133		Days 1 to 9, 15 to 18, 22, 29 to 32, 36, 44, 57 to 65, 72, 85 to 87, 100, and 128
AUClast for AMG 133		Days 1 to 9, 15 to 18, 22, 29 to 32, 36, 44, 57 to 65, 72, 85 to 87, 100, and 128
AUCinf for AMG 133		Days 1 to 9, 15 to 18, 22, 29 to 32, 36, 44, 57 to 65, 72, 85 to 87, 100, and 128
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)		Day 1 to Day 128
Number of Participants Who Experience Serious Adverse Events (SAEs)		Screening (Day -28) to Day 128
Change from Baseline in Food Intake and Appetite	Change in Food intake during the ad libitum lunch and appetite visual analogue scale (VAS) scores in participants receiving AMG 133 and placebo will be evaluated.	Baseline to Day 64
Number of Participants Who Develop Anti-AMG 133 Antibodies		Day 2 up to Day 128

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): April 17, 2025
• Primary Completion (Actual): November 26, 2025
• Study Completion (Actual): November 26, 2025

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Overweight; AMG 133; MariTide
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Acetaminophen
• Other Study ID Numbers: 20230012

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