A Research Study Investigating How Adults With Overweight or Obesity, With or Without Type 2 Diabetes, Tolerate Switching to a New Treatment (Zenagamtide) From Their Current Tirzepatide Medication

NCT07868354 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: NN9490-8554U1111-1330-4403
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this clinical study is to find out which zenagamtide dose can be switched to, from maintenance dose of tirzepatide in people with overweight or obesity, with or without type 2 diabetes (T2D). All participants will get tirzepatide and zenagamtide.

Conditions

Overweight; Obesity; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Number of treatment emergent adverse events (TEAE)

  Measured as number of events

  From first administration of zenagamtide day 1 to day 57

Secondary Outcomes (3)

• AUC: area under the zenagamtide plasma concentration-time curve

  From pre-dose on day 1 to day 8

• Cmax: the maximum observed plasma concentration of zenagamtide after first dose

  From pre-dose on day 1 to day 8

• tmax: time to maximum observed plasma concentration of zenagamtide after first dose

  From pre-dose on day 1 to day 8

Study Arms (1)

Tirzepatide and Zenagamtide

EXPERIMENTAL

Participants will receive one of the different dose levels of tirzepatide administered once weekly by subcutaneous injection. Following the last maintenance dose of tirzepatide, participants will switch to one of the different dose levels of zenagamtide administered once weekly by subcutaneous injection.

Drug: Tirzepatide; Drug: Zenagamtide

Interventions

Tirzepatide DRUG

Tirzeptide will be administered subcutaneously using pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.

Tirzepatide and Zenagamtide

Zenagamtide DRUG

Zenagamtide will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.

Tirzepatide and Zenagamtide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female (sex assigned at birth, inclusive of all gender identities).
• Age 18 years or older at the time of signing the informed consent.
• Considered eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.
• Participants on a stable treatment dose of tirzepatide for at least 4 weeks.
• Only for participants with T2D:
• Diagnosed with type 2 diabetes before screening.
• Treatment with 0-2 marketed oral glucose-lowering medications (metformin or sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a single agent or in combination) according to local label. Treatment with oral glucose-lowering medications must be stable (same drug(s), stable daily doses) for at least 90 days before screening.

You may not qualify if:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method.
• History of reduction in dose of tirzepatide, due to intolerability, without successful reescalation.
• Presence of any clinically relevant condition that causes symptoms which are similar to the gastrointestinal adverse events (GI AEs) linked to glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment, and which could confound evaluation of GLP-1 RA-related GI AEs and tolerability endpoints.
• Ongoing use of medications causing clinically relevant gastrointestinal symptoms that could confound evaluation of GLP-1 RA-related GI AEs and tolerability endpoints, as judged by the investigator.
• Use of prescription medicinal products or non-prescription drugs within 14 days before screening. Exceptions are:
• stable use (initiated minimum 30 days before screening) of statins, blood pressure lowering medicine, beta blockers
• highly effective contraceptives
• occasional use of paracetamol, ibuprofen and acetylsalicylic acid.
• Only for participants without T2D:
• \- Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions.
• Only for participants with T2D:
• Glycated haemoglobin (HbA1c) more than or equal to (≥) 10.5 percent (%) \[91 millimoles per mole (mmol/mol)\] at screening.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) within 180 days before screening or are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions, except conditions associated with diabetes mellitus.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (2)

PAREXEL Glendale/LA EPCU

Glendale, California, 91206, United States

Location

PAREXEL Intl - EPCU-Baltimore

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Overweight; Obesity; Diabetes Mellitus, Type 2

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Central Study Contacts

Novo Nordisk

CONTACT

(+1) 866-867-7178; clinicaltrials@novonordisk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2026
• First Posted: October 9, 2026
• Study Start: October 8, 2026
• Primary Completion (Estimated): September 7, 2028
• Study Completion (Estimated): September 7, 2028
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2)