A Study to Test Whether BI 456906 (Survodutide) Influences the Amount of Bupropion, Caffeine and Midazolam in the Blood in People With Overweight or Obesity

An Open-label, Non-randomised, Fixed-sequence, Two Period, Phase I Trial to Evaluate the Effect of Different Doses of BI 456906 (Survodutide) on the Single Dose Pharmacokinetics of Bupropion, Caffeine and Midazolam on Otherwise Healthy Volunteers With Overweight or Obesity

This study is open to adults with overweight or obesity who are otherwise healthy. People can join the study if they have a body mass index of 27 to 39.9 kg/m2 and a body weight over 70 kg. The purpose of this study is to find out whether taking multiple doses of BI 456906 influences the amount of bupropion, caffeine, and midazolam in the blood.

The study has 2 treatment periods. In Period 1, participants take 1 dose each of midazolam, caffeine, and bupropion as tablets or oral solution on separate days. In Period 2, participants get BI 456906 as an injection under the skin once a week. At 2 selected timepoints in Period 2, participants also take midazolam, caffeine and bupropion as tablets or oral solution on separate days.

Participants are in the study for about 13 months. They visit the study site up to 45 times. At 3 of those visits, participants stay for 5 or 6 days at the study site. During the visits, doctors collect information about participants' health and take blood samples from the participants. They compare the amounts of midazolam, caffeine, and bupropion in the blood in Period 2 with the amounts in Period 1. Doctors also regularly check participants' health and take note of any unwanted effects.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Bupropion; Drug: Midazolam; Drug: Caffeine; Combination product: Survodutide

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • SGS Life Science Services - Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria :

1. Otherwise healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
2. Age of 18 to 60 years (inclusive) at signing of informed consent
3. Body mass index (BMI) of 27.0 to 39.9 kg/m² (inclusive) and body weight > 70 kg
4. Signed and dated written informed consent in accordance with International Council for Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial, i.e. prior to starting any screening procedures legislation prior to admission to the trial, i.e. prior to starting any screening procedures
5. Further inclusion criteria apply

Exclusion Criteria :

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator.
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)

3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance and in particular:

   • Alanine aminotransferase (ALT) above upper limit of normal (ULN) + 20%,
   • Aspartate aminotransferase (AST) above ULN + 20%,
   • Gamma-Glutamyl-Transferase (GGT) above ULN + 20%,
   • Lipase or amylase above ULN + 20%,
   • Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m².
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: All participants; In Period 1: Bupropion, Caffeine, Midazolam are given as a reference treatment. In Period 2: Survodutide, Bupropion, Caffeine, Midazolam are given as a test treatment.	Drug: Bupropion; Bupropion; Other Names: Wellbutrin® XR; Drug: Midazolam; Midazolam; Other Names: Midazolam Accord®; Drug: Caffeine; Caffeine; Other Names: Coffeinum® N; Combination product: Survodutide; Survodutide, pre-filled syringe; Other Names: BI 456906

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of bupropion in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞)	Up to week 32
Area under the concentration-time curve of the caffeine in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞)	Up to week 32
Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞)	Up to week 32
Maximum measured concentration of bupropion in plasma (Cmax)	Up to week 32
Maximum measured concentration of caffeine in plasma (Cmax)	Up to week 32
Maximum measured concentration of midazolam in plasma (Cmax)	Up to week 32

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): December 16, 2025
• Study Completion (Actual): January 5, 2026

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Benzazepines; Benzodiazepines; Ketones; Xanthines; Propiophenones; Midazolam; Caffeine; Bupropion; BI 456906
• Other Study ID Numbers: 1404-0008; 2024-512332-29-00 (Registry Identifier: CTIS (EU)); U1111-1307-0132 (Registry Identifier: WHO International Clinical Trials Registry Platform (ICTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes