A Research Study to Compare Blood Levels of Cagrilintide and Semaglutide After Combined Versus Separate Injections in People With Overweight or Obesity

Study Overview
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Brief Summary
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This study will compare two different ways of giving cagrilintide and semaglutide for treating overweight and obesity. The medicines will either be given together in 1 injection or as 2 separate injections. The aim of the study is to find out how the different ways of injection affect the level of the medicines in the blood. For the first 14 weeks of the study, participants will get cagrilintide and semaglutide as 2 separate injections. Then participants will either switch to getting the medicines as a combined injection or continue to get the separate injections for 8 weeks. Which treatment participants get after the first 14 weeks is decided by chance. Participants will get the study medicines once a week for 22 weeks. A study nurse at the clinic will inject the medicines with a thin needle in participants stomach area. The study will last for about 8 months.Participants will have 28 clinic visits with the study staff. For 4 of these visits, participants will stay in the clinic for 5 nights. Participants will have blood drawn at 21 visits. Participants will have clinical assessments and participants will be asked about their health, medical history and habits including mental health questionnaires. For women: Participants must not be able to become pregnant if they wish to participate in this study.

Official Title
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Investigation of Pharmacokinetics Following Co-administration of Cagrilintide (NNC0174-0833) and Semaglutide Versus Separate Injections in Subjects With Overweight or Obesity

Conditions
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Obesity & Overweight

Intervention / Treatment
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* Drug: Cagrilintide
* Drug: semaglutide
* Drug: Cagrilintide and semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of non-childbearing potential (NCBP) Aged 18-55 years (both inclusive) at the time of signing informed consent Body mass index (BMI) between 27.0 and 39.9 kg/m^2 (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator Exclusion Criteria: Previous participation in trial(s) with an amylin analogue unless documented that the subject was assigned to placebo treatment. Participation is defined as randomisation Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial consists of a Part A with multiple weekly dosings at site and a Part B with a single dose (SD) part of the first dose step in Part A.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Cagrilintide and semaglutide in separate syringes<br>Participants will up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks treatment with cagrilintide and semaglutide administered as separate injections. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination). Followed by a 38 days follow-up period. | Drug: Cagrilintide<br>* Once weekly doses of cagrilintide gradually increased to 1.7 mg over 14 weeks and 2.4 mg s.c. for 2 weeks<br>Drug: semaglutide<br>* Once weekly doses of semaglutide gradually increased to 1.7 mg over 14 weeks and 2.4 mg s.c. over 2 weeks<br>|
| Experimental: Part A: Cagrilintide and semaglutide combined in DV3384 device<br>Participants will be up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks of treatment with cagrilintide and semaglutide administered using the DV3384 manual syringe. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination. Followed by a 38 days follow-up period. | Drug: Cagrilintide and semaglutide<br>* Cagrilintide and semaglutide combined and administered using the DV3384 manual syringe<br>|
| Experimental: Part B: Cagrilintide and semaglutide combined in DV3384 device<br>Participants will receive a single injection of Cagrilintide 0.25 mg/semaglutide 0.25 mg using the DV3384 manual syringe followed by a 28 days follow-up period. | Drug: Cagrilintide and semaglutide<br>* Cagrilintide and semaglutide combined and administered using the DV3384 manual syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-168h,cagri,2.4/2.4mg,SS area under the cagrilintide concentration-time curve during a dosing interval (0-168 hours) at steady state after last dosing of cagrilintide 2.4 mg in combination with semaglutide 2.4 mg | measured in nmol⸱h/L | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 
| Cmax,cagri,2.4/2.4mg,SS maximum concentration of cagrilintide at steady state after last dosing of cagrilintide 2.4 mg in combination with semaglutide 2.4 mg | measured in nmol/L | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 
| AUC0-168h,sema,2.4/2.4mg,SS area under the semaglutide concentration-time curve during a dosing interval (0-168 hours) at steady state after last dosing of semaglutide 2.4 mg in combination with cagrilintide 2.4 mg | measured in nmol⸱h/L | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 
| Cmax,sema,2.4/2.4mg,SS maximum concentration of semaglutide at steady state after last dosing of semaglutide 2.4 mg in combination with cagrilintide 2.4 mg | measured in nmol/L | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax,cagri,2.4/2.4mg,SS time since last dosing to maximum concentration of cagrilintide at steady state after last dosing of cagrilintide 2.4 mg in combination with semaglutide 2.4 mg | measured in hours | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 
| t½,cagri,2.4/2.4mg,SS terminal half-life of cagrilintide at steady state after last dosing of cagrilintide 2.4 mg in combination with semaglutide 2.4 mg | measured in hours | Day 148 (pre-dose) to Day 186 (912 hours post-dose) | 
| tmax,sema,2.4/2.4mg,SS time since last dosing to maximum concentration of semaglutide at steady state after last dosing of semaglutide 2.4 mg in combination with cagrilintide 2.4 mg | measured in hours | Day 148 (pre-dose) to Day 155 (168 hours post-dose) | 
| t½,sema,2.4/2.4mg,SS terminal half-life of semaglutide at steady state after last dosing of semaglutide 2.4 mg in combination with cagrilintide 2.4 mg | measured in hours | Day 148 (pre-dose) to Day 186 (912 hours post-dose) | 
| AUC0-168h,cagri,1.7/1.7mg,SS area under the cagrilintide concentration-time curve during a dosing interval (0-168 hours) at steady state after last dose of cagrilintide 1.7 mg in combination with semaglutide 1.7 mg | measured in nmol⸱h/L | Day 120 (pre-dose) to Day 127 (168 hours post-dose) | 
| AUC0-168h,sema,1.7/1.7mg,SS area under the semaglutide concentration-time curve during a dosing interval (0-168 hours) at steady state after last dose of semaglutide 1.7 mg in combination with cagrilintide 1.7 mg | measured in nmol⸱h/L | Day 120 (pre-dose) to Day 127 (168 hours post-dose) | 
| PART A: Number of treatment emergent adverse events | count | From time of dosing (Day 1) to follow-up (Day 186) | 
| PART B: Number of treatment emergent adverse events | Count | From time of dosing (Day 1) to follow-up (Day 29) |