A Study on How CagriSema Affects Levels of Atorvastatin and Warfarin in the Blood of Participants With Excess Body Weight

An Open-label, One-sequence Cross-over, Single-centre Trial, Investigating the Influence of CagriSema on Pharmacokinetics and Pharmacodynamics of Warfarin and Pharmacokinetics of Atorvastatin in Participants With Overweight or Obesity

This study will look at how CagriSema affects the blood levels of atorvastatin and warfarin. The study will look at the levels of warfarin and atorvastatin in the blood before the participant starts taking CagriSema and if this changes after the participant has taken CagriSema. The study will also investigate the effect of warfarin before and after the participant takes CagriSema and assess if the injection site affects the level of CagriSema in the blood. The study will last for about 8 months.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Semaglutide; Drug: Cagrilintide; Drug: Atorvastatin; Drug: Warfarin

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

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3P 3P1
      • Altasciences Company Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female.
• Aged 18-65 years (both inclusive) at the time of signing informed consent.
• Body Mass Index (BMI) between 27.0 and 39.9 kilograms per square meter (kg/m^2) (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator.

Exclusion Criteria:

• Previous dosing in a study with an amylin analogue.
• Presence or history of pathological bleeding tendencies, recent serious bleeding, recent myopathy or rhabdomyolysis, malignant hypertension and any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions including type 1 or type 2 diabetes mellitus.
• Presence of clinically significant gastrointestinal disorders or symptoms of gastrointestinal disorders potentially affecting absorption of drugs or nutrients, or as judged by the investigator.
• Glycated haemoglobin (HbA1c) greater than or equal to (≥) 6.5 % (48 millimoles per mole [mmol/mol]) at screening.
• Activated partial thromboplastin time (APTT) less than (<) 22.1 seconds (lower normal limit [LNL]-0%) or APTT greater than (>) 28.1 seconds (upper limit of normal [UNL) +0%) at screening.
• Prothrombin time < 70% (LNL-0%) or prothrombin time > 130% (UNL-0%) at screening.
• Use of prescription medicinal products or non-prescription drugs, including any herbal medicine known to interfere with the metabolic cytochrome P450 (CYP) pathways, such as perikon (St. John's Wort), ginseng, garlic, milk thistle, and echinaceae within 14 days (or within 5 half-lives of the medicinal product, whichever is longest) of screening, with the exception of use of routine vitamins (vitamins used within a normal dose reference interval), occasional use of paracetamol and highly effective contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CagriSema +Atorvastatin + Warfarin; Participants will receive a single dose of atorvastatin and a single dose of warfarin followed by a 16-week CagriSema dose escalation period and a 7-week CagriSema maintenance period. Participants will also receive a single dose of atorvastatin and a single dose of warfarin in the maintenance period.	Drug: Semaglutide; Semaglutide will be administered subcutaneously once weekly.; Drug: Cagrilintide; Cagrilintide will be administered subcutaneously once weekly.; Drug: Atorvastatin; Atorvastatin will be administered as a single dose orally 2 times during the study.; Drug: Warfarin; Warfarin will be administered as a single dose orally 2 times during the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-72hours,atorv,SD: Area under the atorvastatin plasma concentration-time curve from time 0 to 72 hours after a single dose of atorvastatin without CagriSema exposure and at CagriSema steady state	Measured in hours*nanomoles per liter (hours*nmol/L).	Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
AUC0-168hours,S-war,SD: Area under the S-warfarin plasma concentration-time curve from time 0 to 168 hours after a single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in hours*nmol/L.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-∞,atorv,SD: Area under the atorvastatin plasma concentration curve from time 0 to infinity after single dose of atorvastatin without CagriSema exposure and at CagriSema steady state	Measured in hours*nmol/L.	Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
Cmax,atorv,SD: Maximum observed atorvastatin plasma concentration after single dose of atorvastatin without CagriSema exposure and at CagriSema steady state	Measured in nanomoles per liter (nmol/L).	Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
tmax,atorv,SD: Time to maximum observed atorvastatin plasma concentration after single dose of atorvastatin without CagriSema exposure and at CagriSema steady state	Measured in hours.	Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
AUC0-∞,S-war,SD: Area under the S-warfarin plasma concentration curve from time 0 to infinity after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in hours*nmol/L.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
Cmax,S-war,SD: Maximum observed S-warfarin plasma concentration after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in nmol/L.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
tmax,S-war,SD: Time to maximum observed S-warfarin plasma concentration after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in hours.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
iAUCINR,0-168hours: Incremental area under the INR-curve from 0 to 168 hours after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in hours*nmol/L.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
INRmax: Maximum observed INR response after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in ratio.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
tINRmax: Time to maximum observed INR response after single dose of warfarin without CagriSema exposure and at CagriSema steady state	Measured in hours.	Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
AUC0-168hours,4th dose Sema: Area under the semaglutide plasma concentration curve from 0 to 168 hours after 4th dose of CagriSema	Measured in hours*nmol/L.	Day 44 (pre-dose to 168 hours post-dose)
Rac,0-168hours,cagri: The ratio of the area under the cagrilintide plasma concentration curve from 0 to 168 hours after the 4th dose of CagriSema to the area under the plasma concentration curve from 0 to 168 hours after the 1st dose	Measured in ratio.	Day 23 (pre-dose to 168 hours post-dose) and day 44 (pre-dose to 168 hours post-dose)
Rac,0-168hours,sema: The ratio of the area under the semaglutide plasma concentration curve from 0 to 168 hours after the 4th dose of CagriSema to the area under the plasma concentration curve from 0 to 168 hours after the 1st dose	Measured in ratio.	Day 23 (pre-dose to 168 hours post-dose) and day 44 (pre-dose to 168 hours post-dose
AUC0-168hours, 4th dose cagri: Area under the cagrilintide plasma concentration curve from 0 to 168 hours after 4th dose of CagriSema	Measured in hours*nmol/L.	Day 44 (pre-dose to 168 hours post-dose)
AUC0-168hours, cagri 2.4mg, SS: Area under the cagrilintide plasma concentration curve from 0 to 168 hours at steady state	Measured in hours*nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
AUC0-168hours, sema 2.4mg, SS: Area under the semaglutide plasma concentration curve from 0 to 168 hours at steady state	Measured in hours*nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
Cmax, cagri, SS: Maximum observed cagrilintide plasma concentration at steady state	Measured in nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
tmax, cagri, SS: Time to maximum observed cagrilintide plasma concentration at steady state	Measured in hours.	Day 163 (pre-dose to 168 hours post-dose)
Cmax, sema,SS: Maximum observed semaglutide plasma concentration at steady state	Measured in nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
tmax, sema, SS: Time to maximum observed semaglutide plasma concentration at steady state	Measured in hours.	Day 163 (pre-dose to 168 hours post-dose)
CL/Fcagri,SS: total apparent clearance of cagrilintide at steady state	Measured in litres per hour (L/h).	Day 163 (pre-dose to 168 hours post-dose)
CL/Fsema,SS: total apparent clearance of semaglutide at steady state	Measured in litres per hour (L/h).	Day 163 (pre-dose to 168 hours post-dose)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Actual): October 16, 2024
• Study Completion (Actual): November 15, 2024

Study Registration Dates

• First Submitted: February 25, 2024
• First Submitted That Met QC Criteria: February 25, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Fatty Acids; Lipids; Azoles; Pyrroles; Heptanoic Acids; Coumarins; Benzopyrans; 4-Hydroxycoumarins; Atorvastatin; Warfarin; semaglutide; cagrilintide
• Other Study ID Numbers: NN9838-4694; U1111-1295-4056 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No