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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06289504
• Other study ID #: NN9838-4694
• Secondary ID: U1111-1295-4056
• Status: Recruiting
• Phase: Phase 1
• Start date: February 27, 2024
• Est. completion date: November 16, 2024

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 16, 2024
• Est. primary completion date: November 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Cagrilintide
Cagrilintide will be administered subcutaneously once weekly.
• Semaglutide
Semaglutide will be administered subcutaneously once weekly.
• Atorvastatin
Atorvastatin will be administered as a single dose orally 2 times during the study.
• Warfarin
Warfarin will be administered as a single dose orally 2 times during the study.

Locations

Country	Name	City	State
Canada	Altasciences Company Inc.	Mount-Royal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	AUC0-8,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)
Secondary	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)
Secondary	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)
Secondary	AUC0-8,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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Cmax, cagri, SS: Maximum observed cagrilintide plasma concentration at steady state	Measured in nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
Secondary	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)
Secondary	Cmax, sema,SS: Maximum observed semaglutide plasma concentration at steady state	Measured in nmol/L.	Day 163 (pre-dose to 168 hours post-dose)
Secondary	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)
Secondary	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)
Secondary	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)