Clinical trial NCT06289504: A Study on How CagriSema Affects Levels of Atorvastatin and Warfarin in the Blood of Participants With Excess Body Weight
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
measure: 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
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
Secondary outcomes:
measure: 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
timeFrame: Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
measure: Cmax,atorv,SD: Maximum observed atorvastatin plasma concentration after single dose of atorvastatin without CagriSema exposure and at CagriSema steady state
timeFrame: Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
measure: tmax,atorv,SD: Time to maximum observed atorvastatin plasma concentration after single dose of atorvastatin without CagriSema exposure and at CagriSema steady state
timeFrame: Day 1 (pre-dose to 72 hours post-dose) and day 171 (pre-dose to 72 hours post-dose)
measure: 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
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: Cmax,S-war,SD: Maximum observed S-warfarin plasma concentration after single dose of warfarin without CagriSema exposure and at CagriSema steady state
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: 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
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: 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
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: INRmax: Maximum observed INR response after single dose of warfarin without CagriSema exposure and at CagriSema steady state
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: tINRmax: Time to maximum observed INR response after single dose of warfarin without CagriSema exposure and at CagriSema steady state
timeFrame: Day 8 (pre-dose to 168 hours post-dose) and day 178 (pre-dose to 168 hours post-dose)
measure: 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
timeFrame: Day 23 (pre-dose to 168 hours post-dose) and day 44 (pre-dose to 168 hours post-dose)
measure: 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
timeFrame: Day 23 (pre-dose to 168 hours post-dose) and day 44 (pre-dose to 168 hours post-dose
measure: AUC0-168hours, 4th dose cagri: Area under the cagrilintide plasma concentration curve from 0 to 168 hours after 4th dose of CagriSema
timeFrame: Day 44 (pre-dose to 168 hours post-dose)
measure: AUC0-168hours,4th dose Sema: Area under the semaglutide plasma concentration curve from 0 to 168 hours after 4th dose of CagriSema
timeFrame: Day 44 (pre-dose to 168 hours post-dose)
measure: AUC0-168hours, cagri 2.4mg, SS: Area under the cagrilintide plasma concentration curve from 0 to 168 hours at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: AUC0-168hours, sema 2.4mg, SS: Area under the semaglutide plasma concentration curve from 0 to 168 hours at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: Cmax, cagri, SS: Maximum observed cagrilintide plasma concentration at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: tmax, cagri, SS: Time to maximum observed cagrilintide plasma concentration at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: Cmax, sema,SS: Maximum observed semaglutide plasma concentration at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: tmax, sema, SS: Time to maximum observed semaglutide plasma concentration at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: CL/Fcagri,SS: total apparent clearance of cagrilintide at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
measure: CL/Fsema,SS: total apparent clearance of semaglutide at steady state
timeFrame: Day 163 (pre-dose to 168 hours post-dose)
Other outcomes:
Locations:
city: Mount-Royal
country: Canada
facility: Altasciences Company Inc.
state: Quebec
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: