A Research Study Looking Into Blood and Urine Levels of the Medicine NNC0194-0499 in the Body and How Well it is Tolerated in Participants With Reduced Kidney Function and Normal Kidney Function

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

Investigation of Pharmacokinetics, Safety and Tolerability of a Single Subcutaneous Dose of NNC0194-0499 in Participants With Various Degrees of Renal Impairment and Normal Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05727644
• Other study ID #: NN9500-4620
• Secondary ID: U1111-1277-36462
• Status: Completed
• Phase: Phase 1
• Start date: February 15, 2023
• Est. completion date: November 10, 2023

Study information

• Verified date: December 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Novo Nordisk is developing the study medicine NNC0194-0499 for the treatment of non-alcoholic steatohepatitis (NASH). NASH is a serious disease where fat, inflammation and scar tissue builds up in the liver. In this study the blood and urine levels of NNC0194-0499 will be compared in people with various degrees of reduced kidney function to the blood and urine levels in people with normal kidney function, after administration of one dose of 30 milligrams (mg) NNC0194-0499. Participant will only get the study medicine in one injection into a skinfold in the thigh (subcutaneous). The study will last for about 66 days including a screening phase of up to 28 days prior to dosing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 10, 2023
• Est. primary completion date: November 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male or female, aged 18-80 years (both inclusive) at the time of signing informed consent.

• Body mass index (BMI) between 18.5-39.9 kilogram per meter square (kg/m2) (both inclusive).

• Meeting the pre-defined estimated glomerular filtration rate (eGFR) values based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation according to Kidney Disease: Improving Global Outcomes (KDIGO) 20121, 2 standardized to the individual body surface area (BSA).

Group description eGFR (mL/min)

1. Normal renal function greater than or equal to 90

2. Mild renal impairment 60 - 89

3. Moderate renal impairment 30 - 59

4. Severe renal impairment 15 - 29 not requiring dialysis

5. End-Stage Renal Disease (ESRD) less than 15 or requiring dialysis treatment Renal group 5 (ESRD).

• Participants requiring dialysis treatment should be on treatment with haemodialysis.

Exclusion Criteria:

• Any disorder, except for conditions associated with renal impairment, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.

• Use of prescription medicinal products or non-prescription drugs, or non-routine vitamins, which at the investigators judgement may affect participant safety or the results of the study within 14 days before screening. Use of the following are allowed: Routine vitamins, occasional use of paracetamol, ibuprofen and topical medication not reaching systemic circulation.

• Use of drugs known to affect creatinine clearance including cephalosporin and aminoglycoside antibiotics, flucytosine, cisplatin, cimetidine, trimethoprim, cibenzoline and nitrofurantoin within 14 days or 5 half-lives, whichever is greater, before planned dosing of the investigational medicinal product (IMP).

• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, or endocrinological conditions (except conditions associated with renal impairment or ESRD).

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• NNC0194-0499
Participants will receive a single subcutaneous injection of 30 mg NNC0194-0499.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC0499,0-8,SD: Area under the NNC0194-0499 serum concentration-time curve after a single dose	Measured as hours*nanomoles per litre (h*nmol/L)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	Cmax,0499,SD: Maximum observed serum NNC0194-0499 concentration after a single dose	Measured as nanomoles per litre (nmol/L)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	tmax,0499,SD: Time to maximum observed serum NNC0194-0499 concentration after a single dose	Measured in hours (h)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	t½,0499,SD: Terminal half-life of NNC0194-0499 after a single dose	Measured in hours (h)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	Vz/F0499,SD: Apparent volume of distribution of NNC0194-0499 after a single dose	Measured as Litre (L)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	CL/F0499,SD: Apparent clearance of NNC0194-0499 after a single dose	Measured as Litre per hour (L/h)	From baseline (Visit 2, Day 1, pre-dose) until completion of the end of study visit (Visit 9, Day 36)
Secondary	CLR,0499,SD: Renal clearance of NNC0194-0499 after a single dose	Measured as Litre per hour (L/h)	From baseline (Visit 2, Day 1, predose) until completion of the urine collection period 96 hours after dosing (Visit 2, Day 5)