First Human Dose Trial for a New Medication to Potentially Treat Liver Diseases

A First Human Dose Study Investigating Safety, Tolerability, and Pharmacokinetics of Single Subcutaneous Injections of NNC0581-0001 in Healthy Adults and in Participants With Hepatic Steatosis

This study will assess the safety, tolerability, the pharmacokinetics from single injection (under the skin) of NNC0581-0001 and explores the pharmacodynamics in healthy participants and participants with hepatic steatosis (increased liver fat). Participants will either get NNC0581-001 or Placebo (dummy treatment). Which treatment participants get is decided by chance.NNC0581-0001 is a new medicine which cannot be prescribed by doctors. The study will last about 58 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Steatosis
• Intervention / Treatment: Drug: NNC0581-0001; Drug: Placebo (NNC0581-0001)

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Parexel CPRU, Level 7
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Parexel Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria, for healthy participants in Part A:

• Female of non-childbearing potential or male aged 18-55 years (both inclusive) at the time of signing informed consent.
• Body Mass Index (BMI) from 18.5 to 30.0 kilogram per square meter (kg/m^2) (both inclusive) at screening.
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram, and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Inclusion criteria for participants with hepatic steatosis in Part B:

• Female of non-childbearing potential or male aged 18-55 years (both inclusive) at the time of signing informed consent.
• Body Mass Index (BMI) from 25.0 to 34.9 kilogram per square meter (kg/m^2) (both inclusive) at screening.
• Hepatic steatosis identified by a score above 248 dB/m by Fibroscan® (Controlled Attenuated Parameter, CAP) at screening.

Exclusion Criteria

• Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• For Part A: Any laboratory safety parameters at screening outside the below laboratory ranges, see laboratory provided reference ranges for specific values (re-screening or re-sampling is NOT allowed if the participant has failed one of the exclusion criteria related to laboratory parameters):
• Alanine aminotransferase (ALT) greater than upper normal limit (UNL) plus 10 percent
• Aspartate aminotransferase (AST) greater than UNL plus 10 percent
• Bilirubin greater than UNL plus 10 percent
• Estimated glomerular filtration rate (eGFR) below 90 milliliters per minute per 1.73 square meters (90 mL/min/1.73m^2)
• Glycated haemoglobin (HbA1c) greater than or equal to 5.7 percent (39 millimole per mole [mmol/mol]) at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Dose 1: NNC0581-0001 10 milligram (mg); Part A: Healthy participants will receive a single dose of NNC0581-0001 10 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.
Experimental: Single Dose 2: NNC0581-0001 30 mg; Part A: Healthy participants will receive a single dose of NNC0581-0001 30 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.
Experimental: Single Dose 3: NNC0581-0001 90 mg; Part A: Healthy participants will receive a single dose of NNC0581-0001 90 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.
Experimental: Single Dose 4: NNC0581-0001 250 mg; Part A: Healthy participants will receive a single dose of NNC0581-0001 250 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.
Experimental: Single Dose 5: NNC0581-001 600 mg; Part B: Participants with hepatic steatosis will receive a single dose of NNC0581-0001 600 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.
Experimental: Single Dose 6: NNC0581-001 1000 mg; Part B: Participants with hepatic steatosis will receive a single dose of NNC0581-0001 1000 mg or matching placebo injection subcutaneously.	Drug: NNC0581-0001; Participants will receive up to six single dose levels of subcutaneous NNC0581-0001 in a sequential manner with the dose increasing between cohorts.; Drug: Placebo (NNC0581-0001); Participants will receive single dose of subcutaneous injection of placebo matched to NNC0581-0001.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment emergent adverse events (TEAEs)	Measured as number of events.	From dosing (Day 1) until completion of the End of Study Visit at week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-∞: The area under the NNC0581-0001 plasma concentration-time curve from time zero to infinity after a single dose	Measured in nanogram hour per mililiter (ng*h/mL).	From dosing (Day 1) to 168 hours after dosing
Cmax: The maximum concentration of NNC0581-0001 in plasma after a single dose	Measured in nanogram per mililiter (ng/mL).	From dosing (Day 1) to 168 hours after dosing
tmax: The time from dose administration to maximum plasma concentration of NNC0581-0001 after a single dose	Measured in Hours.	From dosing (Day 1) to 168 hours after dosing

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): November 23, 2022
• Primary Completion (Actual): August 29, 2025
• Study Completion (Actual): August 29, 2025

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: NN6581-4860; U1111-1274-4577 (Other Identifier: World Health Organization (WHO)); 2022-001359-18 (EudraCT Number)

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