Investigating the Pharmacokinetics, Safety and Tolerability After a Single Subcutaneous Injection of Semaglutide in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function

A Multi-centre, Open-label, Parallel-group Trial Investigating the Pharmacokinetics, Safety and Tolerability After a Single Subcutaneous Injection of Semaglutide in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Subjects With Normal Hepatic Function

This trial is conducted in Europe. The aim of this trial is to investigate the pharmacokinetics (the exposure of the trial drug in the body), safety and tolerability after a single injection of semaglutide in subjects with mild, moderate or severe hepatic impairment compared to subjects with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes; Hepatic Impaired
• Intervention / Treatment: Drug: semaglutide

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Warszawa, Poland, 02-507
    • Novo Nordisk Investigational Site
  • Wolomin, Poland, 05-200
    • Novo Nordisk Investigational Site
• Slovakia
  • Bratislava, Slovakia, 83101
    • Novo Nordisk Investigational Site
  • Bratislava, Slovakia, 833 05
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, age at least 18 years at the time of signing informed consent
• Body mass index (BMI) 18.5-40.0 kg/m^2 (both inclusive)
• Only for subjects with hepatic impairment (mild, moderate and severe): A diagnosis of cirrhosis due to parenchymal liver disease, classified as Child-Pugh grade A,B or C as assessed by investigator and which is confirmed and documented by medical history, physical examination and at least one of the following: hepatic ultrasound,computerised axial tomography (CT) scan, magnetic resonance imaging (MRI), and/or liver biopsy
• Only for subjects with normal hepatic function: Subjects who are judged to be in good general health based on physical examination, medical history, ECG, vital signs, and the results of biochemistry, coagulation, haematology tests and urinalysis performed during the screening visit, as judged by the investigator

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential not using an adequate contraceptive method throughout the trial including the follow-up period (adequate contraceptive measures as required by local regulation or practice)
• Uncontrolled hypertension (defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 100 mmHg). If white-coat hypertension is suspected at the screening visit a repeated measurement at the screening visit is allowed
• Mental inability, unwillingness or language barrier precluding adequate understanding of or compliance with trial procedures
• Donation of any blood or plasma in the past month or in excess of 400 mL within the 3 months preceding screening, or surgery or trauma with more than 400 mL blood loss within the 3 months preceding screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal hepatic function	Drug: semaglutide; All subjects will be treated with a single subcutane (s.c., under the skin) injection of 0.5 mg semaglutide.
Experimental: Mild hepatic impairment	Drug: semaglutide; All subjects will be treated with a single subcutane (s.c., under the skin) injection of 0.5 mg semaglutide.
Experimental: Moderate hepatic impairment	Drug: semaglutide; All subjects will be treated with a single subcutane (s.c., under the skin) injection of 0.5 mg semaglutide.
Experimental: Severe hepatic impairment	Drug: semaglutide; All subjects will be treated with a single subcutane (s.c., under the skin) injection of 0.5 mg semaglutide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the semaglutide plasma concentration-time curve	Day 1 - day 36

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed semaglutide plasma concentration	Day 1 - day 36
Number of treatment emergent adverse events (TEAEs)	Day 1 - day 36

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry GCR, 1452, Novo Nordisk A/S

Publications and helpful links

General Publications

• Jensen L, Kupcova V, Arold G, Pettersson J, Hjerpsted JB. Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment. Diabetes Obes Metab. 2018 Apr;20(4):998-1005. doi: 10.1111/dom.13186. Epub 2018 Jan 17.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2014
• Primary Completion (Actual): June 3, 2015
• Study Completion (Actual): June 3, 2015

Study Registration Dates

• First Submitted: August 6, 2014
• First Submitted That Met QC Criteria: August 6, 2014
• First Posted (Estimate): August 7, 2014

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN9535-3651; U1111-1149-3924 (Other Identifier: WHO); 2009-011673-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No