A Trial to Investigate the Single Dose Pharmacokinetics of Insulin Degludec/Liraglutide Compared With Insulin Degludec and Liraglutide in Healthy Chinese Subjects

A Single Centre, Randomised, Double-blind, Three-period Cross-over Trial to Investigate the Single Dose Pharmacokinetics of Insulin Degludec/Liraglutide Compared With Insulin Degludec and Liraglutide in Healthy Chinese Subjects

The main purpose of the trial is to compare the bioavailability (extent of drug absorption into the circulation) of insulin degludec and liraglutide as part of a combination product insulin degludec/liraglutide compared to the corresponding doses of single, separate injections of insulin degludec and liraglutide. Participants will receive all three test substances. The order of trial administration will be allocated by chance. During the trial period, serials of blood samples will be collected from the participants at three dosing periods, in order to determine the concentration of insulin degludec and liraglutide. The total volume of blood taken throughout the whole trial period will be less than 400 mL. Participants will be asked to stay on daytime and overnight in the trial sites on some predefined days. For other outpatient days, participants need to attend the trial site as required for drug administration or required assessments.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin degludec/liraglutide; Drug: insulin degludec; Drug: liraglutide

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Male and female Chinese subjects, who are considered to be generally healthy, based on assessment of medical history, physical examination, and clinical laboratory data, as judged by the investigator
• Age between 18 to 45 years (both inclusive) at the time of signing informed consent
• Body mass index (BMI) between 19.0 and 24.0 kg/sqm (both inclusive)
• Body weight at least 50.0 kg
• Fasting plasma glucose less than 6.1 mmol/L (110 mg/dL)

Exclusion criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential not using an adequate contraceptive methods throughout the trial including follow-up period. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or barrier methods
• Donation of any blood or plasma in the past month or in excess of 400 mL within the 90 days preceding screening or surgery or trauma with more than 400 mL blood loss within the 90 days preceding screening
• History or presence of cancer, or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrine (incl. diabetes and recurrent hypoglycaemia), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders that might have impact on the trial result, as judged by the investigator
• Use of any prescription or non-prescription medication, except for paracetamol, acetylsalicylic acid, contraceptives and vitamins (mega-dose vitamin therapy not allowed, dose judged by the investigator) within 2 weeks prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IDeglira-IDeg-Liraglutide; Treatment sequence first Insulin Degludec/Liraglutide, then Insulin Degludec, then Liraglutide	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh
EXPERIMENTAL: IDeglira-Liraglutide-IDeg; Treatment sequence first Insulin Degludec/Liraglutide, then Liraglutide, then Insulin Degludec	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh
EXPERIMENTAL: IDeg-Liraglutide-IDeglira; Treatment sequence first Isulin Degludec, then Liraglutide, then Insulin Degludec/Liraglutide	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh
EXPERIMENTAL: IDeg-IDeglira-Liraglutide; Treatment sequence first Insulin Degludec, then Insulin Degludec/Liraglutide, then Liraglutide	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh
EXPERIMENTAL: Liraglutide-IDeg-IDeglira; Treatment sequence first Liraglutide, then Insulin Degludec, then Insulin Degludec/Liraglutide	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh
EXPERIMENTAL: Liraglutide-IDeglira-IDeg; Treatment sequence first Liraglutide, then Insulin Degludec/Liraglutide, then Insulin Degludec	Drug: insulin degludec/liraglutide; Insulin Degludec/Liraglutide combination product with 0.61 mg Liraglutide and 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: insulin degludec; 17 U Insulin Degludec, single dose administration under the skin in the thigh.; Drug: liraglutide; 0.6 mg Liraglutide, single dose administration under the skin in the thigh

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum insulin degludec concentration time curve	Calculated based on insulin degludec concentration in serum	From 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and insulin degludec, assessments from 0 hours to 120 hours
Area under the plasma liraglutide concentration time curve	Calculated based on liraglutide concentration in plasma	from 0 to last quantifiable observation after single dose of insulin degludec/liraglutide and liraglutide, assessments from 0 hours to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum insulin degludec concentration time curve from 0 to infinity after single dose	Calculated based on insulin degludec measured in serum	0 hours to 120 hours
Maximum observed serum insulin degludec concentration	Calculated based on insulin degludec measured in serum	0 hours to 120 hours
Time to maximum serum insulin degludec concentration	Calculated based on insulin degludec measured in serum	0 hours to 120 hours
Terminal elimination half-life for insulin degludec	Calculated based on insulin degludec measured in serum	0 hours to 120 hours
Area under the plasma liraglutide concentration time curve from 0 to infinity after single dose	Calculated based on liraglutide measured in plasma	0 hours to 72 hours
Maximum observed plasma liraglutide concentration	Calculated based on liraglutide measured in plasma	0 hours to 72 hours
Time to maximum plasma liraglutide concentration	Calculated based on liraglutide measured in plasma	0 hours to 72 hours
Terminal elimination half-life of liraglutide	Calculated based on liraglutide measured in plasma	0 hours to 72 hours
Number of treatment emergent adverse events	Count	Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)
Number of treatment emergent hypoglycaemic episodes	Count	Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)
Local tolerability at the injection site	Count	Visit 2 (Day 1, randomisation), Visit 5 (7-14 days after last dosing visit)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 29, 2017
• Primary Completion (ACTUAL): January 2, 2018
• Study Completion (ACTUAL): January 2, 2018

Study Registration Dates

• First Submitted: September 19, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (ACTUAL): September 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

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; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Liraglutide; Xultophy
• Other Study ID Numbers: NN9068-4139; U1111-1155-0990 (OTHER: World Health Organization (WHO))

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