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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin degludec/liraglutide
* Drug: insulin degludec
* Drug: liraglutide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Three-period complete cross-over, six treatment sequences
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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) |