A Clinical Study Comparing the Pharmacokinetics and Pharmacodynamic Characteristics of Insulin Degludec Injection (RD15003) and Insulin Degludec Injection (Tresiba®) in Healthy Subjects

Pharmacokinetics, Pharmacodynamic, Safety and Immunogenicity Characteristics of Insulin Degludec Injection (RD15003) and Insulin Degludec Injection ( Tresiba®）in Healthy Subjects: a Phase I Single-center, Randomized, Open-label, Single-dose, Cross-over Clinical Study

To evaluate the single-dose subcutaneous injection of insulin degludec injection (Tresiba®) listed by Novo Nordisk in China as a reference drug, the insulin degludec injection provided by Dongguan Dongyang Sunshine Biopharmaceutical R&D Co., Ltd. (RD15003) pharmacokinetics and pharmacodynamic characteristics in healthy subjects, and then to evaluate the bioequivalence of test drugs and control drugs.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Biological: Insulin degludec injection, RD15003; Biological: Insulin degludec, Tresiba

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Volunteer to participate in the trial, and sign the informed consent form, and be able to complete the trial in accordance with the requirements of the plan;
2. When signing the informed consent form, healthy subjects aged 18-45 (including the cut-off value) are not limited to males and females;
3. At the time of screening, male weight > or = 50 kg, female weight > or = 45 kg, body mass index (BMI) > or = 19.0 and < or = 26.0 kg/m2;
4. After medical history inquiry, there is no clinically significant heart, liver, kidney, digestive tract, nervous system disease, and metabolic abnormality history;
5. Vital signs, physical examination, laboratory examination and/or ECG, chest X-ray examination results are normal or abnormal, but the investigator judges that they have no clinical significance;
6. Normal glucose tolerance [fasting blood glucose (FPG) <6.1 mmol/L, and oral glucose tolerance test (OGTT) 2 h postprandial blood glucose <7.8 mmol/L];
7. Insulin release test (IRT) results are normal or abnormal, but the investigator judges that it has no clinical significance;
8. Have good venous conditions, so that blood collection channels can be established according to the research plan;
9. There was no birth plan during the study period and promised to use reliable contraceptive measures throughout the study period until 4 weeks after the last administration of the trial drug.

Exclusion Criteria:

1. Have a history of hypoglycemia within 3 months before screening;
2. Those who have taken any prescription drugs, Chinese herbal medicines, over-the-counter drugs (except for subjects with occasional and restricted use of paracetamol), and health care products (except routine supplementary vitamins and calcium) within 4 weeks before administration;
3. During screening, the test results of human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or Treponema pallidum antibody were positive;
4. Have a history of malignant tumors before screening;
5. Participated in any drug or device clinical research within 3 months before screening (the definition of participation: refers to random or receiving experimental drugs or devices);
6. Blood donation > or = 400 mL within 3 months before administration, or blood loss > or = 400 mL due to any reason;
7. People who are known to be allergic to the test drug or its excipients;
8. People who drink regularly within 3 months before administration, that is, drink more than 21 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% alcoholic spirits or 150 mL of wine), or those who have a positive alcohol breath test ;
9. Those who have a positive urine drug screening;
10. Positive anti-insulin antibody during the screening period;
11. Female subjects who are breastfeeding, or women who have a positive blood pregnancy test during the screening period;
12. Those who smoked more than 10 cigarettes per day within 3 months before the administration, or failed to comply with the ban on smoking during the trial period;
13. There are any factors considered by the researcher to be unsuitable for participating in the research;
14. If during the period of new coronary pneumonia, the investigator decided to conduct relevant tests for the new coronavirus according to the requirements of the Sichuan Provincial Health Commission and West China Hospital of Sichuan University at the time of the trial, and the abnormal results have clinical significance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TR sequence; Experimental:Insulin degludec injection (RD15003)+Tresiba Subjects receive Insulin degludec injection(RD15003) in the first cycle and Tresiba in the second cycle.	Biological: Insulin degludec injection, RD15003; single dose, s.c. injection; Biological: Insulin degludec, Tresiba; single dose, s.c. injection
EXPERIMENTAL: RT sequence; Experimental:Tresiba+Insulin degludec injection (RD15003) Subjects receive Insulin Tresiba in the first cycle and degludec injection(RD15003) in the second cycle.	Biological: Insulin degludec injection, RD15003; single dose, s.c. injection; Biological: Insulin degludec, Tresiba; single dose, s.c. injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from time zero to 24 hours	AUC0-24h	24 hours after injection
Area under the glucose infusion rate curve from administration to end of clamp from time zero to 24 hours	GIR-AUC0-24h	24 hours after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from time zero to 12 hours	AUC0-12h	12 hours after injection
Area under the glucose infusion rate curve from administration to end of clamp from time zero to 12 hours	AUCGIR0-12h	12 hours after injection
Safety evaluation	Incidence of adverse events	Up to 24 weeks
Area under the plasma concentration-time curve from time 12 hours to 24 hours	AUC12-24h	12-24 hours after injection
Area under the plasma concentration-time curve from time zero to t	AUC0-t	120 hours after injection
Area under the glucose infusion rate curve from administration to end of clamp from time 12 hours to 24 hours	AUCGIR, 12-24h	12-24 hours after injection
Maximum glucose infusion rate	GIRmax	24 hours after injection

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 8, 2021
• Primary Completion (ACTUAL): March 21, 2022
• Study Completion (ACTUAL): March 21, 2022

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (ACTUAL): October 12, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting
• Other Study ID Numbers: RD15003-P-01

Drug and device information, study documents

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