Open, Randomized Crossover Study on PK, PD, Biopotency, and Bioavailability of Insulin Capsules in Healthy Chinese Males

An Open, Randomized, Single Dose (32mg), Two-way Crossover Study on Pharmacokinetics, Pharmacodynamics, Relative Biopotency and Bioavailability of Human Insulin Enteric Coated Capsules in Healthy Chinese Male Subjects

Pharmacokinetics and pharmacodynamics study of 2 formulations (human insulin enteric coated capsules 32mg vs. human insulin injection 5IU) Relative biopotency and bioavailability of human insulin enteric coated capsules 32mg vs. human insulin injection 5IU

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Human insulin enteric coated capsules in dose 32mg; Drug: Human Insulin Injection in dose 5IU

Detailed Description

An open, randomized, single dose, two-way crossover study on Pharmacokinetics, pharmacodynamics, relative biopotency and bioavailability of human insulin enteric coated capsules in healthy Chinese male subjects using hyperinsulinemic-euglycemic clamp.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yifei Zhang, MD, PHD; Phone Number: +86-13524640378; Email: feifei-a@163.com
• Study Contact Backup: Name: Weiqing Wang, MD, PHD; Phone Number: +86-64370045; Email: wqingw@shsmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy Chinese male subjects aged 20-35 (inclusive);
2. Body mass index (BMI) between 19 and 24 kg/m2 ( extrems inclusive, body mass index= body weight/ height2);
3. Normal oral glucose tolerance Test (fasting plasma glucose [FPG]< 6.1 mmol/L and 2-hour postprandial blood glucose after loading with glucose [2hPG]< 7.8 mmol/L), and HbA1C<6.0%
4. Normal insulin releasing test (judged by investigator);
5. Considered generally healthy upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, without history of acute and chronic diseases with clinical significance, incl.: of the cardiovascular system, bronchopulmonary, neuroendocrine systems, endocrine system, as well as diseases of the gastrointestinal tract, liver, kidneys, blood, as judged by the Investigator.
6. Signed informed consent and volunteers' consent to all restrictions imposed during the study.

Exclusion Criteria:

1. Known allergic or suspected hypersensitivity to investigational product (IP) or related product
2. Previous or existing diseases of the cardiovascular system, endocrine system, gastrointestinal system, nervous system, or diseases of the lungs, hematologic, immunology, psychiatry, and metabolic abnormalities, as judged by the investigator;
3. History of heavy smoking, alcohol abuse, and drug abuse;
4. Taking more than 14 units alcohol per week within 3 months prior to screening (1unit≈360 mL of beer, 45mL of spirits, or 150 mL of wine), or receiving alcohol within 48 hours prior to IP administration, or failure to abstain from alcohol during the trial;
5. Receiving excessive amounts of tea, coffee, and/or caffeine rich beverages (8 or more cups, 1 cup ≈ 250 mL) per day within 3 months prior to screening;
6. Use of any medication that may affect glucose lowering effect (such as oral contraceptives, corticosteroids, diuretics, adrenaline, salbutamol, glucagon, growth hormone, thyroid hormone, etc.) within 28 days prior to screening;
7. Taking any medications, vitamin products, or any Chinese herbal medicine or nutrition supplements within 2 weeks prior to IP administration;
8. Participation in any clinical trial less than 3 months prior to screening or planning to participate in other trials after ICF signed.
9. Blood donation or blood loss≥ 200mL of any reasons within 3 months prior to screening; history of blood transfusion or component blood transfusion; failure to guarantee not to donate whole blood / component blood (such as plasma, platelets) during the trial or within 30 days after the end of the trial;
10. Undergo surgery prior to IP administration within 1month or plan to undergo surgery during the trial;
11. Occurrence of acute disease during screening;
12. Positive test of any: HIV-Ab, HBSAg, HCV-Ab,TP-Ab;
13. History of needle phobia and blood phobia;
14. Any conditions that make volunteer participation ineligible judged by investigating physician.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human insulin enteric coated capsules in dose 32mg; Single oral administration of human insulin enteric coated capsules in dose 32mg.	Drug: Human insulin enteric coated capsules in dose 32mg; Single oral administration of human insulin enteric coated capsules in dose 32mg (16 mg per capsule, two capsules).
Active Comparator: Human Insulin Injection in dose 5 IU; Single subcutaneous administration of Human Insulin Injection in dose 5IU.	Drug: Human Insulin Injection in dose 5IU; Single subcutaneous administration of Human Insulin Injection in dose 5IU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GIRmax	PD endpoint: The maximum glucose infusion rate	0-11 hours (hyperinsulinemic-euglycemic clamp)
TGIRmax	PD endpoint: The time to maximum observed glucose infusion rate	0-11 hours (hyperinsulinemic-euglycemic clamp)
AUCGIR 0-11h	PD endpoint: The area under the glucose infusion rate curve from 0 to 11 hours	0-11 hours (hyperinsulinemic-euglycemic clamp)
AUCGIR0-∞	PD endpoint: The area under the glucose infusion rate curve from 0 to infinity	0-11 hours (hyperinsulinemic-euglycemic clamp)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	PK endpoint: The maximum observed insulin concentration	0-11 hours (hyperinsulinemic-euglycemic clamp)
Tmax	PK endpoint: The time to maximum observed insulin concentration	0-11 hours (hyperinsulinemic-euglycemic clamp)
AUCIns0-∞	PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity	0-11 hours (hyperinsulinemic-euglycemic clamp)
AUCIns0-11h	PK endpoint: The area under the insulin concentration curve from 0 to 11 hours	0-11 hours (hyperinsulinemic-euglycemic clamp)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative biopotency	(AUCGIR of capsule:dosage)/(AUCGIR of injection:dosage)	0-11 hours (hyperinsulinemic-euglycemic clamp)
Relative bioavailability	(AUCins of capsule:dosage)/(AUCins of injection:dosage)	0-11 hours (hyperinsulinemic-euglycemic clamp)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Number of participants experiencing treatment-emergent adverse events	Up to Day 14

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2025
• Primary Completion (Estimated): April 24, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hypoglycemic Agents; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: ORA-H-CN-008

Drug and device information, study documents

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