A Study Evaluating Drug-Drug Interaction (DDI) Between HSK16149 Capsules and Metformin Hydrochloride Tablets

Phase I Clinical Study to Evaluate the Drug-drug Interaction Between HSK16149 Capsules and Metformin Hydrochloride Tablets in Healthy Subjects

This study is a single-center, open, single-arm study, conducted in healthy Chinese populations, and plans to enroll 22 healthy adult subjects (the ratio of either sex is not less than 1/3).

Study Overview

• Status: Recruiting
• Conditions: Diabetic Neuropathies; Diabetic Neuropathy Peripheral
• Intervention / Treatment: Drug: HSK16149; Drug: Metformin Hydrochloride tablet; Drug: HSK16149+Metformin（phase 3）

Detailed Description

All subjects received the following drugs:

Phase 1-HSK16149 capsules for single use: D1-D4 oral HSK16149 capsules 80 mg BID, D5 only oral HSK16149 capsules 80 mg in the morning on an empty stomach; wash-out period is about 4 days (D5-D8); Phase 2-Metformin hydrochloride tablets for single use: D9-D11 oral metformin hydrochloride tablets 500 mg BID, D12 only take 500 mg metformin hydrochloride tablets in the morning on an empty stomach; wash-out period is about 4 days (D12-D15); Phase 3-Combined use of HSK16149 capsules and metformin hydrochloride tablets: D16-D19 oral metformin hydrochloride tablets 500 mg BID, D16-D19 oral HSK16149 80 mg BID; D20 oral metformin hydrochloride tablets 500 mg and HSK16149 capsules 80 mg in the morning on an empty stomach.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kai Chen, PhD; Phone Number: 028-82378557; Email: chenk@haisco.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Mingxia Wang, PhD; Phone Number: 0331-86095794; Email: Dgyxxli@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-50 years old (including 18 and 50 years old), healthy male or female;
2. Weight: male ≥50 kg, female ≥45kg; body mass index (BMI) in the range of 19-28kg/m2 (including 19 and 28);
3. Serum creatinine during the screening period is within the normal range, or creatinine clearance rate (CCr) ≥80mL/min;
4. Physical examination, vital signs, 12-lead electrocardiogram (ECG), chest X-ray (posterior anterior position), and laboratory examination indicators are normal or abnormal and have no clinical significance;
5. Agree to have no birth plan and be able to take reliable contraceptive measures within 3 months after the end of the trial; Be able to communicate well with researchers, fully understand the purpose and requirements of this trial, voluntarily participate in clinical trials and sign written informed consent.

Exclusion Criteria:

1. Those who are known to have a history of allergies, allergic diseases or allergies to the research preparation and any of its ingredients or related preparations, or those who have a history of pregabalin or gabapentin allergy;
2. Those who have special requirements for diet and cannot comply with a unified diet;
3. Those who have had angioedema in the past;
4. Clinically significant dizziness or vertigo, or a history of inner ear diseases known to cause dizziness or vertigo;
5. QTcF>450 milliseconds (msec) found in the screening period inspection;
6. People with insomnia, anxiety disorder, depression disorder or other mental disorders;
7. Those who use any caffeine-rich food or drink (coffee, tea, cola, chocolate, etc.) within 48 hours before the first administration of the test drug, or who do not agree to prohibit the use of any caffeine-rich food or drink during the test period ；
8. Any disease history or current disease that may affect the safety evaluation of subjects or the internal process of experimental drugs, including the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, blood system, immunology, Psychiatry, metabolic abnormalities, gastrointestinal surgery (except appendicitis surgery), etc.;
9. Those who donate blood or lose blood ≥400 mL or have blood transfusion within 3 months before the first administration of the test drug;
10. Any drug that inhibits or induces liver drug-metabolizing enzymes (such as inducers barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole) has been used within 30 days before the first administration of the test drug; Serotonin reuptake inhibitor (SSRI) antidepressants, cimetidine, diltiazem macrolides, nitroimidazoles, sedative hypnotics, verapamil, fluoroquinolones, antihistamines), or Any prescription drugs, over-the-counter drugs and herbal medicines other than the above-mentioned drugs were taken within 14 days prior to the administration of the test drugs;
11. Those who have participated in other drug clinical trials within 3 months before the first administration of the experimental drug;
12. At this stage or have been drug users, or those who have been screened positive for drug abuse (screening items include: morphine, tetrahydrocannabinolic acid, methamphetamine, dimethylenedioxyamphetamine, Ketamine and cocaine);
13. Alcoholics or frequent alcoholics in the 3 months before the test, that is, drinking more than 21 units of alcohol per week (1 unit = 360mL beer or 45 mL 40% alcoholic spirits or 150 mL wine), or alcohol exhalation Test value> 0mg/ml;
14. Smokers or those who smoked more than 10 cigarettes per day within 3 months before the first administration, or who could not comply with the ban on smoking during the trial period;
15. One or more of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody or human immunodeficiency virus (HIV) antibody is positive;
16. Women during pregnancy or lactation;Researchers believe that subjects have poor compliance or other factors that are not suitable for participating in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK16149; HSK16149（D1-D5）	Drug: HSK16149; HSK16149 capsules for single use: D1-D4 oral HSK16149 capsules 80 mg BID, D5 only oral HSK16149 capsules 80 mg in the morning on an empty stomach; wash-out period is about 4 days (D5-D8); Other Names: HSK16149（phase 1）
Experimental: Metformin	Drug: Metformin Hydrochloride tablet; Metformin hydrochloride tablets for single use: D9-D11 oral metformin hydrochloride tablets 500 mg BID, D12 only take 500 mg metformin hydrochloride tablets in the morning on an empty stomach; wash-out period is about 4 days (D12-D15); Other Names: Metformin hydrochloride tablets（phase 2）
Experimental: HSK16149+Metformin	Drug: HSK16149+Metformin（phase 3）; Combined use of HSK16149 capsules and metformin hydrochloride tablets: D16-D19 oral metformin hydrochloride tablets 500 mg BID, D16-D19 oral HSK16149 80 mg BID; D20 oral metformin hydrochloride tablets 500 mg and HSK16149 capsules 80 mg in the morning on an empty stomach.; Other Names: HSK16149 capsules and Metformin hydrochloride tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak concentration	-30 minutes before administration until 24 hours after administration
AUC0-t, AUC0-∞	Area under the concentration-time curve	-30 minutes before administration until 24 hours after administration
Tmax	time to peak observed	-30 minutes before administration until 24 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE/serious AE	Adverse event/serious adverse event	From screening up to 6 weeks

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.
• Collaborators: The Fourth Hospital of Hebei Medical University
• Investigators: Study Director: Mingxia Wang, PhD, Medical Ethics Committee of theThe fourth hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): August 15, 2021

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: HSK16149-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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