An Open-label Phase I Study to Evaluate the Drug-drug Interaction of HSK16149 Capsule With Probenecid Tablets or Cimetidine Tablets in Healthy Subjects

• Sponsor: Haisco Pharmaceutical Group Co., Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05881811
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 4.3
• Patients Per Site Per Month: 11.1

Study Details

Study Description

Brief Summary

This study is a single-center, open-label, crossover study, conducted in healthy Chinese populations, and plans to enroll 48 healthy adult subjects (male and female).

Condition or Disease	Intervention/Treatment	Phase
PHN - Post-Herpetic Neuritis	Drug: HSK16149，probenecid, cimetidine	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Phase I Study to Evaluate the Drug-drug Interaction of HSK16149 Capsule With Probenecid Tablets or Cimetidine Tablets in Healthy Subjects
• Actual Study Start Date: Mar 20, 2023
• Anticipated Primary Completion Date: May 31, 2023
• Anticipated Study Completion Date: Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A1 Period 1: HSK16149 single dose on D1, 40mg, fasted; Period 2: HSK16149 single dose on D2, 40mg, fasted; Probenecid QID (500mg) on D1~D4. HSK16149 would be administered 2 hours after the first dose of probenecid on D2.	Drug: HSK16149，probenecid, cimetidine; 40mg HSK16149 single dose, fasted; 500mg probenecid QID from D1~D4 200mg cimetidine QID from D1~D4
Experimental: A2 Period 1: HSK16149 single dose on D2, 40mg, fasted；probenecid QID (500mg) on D1~D4. HSK16149 would be administered 2 hours after the first dose of Probenecid on D2. Period 2: HSK16149 single dose on D1, 40mg, fasted;	Drug: HSK16149，probenecid, cimetidine; 40mg HSK16149 single dose, fasted; 500mg probenecid QID from D1~D4 200mg cimetidine QID from D1~D4
Experimental: B1 Period 1: HSK16149 single dose on D1, 40mg, fasted; Period 2: HSK16149 single dose on D2, 40mg, fasted; Cimetidine QID (200mg) on D1~D4. HSK16149 would be administered 1 hour after the first dose of Cimetidine on D2.	Drug: HSK16149，probenecid, cimetidine; 40mg HSK16149 single dose, fasted; 500mg probenecid QID from D1~D4 200mg cimetidine QID from D1~D4
Experimental: B2 Period 1: HSK16149 single dose on D2, 40mg, fasted; Cimetidine QID (200mg) on D1~D4. HSK16149 would be administered 1 hour after the first dose of Cimetidine on D2. Period 2: HSK16149 single dose on D1, 40mg, fasted;	Drug: HSK16149，probenecid, cimetidine; 40mg HSK16149 single dose, fasted; 500mg probenecid QID from D1~D4 200mg cimetidine QID from D1~D4

Outcome Measures

Primary Outcome Measures

1. Cmax [From the start to 72 hours after administration]

   The maximun plasma concentration of HSK16149

2. AUC0-t [From the start to 72 hours after administration]

   Area under the concentration-time curve from time zero to time of last quantifiable concentration

3. AUC0-inf [From the start to 72 hours after administration]

   Area under the concentration-time curve from time zero extrapolated to infinite time

Secondary Outcome Measures

1. Tmax [From the start to 72 hours after administration]

   Time of maximum concentration

2. t1/2 [From the start to 72 hours after administration]

   half life

3. Vz [From the start to 72 hours after administration]

   Volume of distribution associated with the terminal phase

4. CL [From the start to 72 hours after administration]

   Plasma clearance

5. Ae [From the start to 72 hours after administration]

   Cumulative urinary recovery of unchanged drug

6. Fe [From the start to 72 hours after administration]

   Cumulative urinary recovery fraction of unchanged drug

7. CLr [From the start to 72 hours after administration]

   Renal clearance

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;

2. 18 years to 50 years (inclusive), male and female;

3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-28 kg/m2 (inclusive);

4. Physical examination, vital sign measurements results were deemed appropriate by the investigator;

5. Not in use of any drug within 2 weeks prior to screening;

6. Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration.

Exclusion Criteria:

1. Have an allergic history to the main ingredients and/or any auxiliary materials in the research preparation, allergic diseases or allergies, or allergic history to pregabalin or gabapentin, or allergic history to pregabalin or gabapentin or sulfonamides;

2. Have special requirements for diet and cannot follow the unified diet;

3. The abnormal results of 12-lead electrocardiogram (ECG), chest X-ray (positive position) and routine laboratory tests (blood routine, blood biochemistry, urine routine and coagulation function) during the screening period have clinical significance and are judged by the researchers to be unsuitable to participate in this experiment;

4. In the screening period, male QTcF>450 milliseconds (msec) and female QTcF>470 milliseconds (msec);

5. dizziness or vertigo with clinical significance and requiring medical intervention, or history of inner ear diseases known to cause dizziness or vertigo;

6. Insomnia, anxiety disorder, depression disorder or other mental disorders requiring medical intervention;

7. Use any caffeinated food or drink (coffee, tea, cola, chocolate, etc.) within 48 hours before the first administration of the experimental drug, or disagree with the prohibition of using any caffeinated food or drink during the trial；

8. Suffering from or having suffered from major diseases of cardiovascular system, respiratory system, digestive system, urinary system, hematology, endocrine system, immunity system, skin system or nervous system, including acute diseases or major surgical operations within 3 months before screening；

9. Suffering from or having suffered from diseases of gastrointestinal tract, liver, kidney or other known diseases that interfere with drug absorption, distribution, metabolism or excretion;

10. Blood donation or blood loss of ≥400 mL or more within 3 months before the first administration of the experimental drug;

11. Any drugs that inhibit or induce liver drug metabolizing enzymes have been used within 28 days before the first administration of experimental drugs (such as barbiturates, carbamazepine, phenytoin, glucocorticoid and omeprazole; Inhibitor serotonin reuptake inhibitor (SSRI) antidepressants, cimetidine, diltiazem macrolides, nitroimidazoles, sedatives and hypnotics, verapamil, fluoroquinolones, antihistamines), or any prescription drugs, over-the-counter drugs, Chinese patent medicines and herbs other than the above drugs were taken orally within 14 days before the administration of the experimental drugs;

12. have participated in clinical trials of other drugs within 3 months before the first administration of experimental drugs;

13. Use any live vaccine within 28 days before the first administration of experimental drugs;

14. At present, they are or have been drug users, or they are positive in drug abuse screening (screening items include: morphine, tetrahydrocannabinol, methamphetamine, methylenedioxyamphetamine, ketamine and cocaine);

15. Regular drinkers within 3 months before the first administration of the experimental drug, that is, those who drink more than 14 units of alcohol per week (1 unit =10g pure alcohol, or 285mL beer [4.9% Alc./Vol] or 30 mL spirits [40% Alc./Vol] or 100 mL wine [12% Alc./Vol]), or the alcohol breath test is positive；

16. Smoking more than 5 cigarettes per day (or using a considerable amount of nicotine-containing products) within 3 months before the first administration of experimental drugs, or failing to comply with the smoking ban during the trial;

17. One or more of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody or human immunodeficiency virus (HIV) antibody are positive during the screening period;

18. Have any history of malignant tumor in recent 10 years;

19. pregnant or lactating women;

20. The estimated glomerular filtration rate (eGFR) during the screening period is clinically significant or has a history of kidney calculi's disease and kidney disease;

21. Subjects with poor compliance or other factors that are not suitable for participating in this experiment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Jishuitan Hoispital	Beijing		China

Sponsors and Collaborators

• Haisco Pharmaceutical Group Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Haisco Pharmaceutical Group Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05881811
• Other Study ID Numbers: HSK16149-105
• First Posted: May 31, 2023
• Last Update Posted: May 31, 2023
• Last Verified: May 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuritis; Probenecid; Cimetidine

Study Results

No Results Posted as of May 31, 2023