A Study to Evaluate the Drug-drug Interactions (DDIs) of GP681 With Rosuvastatin, Digoxin, Itraconazole, Oseltamivir in Chinese Healthy Volunteers

Healthy Volunteers Clinical Trial

Official title:

A Four-part, Single-center, Open-label, Phase I Clinical Study to Evaluate the Drug-drug Interactions (DDIs) Between GP681 and Rosuvastatin/Digoxin/Itraconazole/Oseltamivir in Chinese Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05789342
• Other study ID #: GP681-202202
• Status: Completed
• Phase: Phase 1
• Start date: February 15, 2023
• Est. completion date: October 31, 2023

Study information

• Verified date: November 2023
• Source: Jiangxi Qingfeng Pharmaceutical Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a four-part, single-center, Open label phase I clinical study to characterize the DDIs potential of GP681 With Rosuvastatin, Digoxin, Itraconazole or Oseltamivir in Chinese healthy volunteers. This study also aims to evaluate the safety and tolerability of GP681 in the presence of Rosuvastatin, Digoxin, Itraconazole, or Oseltamivir.

Description:

GP681 is a potent polymerase acidic (PA) protein endonuclease inhibitor. This study will be run in four parts to characterize the DDIs potential of GP681 with the expected concomitant drugs (Rosuvastatin, Digoxin, Itraconazole, Oseltamivir) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -1), a baseline period (Day -1), a treatment period, and a follow-up telephone call for safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 31, 2023
• Est. primary completion date: September 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy males or females between the ages of 18 and 55 years, inclusive;

2. Body weight =50.0 kg for males, =45kg for females, and body mass index (BMI) between19-26 kg/m^2(inclusive);

3. Normal physical examination, vital signs, 12-lead ECG, Chest X-ray images (anteroposterior) and clinical laboratory values, or any abnormality that is non-clinically significant;

4. Men must agree to use protocol-specified contraception and also to not donate sperm throughout the study and for at least 3 months after the final dose of study drug

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

Exclusion Criteria:

1. History of allergic conditions or allergic diseases, or a history of allergic reactions attributed to GP681 or any of the ingredients of its formulation or similar drugs. Those who cannot follow a uniform diet for special dietary requirements.

2. Subjects with swallowing difficulties, or have diseases such as hemorrhoids, perianal diseases with regular/bleeding in the stool, habitual constipation or diarrhea, irritable bowel syndrome and inflammatory bowel diseases, affecting drug absorption, distribution, metabolism, excretion or the efficacy and safety of the drug.

3. History of gastrointestinal ulcer or bleeding; Or history of any clinically significant diseases or diseases which may affect the result of this study, such as gastrointestinal, circulatory, respiratory, endocrine, neurological, urinary, hematological, immunological, psychiatric and metabolic diseases;

4. History of organic heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torsade de pointes ventricular tachycardia, ventricular tachycardia, prolonged QT syndrome, or symptoms of prolonged QT syndrome and family history;

5. Patients who have undergone surgery within 6 months before the screening period, or who have undergone major surgery within 28 days, or whose surgical incision is not completely healed; Major surgery includes, but is not limited to, any surgery with a significant risk of bleeding, prolonged general anesthesia, or an open biopsy or significant traumatic injury;

6. Pregnant or lactating female subjects, female subjects with childbearing potential and positive pregnancy test at baseline.

7. History of receiving a live vaccine within 1 month prior to the screening, or is expected to receive a live vaccine during the study.

8. Any positive test result of hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;

9. Received any drugs that inhibit or induce the CYP450 enzyme (i.e., inducers-barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors- SSRI-antidepressant, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative hypnotics, verapamil, fluoroquinolones, antihistamines) 30 days prior to screening period;

10. Received any drugs (including Chinese herbal medicine, vitamins and supplements) within 14 days prior to dosing, or participation in another clinical trial within 3 months before dosing.

11. Those who have lost blood or donated up to 200 mL within 3 months before dosing, or those who plan to donate blood within 1 month after the end of this study;

12. Smoking more than 5 cigarettes per day within 3 months prior to screening,or who cannot stop using any tobacco products during the study period;

13. Average weekly intake of alcohol is more than 21 units alcohol (1 units ˜ 360 mL beer, or 45 mL spirits with 40% content, or 150 mL wine) within the 3 months prior to dosing, or a positive ethanol breath test at screening;

14. Substance abuse or use of soft drugs (e.g., marijuana) or use of hard drugs (e.g., cocaine, amphetamines, phenylcyclohexidine, etc.); Or screening for positive urine drug abuse (drug) tests;

15. Habitual or excessive consumption (more than 8 cups, 1cup=250mL) of grapefruit juice, tea, coffee and/or caffeinated beverages;

16. Subjects who are intolerant to venipuncture or have a history of fainting blood or acupuncture

17. Inability to take normal hospital diet;

18. Subjects with poor compliance, or not suitable for this study as judged by the investigator.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• GP681
GP681, tablet, oral
• Rosuvastatin
Rosuvastatin, tablet, oral
• Digoxin
Digoxin, tablet, oral
• Itraconazole
Itraconazole, capsule, oral
• Oseltamivir
Oseltamivir, capsule, oral

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Jiangxi Qingfeng Pharmaceutical Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part one: Peak plasma concentration (Cmax) of Rosuvastatin		Day 1 to Day 4, and Day 8 to Day 11
Primary	Part one: Area under the plasma concentration versus time curve (AUC) of Rosuvastatin		Day 1 to Day 4, and Day 8 to Day 11
Primary	Part two: Peak plasma concentration (Cmax) of Digoxin		Day 1 to Day8, and Day 15 to Day 22
Primary	Part two: Area under the plasma concentration versus time curve (AUC) of Digoxin		Day 1 to Day 8, and Day 15 to Day 22
Primary	Part three: Peak plasma concentration (Cmax) of GP681		Day 1 to Day12, and Day26 to Day 37
Primary	Part three: Area under the plasma concentration versus time curve (AUC) of GP681		Day 1 to Day 12, and Day26 to Day 37
Primary	Part Four: Peak plasma concentration (Cmax) of GP681		264 hours after GP681 administration
Primary	Part Four: Area under the plasma concentration versus time curve (AUC) of GP681		264 hours after GP681 administration
Primary	Part Four: Peak plasma concentration (Cmax) of Oseltamivir		12 hours after Oseltamivir administration
Primary	Part Four: Area under the plasma concentration versus time curve (AUC) of Oseltamivir		12 hours after Oseltamivir administration