Clinical trial NCT05789342: A Study to Evaluate the Drug-drug Interactions (DDIs) of GP681 With Rosuvastatin, Digoxin, Itraconazole, Oseltamivir in Chinese Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Jiangxi Qingfeng Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-29
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part one: Peak plasma concentration (Cmax) of Rosuvastatin
timeFrame: Day 1 to Day 4, and Day 8 to Day 11
measure: Part one: Area under the plasma concentration versus time curve (AUC) of Rosuvastatin
timeFrame: Day 1 to Day 4, and Day 8 to Day 11
measure: Part two: Peak plasma concentration (Cmax) of Digoxin
timeFrame: Day 1 to Day8, and Day 15 to Day 22
measure: Part two: Area under the plasma concentration versus time curve (AUC) of Digoxin
timeFrame: Day 1 to Day 8, and Day 15 to Day 22
measure: Part three: Peak plasma concentration (Cmax) of GP681
timeFrame: Day 1 to Day12, and Day26 to Day 37
measure: Part three: Area under the plasma concentration versus time curve (AUC) of GP681
timeFrame: Day 1 to Day 12, and Day26 to Day 37
measure: Part Four: Peak plasma concentration (Cmax) of GP681
timeFrame: 264 hours after GP681 administration
measure: Part Four: Area under the plasma concentration versus time curve (AUC) of GP681
timeFrame: 264 hours after GP681 administration
measure: Part Four: Peak plasma concentration (Cmax) of Oseltamivir
timeFrame: 12 hours after Oseltamivir administration
measure: Part Four: Area under the plasma concentration versus time curve (AUC) of Oseltamivir
timeFrame: 12 hours after Oseltamivir administration
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
Study officials:
affiliation: China-Japan Friendship Hospital
name: Jintong Li
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: Gang Cui
role: PRINCIPAL_INVESTIGATOR
References: