ADPKD (Autosomal Dominant Polycystic Kidney Disease)
Conditions
Brief summary
This is a single-center, non-randomized, open-label, self-controlled, Phase I clinical trial to evaluate the drug-drug interactions (DDI) of JMKX003142 tablets in healthy adult participants. The study consists of five cohorts (Cohorts 1, 2, 3, 4, and 5). A total of 24 participants are planned enrollment in each of Cohorts 1, 2, 3, and 5, while 16 participants are planned for Cohort 4.
Interventions
3mg once daily (QD) on Day 1 and Day 7
400mg QD on Day 4, 200mg QD from Day 5 to Day 9
DRUGCocktail Substrates (Midazolam Oral Solution, Rosuvastatin Calcium Tablets, and Digoxin Tablets)
Midazolam Oral Solution 2mg, Rosuvastatin Calcium Tablets 5mg and Digoxin Tablets 0.25mg QD on Day 1, Day 8 and Day 21
DRUGCyclosporine Soft Capsules
100 mg twice daily (BID) from Day 4 to Day 9
DRUGOmeprazole Enteric-coated Tablets
40mg QD from Day 4 to Day 8
DRUGEfavirenz Tablets
600mg QD from Day 4 to Day 12
Sponsors
Jemincare
Zhejiang Hangyu Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants are able to return to the study center for follow-up as required by the protocol and are willing to comply with study policies, procedures, and restrictions; capable of effective communication with the investigator and completing study-related materials; able to understand the contents of the Informed Consent Form (ICF) and sign the written ICF prior to any study procedures. 2. Healthy Chinese male or female subjects, as determined by medical history and physical examination. At the time of signing the Informed Consent Form (ICF), aged 18-45 years (inclusive) ; body weight ≥ 50 kg for males or ≥ 45 kg for females; and Body Mass Index (BMI) within the range of 19.0-26.0 kg/m² (inclusive). 3. Participants were considered healthy by the Investigator based on medical history, baseline physical examination, clinical laboratory assessments, and 12-lead ECG, with all results judged as normal or not clinically significant. 4. Participants of childbearing potential who agree to use effective contraception and have no plans for conception, cryopreservation, or donation of gametes from ICF signature through 3 months after the last dose.
Exclusion criteria
1. Known or suspected hypersensitivity to JMKX003142 (active ingredient or excipients), or a history of hypersensitivity to more than two drugs, foods, or other substances. 2. History or presence of clinically significant diseases in any of the following systems (including but not limited to): cardiovascular, respiratory, gastrointestinal, hematologic, genitourinary, endocrine/metabolic, nervous, psychiatric, musculoskeletal, dermatologic, lymphatic, immune, or sensory organs; or current active local or systemic infection. 3. Any condition increasing the risk of bleeding, such as acute gastritis, active ulcer with hemorrhage, clinically significant thrombocytopenia or anemia, active pathological bleeding, or a history of intracranial hemorrhage. 4. Vital signs meet any of the following criteria at screening: systolic blood pressure ≥ 140 mmHg or \< 90 mmHg; diastolic blood pressure ≥ 90 mmHg or \< 50 mmHg; pulse rate \> 100 bpm or \< 50 bpm; or tympanic temperature ≥ 37.5°C or \< 35°C. 5. Subjects with a history of QTc interval prolongation or a family history of Long QT Syndrome; or those with clinically significant abnormal ECG findings as determined by the Investigator during screening; or a QTcF ≥ 450 ms; or a QRS interval \> 120 ms. 6. Positive for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, Human Immunodeficiency Virus (HIV) antibody, or syphilis serology. 7. Treatment with therapeutic biological products within 3 months (or 5 half-lives, whichever is longer) prior to dosing, or other prescription/non-prescription medications (including vaccines, Traditional Chinese Medicine \[TCM\], dietary supplements, and health products) within 1 month (or 5 half-lives, whichever is longer). 8. Use of any investigational drug within 3 months prior to screening, or current participation in another clinical trial. 9. Major surgery (e.g., requiring general or epidural anesthesia) within 3 months prior to screening, or planned surgical intervention during the study. 10. History of hemophobia, belonephobia, or difficult venous access. 11. Blood donation or blood loss of ≥400 mL within 3 months prior to screening. 12. History of drug dependence/abuse or illicit drug use, or a positive drug screening result. 13. Smoking ≥5 cigarettes per day within 3 months prior to screening, or inability to commit to abstaining from tobacco products during the study, or a positive nicotine screening result. 14. History of heavy alcohol consumption (\>14 units per week; 1 unit ≈ 10 mL alcohol, equivalent to approx. 285 mL beer \[3.5%\], 25 mL spirits \[40%\], or 100 mL wine \[10%\]), inability to abstain from alcohol after screening, or a positive alcohol breath test. 15. Daily consumption of excessive tea, coffee, or caffeine-containing beverages (more than 8 cups per day; 1 cup = 250 mL) within 14 days prior to screening. 16. Ingestion of grapefruit or grapefruit-related citrus fruits (e.g., Seville oranges, pomelos) or fruit products within 3 days prior to dosing. 17. Special dietary requirements, or inability to comply with a standardized diet (e.g., standard meals) and dietary restrictions. 18. Pregnancy or lactation, positive pregnancy test in females, unprotected sexual intercourse with a partner within 14 days prior to screening, use of oral contraceptives within 30 days prior to screening, or use of long-acting injectable or implanted estrogens/progestogens within 6 months prior to screening. 19. Requirement to drive long distances, work at heights, or operate complex machinery during the study. 20. Other conditions that, in the investigator's opinion, would make the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of JMKX003142 and its metabolites | for 120 hours |
| Area Under Curve (AUC) of JMKX003142 and its metabolites | for 120 hours |
| Maximum Plasma Concentration (Cmax) of Midazolam and its metabolites | for 144 hours |
| Area Under Curve (AUC) of of Midazolam and its metabolites | for 144 hours |
| Maximum Plasma Concentration (Cmax) of Rosuvastatin | 144 hours |
| Area Under Curve (AUC) of of Rosuvastatin | for 144 hours |
| Maximum Plasma Concentration (Cmax) of Digoxin | for 144 hours |
| Area Under Curve (AUC) of Digoxin | for 144 hours |
Secondary
| Measure | Time frame |
|---|---|
| Tmax of JMKX003142 and its metabolites | for 120 hours |
| T1/2 of JMKX003142 and its metabolites | for 120 hours |
| CL of JMKX003142 and its metabolites | for 120 hours |
| Tmax of Midazolam and its metabolites | for 144 hours |
| T1/2 of Midazolam and its metabolites | for 144 hours |
| CL of Midazolam and its metabolites | for 144 hours |
| Tmax of Rosuvastatin | for 144 hours |
| T1/2 of Rosuvastatin | for 144 hours |
| CL of Rosuvastatin | for 144 hours |
| Tmax of Digoxin | for 144 hours |
| T1/2 of Digoxin | for 144 hours |
| CL of Digoxin | for 144 hours |
Outcome results
None listed