Chronic kidney disease
Conditions
Interventions
SAD-C1 Cohort (Monotherapy):DF-003 capsules 60 mg (2×25 mg + 2×5 mg), single oral dose, fasting
SAD-C1 Cohort (Placebo):Placebo capsules 60 mg, single oral dose, fasting
SAD-C2 Cohort (Monotherapy):DF-003 capsules 150 mg (6×25 mg), single oral dose, fasting
SAD-C2 Cohort (Placebo):Placebo capsules 150 mg, single oral dose, fasting
SAD-C3 Cohort (Monotherapy) (Optional):DF-003 capsules, single oral dose, fasting, dose to be adjusted based on safety and PK data
SAD-C3 Cohort (Placebo) (Optional):Placebo capsules, single oral dose, fasting, dose to be adjusted based on safety and PK data
SAD-C4 Cohort (Monotherapy) (Optional):DF-003 capsules, single oral dose, fasting, dose to be adjusted based on safety and PK data
SAD-C4 Cohort (Placebo) (Optional):Placebo capsules, single oral dose, fasting, dose to be adjusted based on safety and PK data
SAD- Food Effects Cohort (Monotherapy) (Optional):DF-003 capsules 60 mg (2×25 mg + 2×5 mg), single oral dose, fed state (to be conducted after 21-day washout)
SAD- Food Effects Cohort (Placebo) (Optional):Placebo capsules 60 mg, single oral dose, fed state (to be conducted after 21-day washout)
MAD-C1 Cohort (Monotherapy):DF-003 capsules, once daily oral administration, fasting, for 14 days, dose to be determined based on SAD results (e.g., starting at 50 mg)
MAD-C1 Cohort (Placebo):Placebo capsules, once daily oral administration, fasting, for 14 days
MAD-C2 Cohort (Monotherapy):DF-003 capsules, once daily oral administration, fasting, for 14 days (or shortened to 7 days based on SAD results), dose to be adjusted based on safety and PK data
MAD-C2 Cohort (Placebo):Placebo capsules, once daily oral administration, fasting, for 14 days (or shortened to 7 days based on SAD results)
MAD-C3 Cohort (Monotherapy):DF-003 capsules, once daily
Sponsors
The third xiangya hospital of Central South University
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent form (ICF); 2. Ability to understand and stated willingness to comply with all study procedures and availability for the duration of the study, and likeliness to complete the study as planned, per the Investigator’s opinion; 3. Healthy adult male or female; 4. If male, meets one of the following criteria: (1) Is able to procreate and agrees not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration in addition to: 1) Having a female partner who is postmenopausal, surgically sterile, or otherwise incapable of becoming pregnant. Or 2) Having a female partner who is a woman of childbearing potential and agrees to use a highly-effective method of contraception from the first study drug administration to at least 90 days after the last study drug administration as detailed in APPENDIX 6. Or (2) Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 180 days prior to the first study drug administration) 5. If female, meets one of the following criteria: (1) Physiological postmenopausal status, defined as the following: 1) amenorrhea for at least 12 months prior to the first study drug administration (without an alternative medical condition); and 2) Follicle stimulating hormone (FSH) levels >= 40 mIU/ml at Screening; 3) In the absence of 12 months of amenorrhea, 2 FSH measurements at least 3 months apart and in the postmenopausal range must be documented. Or (2) Surgical postmenopausal status, defined as having had a bilateral oophorectomy or bilateral salpingo-oophorectomy with FSH levels >= 40 mIU/ml at Screening. Surgically sterile females without elevated FSH levels may be considered of non-childbearing potential status and enrolled in the study at the discretion of the Investigator; FSH will be collected in this population, although this assessment will not count towards determination of their eligibility. 6. Aged at least 18 years but not older than 55 years at the time of Screening; 7. Body mass index (BMI) within 18.0 kg/m^2 to 32.0 kg/m^2, inclusively; 8. Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 3 months prior to the first study drug administration); 9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination, vital signs, eye examination, and/or ECG, as determined by an Investigator; 10. 12-lead ECG that meets the following criteria (ECG intervals will be based on the mean value of triplicate ECGs [rounded to the nearest whole number] collected at Screening): Heart rate: >= 50 to <= 100 beats per minute; QT interval corrected for heart rate (QTc) according to Fridericia’s formula (QTcF) <= 450 ms (males) or <= 470 ms (females); QRS interval < 120 ms; PR interval <= 200 ms.
Exclusion criteria
Exclusion criteria: 1. Female who is lactating; 2. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration; 3. Female using the following systemic contraceptives: oral, patch or vaginal ring, in the 28 days prior to the first study drug administration; 4. Female using hormone replacement therapy in the 28 days prior to the first study drug administration; 5. Female using the following systemic contraceptives: injections or implant, or hormone-releasing intrauterine device in the 13 weeks prior to the first study drug administration; 6. History of tuberculosis (TB), or positive chest X-ray is suggestive of latent or active TB at Screening; 7. History of significant hypersensitivity to products related to DF-003 (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs; 8. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery (with the exception of cholecystectomy and appendectomy) that may affect drug bioavailability; 9. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, rheumatologic, neoplastic, metabolic, or dermatologic disease; 10. Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgment; 11. History or family history of chronic inflammatory skin disease (eg, psoriasis, atopic dermatitis, drug-related rash, or chronic urticaria), or immune or autoimmune related disorders, diseases, or syndromes; 12. Major surgery (eg, requiring general anesthesia) within 12 weeks before Screening, during the study, or within 12 weeks after the last dose of study drug; NOTE: Subjects with planned surgical procedures to be conducted under local anesthesia may participate. 13. Presence of renal dysfunction at Screening (eg, estimated glomerular filtration rate 3 units of alcohol per day, intake of excessive alcohol, acute or chronic); 15. Any clinically significant illness including current acute or chronic infections in the 28 days prior to the first study drug administration; 16. Use of any prescription drugs in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy; 17. Use of St. John’s wort in the 28 days prior to the first study drug administration; 18. Use of any over-the-counter medications 7 days prior to the first study drug administration. Subjects will be reminded that over-the-counter medications include cold preparations, aspirin, vitamins, and natural products used for therapeutic benefits, and antacid preparations; 19. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration; 20. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen, or hepatitis C virus tests; 21. Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject’s risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data; 22. Intake of an IP in the 4 weeks (or 5 half-lives, whichever is longer) prior to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety data (including adverse events (AEs), physical examination, ophthalmologic examination, vital signs, 12-lead electrocardiogram (ECG), Holter monitoring, and clinical laboratory test results); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) parameters (including: Cmax, Tmax, AUC0-T, AUC0-8, Thalf, CL/F, Vz/F); | — |
Countries
China
Contacts
Public ContactYang Guoping
The Third Xiangya Hospital of Central South University
Outcome results
None listed