Paroxysmal Nocturnal Hemoglobinuria, PNH
Conditions
Brief summary
Phase I Study Evaluating Safety, Tolerability, PK and PD of Single and Multiple Doses of TUL321 Capsule in Healthy Participants and Food Effect on PK
Detailed description
Primary Objective: To evaluate the safety and tolerability following single and multiple oral dministrations of TUL321 capsules in healthy participants. Secondary Objectives: 1. To characterize the pharmacokinetic (PK) profiles following single and multiple oral administrations of TUL321 capsules in healthy participants; 2. To evaluate the effect of a high-fat meal on the PK profiles after a single oral administration of TUL321 capsules in healthy participants; 3. To preliminarily assess the in vivo biotransformation and mass balance characteristics following single oral administration of TUL321 capsules; 4. To characterize the pharmacodynamic (PD) profiles following single and multiple oral administrations of TUL321 capsules in healthy participants; 5. To evaluate the effect of single oral administration of TUL321 capsules on the QT/QTc interval.
Interventions
DRUGPart1: TUL321
orally, 20 mg、50 mg、 100 mg、200 mg、400 mg and 600 mg
DRUGPart1: Placebo
Oral placebo capsules matching TUL321 capsules
DRUGPart2: TUL321
orally, 50 mg QD、100 mg QD、300 mg QD、50 mg BID
DRUGPart2: Placebo
Oral placebo capsules matching TUL321 capsules
Sponsors
Zhuhai United Laboratories Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants can communicate well with investigators, fully understand the study, volunteer to take part, comply with all study requirements, and sign written informed consent before study procedures. 2. Age 18-45 years (inclusive) at informed consent, male or female. 3. Weight ≥50.0 kg for males, ≥45.0 kg for females; BMI 19.0-26.0 kg/m² (inclusive). 4. Female participants with child-bearing potential, and male participants whose partners have child-bearing potential: no pregnancy, sperm or egg donation from consent to 3 months after last dose, and willing to use study-required contraception. 5. For MAD-only participants: receive ACYW135 meningococcal vaccine and pneumococcal vaccine at least 14 days before first dose. No re-vaccination is needed if pneumococcal vaccine was given within 5 years, or ACYW135 meningococcal vaccine within 3 years prior to first dose.
Exclusion criteria
1. Suspected or confirmed allergy to investigational product or its similar components; or history of multiple drug/food allergies. 2. Past history of tuberculosis infection or active tuberculosis at screening. 3. Known or suspected history of immunodeficiency, inherited or acquired complement deficiency. 4. Confirmed active systemic bacterial, viral or fungal infection within 2 weeks before screening. 5. History of confirmed encapsulated bacterial infection within 6 months before screening, including but not limited to meningococcus, streptococcus pneumoniae, Haemophilus influenzae type b. 6. Clinically significant abnormal findings in laboratory tests, physical examination, vital signs, ECG, chest X-ray or abdominal ultrasound at screening. 7. QTcF (Fridericia correction) ≥450 ms at screening; or other risk factors for torsades de pointes (TdP), such as heart failure, hypokalemia, hypomagnesemia, family history of long QT syndrome. 8. eGFR \<90 mL/min/1.73 m² (calculated by CKD-EPI formula) at screening. 9. Positive for HBsAg, anti-HCV, anti-HIV or syphilis-specific antibody at screening. 10. Received other vaccines not specified in the protocol within 1 month before screening, or plan to receive such vaccines during the study. 11. Participated in another interventional clinical trial within 3 months before screening (excluding subjects who only completed screening without enrollment, or enrolled but did not receive study treatment). 12. Average daily cigarette consumption \>5 cigarettes within 3 months before screening. 13. History of drug/substance abuse within 6 months before screening, or positive drug abuse screening test. 14. Chronic constipation or diarrhea, or other conditions judged by investigator to interfere with fecal sample collection. 15. Required or plan to perform heavy physical labor or strenuous exercise during study participation. 16. Pregnant or lactating women, or women of child-bearing potential with positive pregnancy test at screening. 17. Acute illness or concomitant medication occurs from screening to pre-first-dose. 18. Cannot tolerate high-fat meal (applies only to subjects in the food-effect sub-study). 19. Difficulty swallowing, intolerance to venipuncture, or history of needle-syncope or blood-syncope. 20. Investigator judges that the subject is unsuitable for this study for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Incidence of adverse events (AEs) 2.Changes from baseline in physical examinations, vital signs, electrocardiograms (ECG), and laboratory tests | up to 17 days |
Secondary
| Measure | Time frame |
|---|---|
| Peak plasma concentration (Cmax) | Pre-dose to 144 hours post-dose |
| Time to maximum plasma concentration (Tmax) | Pre-dose to 144 hours post-dose |
| Cumulative amount excreted（Ae）in urine | Pre-dose to 144 hours post-dose |
| Cumulative amount excreted（Ae）in feces | Pre-dose to 144 hours post-dose |
| Alternative pathway (AP) activity | Pre-dose to 144 hours post-dose |
| Bb concentration | Pre-dose to 144 hours post-dose |
Countries
China
Contacts
CONTACTGuoping Yang
PRINCIPAL_INVESTIGATORGuoping Yang
The Third Xiangya Hospital of Central South University
Outcome results
None listed