Clinical trial NCT05012761: The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers
Official title: A Phase I Bridging Study to Evaluate the PK, Safety and Tolerability of SR419 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Shanghai SIMR Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled phase I PK bridging study to evaluate the PK, safety and tolerability of SR419 in healthy subjects.

Detailed description: The study is a Phase I study to evaluate the PK, safety, and tolerability of SR419 in healthy volunteers. The study will include 3 single-ascending-dose (SAD) cohorts and 2 multiple-dose cohorts (Part A and part B respectively), a total of 5 cohorts, and each cohort includes 3 stages: screening and baseline, treatment and safety monitoring, and safety follow-up.

Eligibility criteria: Inclusion Criteria:

1. Healthy males and females who are 18 to 45 years of age.
2. Based on medical history, physical examination, laboratory examination, chest X-ray, abdominal B-ultrasound, vital signs and ECG, the investigator considered that the results were normal or abnormal but no clinical significance.
3. Bodyweight of male \> 50 kg, Bodyweight of female \> 45 kg and body mass index (BMI) between 18 and28 kg/m2
4. Male subjects must agree to use contraception methods.
5. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. Clinically significant history of central nervous system (CNS) disease, such as cognitive disorder and seizures. History of non-clinically significant mild anxiety (related to social stressors) or situational sleep disturbance \> 6 months ago could be enrolled under the discretion of the Investigators.
2. Known history of renal dysfunction or creatinine clearance \< 90 mL/min (calculated using the Cockcroft-Gault formula) at Screening.
3. Current or chronic history of liver disease or known hepatic or biliary abnormalities.
4. History of regular alcohol consumption within 6 months of screening defined as: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (\~285 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.
5. History of significant drug abuse within one year of screening or use of soft drugs (such as marijuana) within 3 months prior to screening or hard drugs (such as cocaine, methamphetamine, crack) within 1 year prior to screening.
6. History of sensitivity to any of the investigational medicinal products (IMPs), or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation.
7. History of asthma (excluding resolved childhood asthma), severe allergic responses.
8. History of hypercoagulable state or history of thrombosis.
9. A positive Hepatitis B surface antigen, positive Hepatitis C antibody and positive test for human immunodeficiency virus (HIV) antibody.
10. within 6 months of screening, Smoking more than 4 cigarettes per day (including e-cigarettes).
11. A positive drug/alcohol result at Screening or Day -1.
12. Donation or lost in excess of 500 mL of blood within 56 days of Day 1 or donation of plasma within 14 days of Day 1.
13. The subject has participated in a clinical trial within 3 months of receiving IMP.
14. Use of medication other than topical products without significant systemic absorption.
15. Unable to refrain from consumption of Seville oranges, grapefruit or grapefruit juice within 24h prior to the first dose of IMP until the Safety Follow-up visit.
16. Unable to refrain from consumption of alcohol, products containing caffeine or xanthine (such as coffee, tea, cola, chocolate) within 7 days prior to the first dose of IMP until the Safety Follow-up visit.
17. Breast-feeding and/or lactating subject.
18. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Primary outcomes:
measure: Cmax
timeFrame: Up to Day 7
measure: Tmax
timeFrame: Up to Day 7
measure: AUC
timeFrame: Up to Day 7
measure: CL/F
timeFrame: Up to Day 7
measure: t1/2
timeFrame: Up to Day 7
measure: Rac
timeFrame: Up to Day 7
Secondary outcomes:
measure: The frequency and severity of AEs in healthy volunteers administrated with single and repeated oral doses of SR419 capsules
timeFrame: Up to Day12(+7 days) for the safety follow up since Day1
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Clinical Research Center Phase I Clinical Research Unit (SCRC-PCRU)
Study officials:
affiliation: Shanghai Clinical Research Center Phase I Clinical Research Unit (SCRC-PCRU)
name: Chen Yu
role: PRINCIPAL_INVESTIGATOR
References: