The Pharmacokinetics (PK), Safety, Tolerability of SR419 in Healthy Volunteers

A Phase I Bridging Study to Evaluate the PK, Safety and Tolerability of SR419 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: SR419 capsules

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Clinical Research Center Phase I Clinical Research Unit (SCRC-PCRU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SR419 capsules; Ascending single and multiple doses of SR419 orally	Drug: SR419 capsules; Ascending single and multiple doses of SR419 orally
Placebo Comparator: Placebo; Ascending single and multiple doses of SR419 placebo orally	Drug: Placebo; Ascending single and multiple doses of placebo orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak plasma concentration	Up to Day 7
Tmax	Time of peak plasma concentration	Up to Day 7
AUC	Area under the plasma concentration-time curve	Up to Day 7
CL/F	Apparent oral clearance	Up to Day 7
t1/2	Terminal half-life	Up to Day 7
Rac	Accumulation ratio	Up to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency and severity of AEs in healthy volunteers administrated with single and repeated oral doses of SR419 capsules	AE: Adverse Event	Up to Day12(+7 days) for the safety follow up since Day1

Collaborators and Investigators

• Sponsor: Shanghai SIMRD Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Chen Yu, Shanghai Clinical Research Center Phase I Clinical Research Unit (SCRC-PCRU)

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2021
• Primary Completion (Actual): December 27, 2021
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: SR419-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No