The Single, Multiple Dose and Food Effect Study of SHR2285 Tablets on Pharmacokinetics and Pharmacodynamics in Healthy Subjects

NCT04472819 | Completed Phase 1

• 1 other identifier: SHR2285-104
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a randomized, doubled-blinded, placebo-controlled, Phase I trials. The study is divided into two parts. The first part is a single-dose escalated study (SAD,part 1A ) and food effect study (SAD, part 1B ) in healthy subjects. The second part is a multi-dose escalated study (MAD) in healthy subjects.

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (5)

• Number of subjects with adverse events and severity of adverse events.

  Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration

• Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.

  Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration

• Time to maximum observed serum concentration (Tmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.

  Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration

• Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.

  Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration

• Area under the plasma concentration versus time curve (AUC0-last) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.

  Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration

Secondary Outcomes (11)

• Maximum observed serum concentration (Cmax) for single dose of SHR2285.

  Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration

• Time to maximum observed serum concentration (Tmax) for single dose of SHR2285.

  Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration

• Time to elimination half-life (T1/2) for single dose of SHR2285.

  Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration

• Area under the plasma concentration versus time curve (AUC0-last) for single dose of SHR2285.

  Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration

• Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285.

  Pre-dose to day 9 after multiple dose administration

Study Arms (6)

SHR2285 Part 1A

EXPERIMENTAL

Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration

Drug: SHR2285 tablet

Placebo Part 1A

PLACEBO COMPARATOR

Single ascending doses of placebo orally

Drug: Placebo

SHR2285 Part 1B

EXPERIMENTAL

Participant received one dose of SHR2285 tablet as single-dose oral administration

Drug: SHR2285 tablet

Placebo Part 1B

PLACEBO COMPARATOR

Single doses of placebo orally

Drug: Placebo

SHR2285 Part 2

EXPERIMENTAL

Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration

Drug: SHR2285 tablet

Placebo Part 2

PLACEBO COMPARATOR

Multiple ascending doses of placebo orally

Drug: Placebo

Interventions

SHR2285 tablet DRUG

single dose or multi-dose

SHR2285 Part 1A; SHR2285 Part 1B; SHR2285 Part 2

Placebo DRUG

single dose or multi-dose

Placebo Part 1A; Placebo Part 1B; Placebo Part 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects, aged 18-55 (including boundary);
• Body mass index (BMI) between 18 to 28 kg/m2 (including boundary), male body weight ≥50 kg and \<90 kg , female body weight ≥45kg and \<90kg;
• Participant with no clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters.
• Understand the study procedures and methods, voluntary to participate in the study and signed the informed consent.

You may not qualify if:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin \> upper limit of normal (ULN) during screening/baseline.
• Serum creatinine\> ULN during screening/baseline.
• Positive faecal occult blood
• Abnormal coagulation function.
• A clinical history of coagulation dysfunction; subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
• Subjects with severe head trauma or head surgery within 2 years or surgery within 3 months prior to the screening.
• Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before administration.
• Human immunodeficiency virus antibody, syphilis serological examination, hepatitis b virus surface antigen, hepatitis c virus antibody were positive.
• months prior to screening involved in any drug or medical device clinical studies or within 5 half-life of drugs before screening.
• Female subjects who did not receive contraception at least 30 days before administration and etc.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (2)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410006, China

Location

Related Publications (1)

• Xu J, Zhao N, Huang J, Li J, Zhao X, Xiang Q, Yang S, Dong Y, Wang H, Li Y, Yang G, Cui Y. The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers. Clin Drug Investig. 2023 Jun;43(6):435-445. doi: 10.1007/s40261-023-01281-8. Epub 2023 Jun 16.

  PMID: 37326942 DERIVED

MeSH Terms

Conditions

Thrombosis

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: July 15, 2020
• Study Start: August 28, 2020
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)