Phase I Study of Direct Coagulation Factor Xa Inhibitor SYHA136 Tablets in Chinese Healthy Volunteers

Single-center, Randomized, Double-blind, Placebo-controlled, Single Dose Ascending Trial of SYHA 136 Tablets in Healthy Subjects

The trial used single-center, randomized, double-blind, placebo-controlled, single-dose ascending study.

The trial planned to enroll fifty-six healthy volunteers. The subjects were allocated to eight dose groups, including 0.5 mg (3+1), 1 mg (3+1), 2.5 mg (6+2), 5 mg (6+2), 10 mg (6+2), 20 mg (6+2), 35 mg(6+2) and 50 mg (6+2). Each dose group was allocated test drugs and placebos according to the proportion of subjects in the brackets mentioned above.

Study Overview

• Status: Unknown
• Conditions: Venous Thrombosis
• Intervention / Treatment: Drug: SYHA136 0.5 mg; Drug: Placebo matching SYHA136 0.5 mg; Drug: SYHA136 1 mg; Drug: Placebo matching SYHA136 1 mg; Drug: SYHA136 2.5 mg; Drug: Placebo matching SYHA136 2.5 mg; Drug: SYHA136 5 mg; Drug: Placebo matching SYHA136 5 mg; Drug: SYHA136 10 mg; Drug: Placebo matching SYHA136 10 mg; Drug: SYHA136 20 mg; Drug: Placebo matching SYHA136 20 mg; Drug: SYHA136 35 mg; Drug: Placebo matching SYHA136 35 mg; Drug: SYHA136 50 mg; Drug: Placebo matching SYHA136 50 mg

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. When subject signs the informed contest, 18≤ age ≤ 40, Male or female;
2. Body weight: male ≥50 kg, female ≥45 kg. Body mass index (BMI) of 19.0 to 26.0 kg/m², inclusive;
3. Subject's with normal or or abnormity without clinical significance judged by the investigator by physical examination, vital signs, electrocardiogram, blood routine, blood biochemistry, coagulation tests, fecal occult blood, urine routine, serological tests and other important indicators;
4. All subjects who adopt effective non-hormonal contraceptive measures (such as condoms, intrauterine devices without drugs, etc.) from the signing of informed consent to three months after the end of the study;
5. Subjects who voluntarily signed the informed consent and are able to cooperate to complete the test according to the protocal.

Exclusion Criteria:

1. Allergic history to more than one drug or other serious allergic rhistory;
2. Serious diseases of the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, blood system, metabolic disorders or other diseases (such as history of psychosis, malignant tumors, etc.)In the past or now, which were not suitable for clinical trials.
3. History of abnormal bleeding or coagulation disorders (e.g. prone to bruising, gum bleeding, prolonged bleeding after tooth extraction, joint hemorrhage, menorrhagia, postpartum hemorrhage, vitamin K deficiency, haemorrhagic diseases caused by acquired coagulation factor antibodies, trauma, wound or post-operative bleeding, etc.);
4. History of severe head trauma in 2 years;
5. Severe gastrointestinal diseases occurred within three months before signing informed consent, which affected drug absorption;
6. Have a disease which Haemorrhage could cause serious consequences, such as peptic ulcer;
7. Had undergone surgery within six months before signing the informed consent; planned to undergo surgery (including cosmetic surgery, dental surgery and oral surgery) within two weeks after the end of the trial; or planned to take part in vigorous exercise (including physical contact exercise or collision exercise) during the trial;
8. Bleed or donated more than 400 mL within three months before signing informed consent, or planned to donate blood during the study or within one month after the end of the trial;
9. Have taken any prescription drugs, nonpreserip drugs, biological products, traditional Chinese medicines, herbal medicines, vitamin dietary supplements and health products within four weeks before signing the informed consent or use oral long-acting contraceptives or implanted long-acting contraceptives;
10. Subjects participating in other clinical trials and taking trial products, or participated in any other clinical trials of drugs within three months before signing the informed consent;
11. History of drugs or drug abuse or alcoholics or drug abuse screening shows positive response;
12. current or past alcoholics (drinking more than 14 standard units per week, 1 Standard unit containing 14g alcohol, such as 360 mL beer or 40% spirits or 150 mL wines with 45 mL alcohol), or alcohol breath test positive;
13. Smokers: The average daily smoking volume was more than 5 cigarettes within six months before signing the informed consent;
14. Habitually consume excessive caffeine-containing beverages or foods, or foods that may affect drug metabolism within four weeks before signing informed consent. Such as: coffee (no more than 1100 mL per day), tea (no more than 2200 mL per day), cola (no more than 2200 mL per day), functional drinks (no more than 1100 mL per day), chocolate (no more than 510 g per day);
15. Positive with serum immunological test for HBsAg, Anti-HCV, Anti-HIV or Anti-TP;
16. QTc interval≥450 ms, electrocardiogram abnormality with clinical significance, or prolonged history of QTc interval;
17. Abnormal results of chest X-ray (posterior and anterior) with clinical significance;
18. Female subjects: positive pregnancy tests or pregnant or breast-feeding or planning to conceive, who plan to conceive within three months from the signing of informed consent to the end of the study; male subjects: whose partners plan to conceive or plan to donate sperm within three months from the signing of informed consent to the end of the study;
19. Not suitable for this trial according to the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1:SYHA136 0.5 mg or Placebo matching SYHA136 0.5 mg; Participants will receive a single oral dose of SYHA136 0.5 mg or Placebo matching SYHA136 0.5 mg under fasted conditions.	Drug: SYHA136 0.5 mg; oral tablet; Drug: Placebo matching SYHA136 0.5 mg; oral tablet
Experimental: Cohort 2:SYHA136 1 mg or Placebo matching SYHA136 1 mg; Participants will receive a single oral dose of SYHA136 1 mg or Placebo matching SYHA136 1 mg under fasted conditions.	Drug: SYHA136 1 mg; oral tablet; Drug: Placebo matching SYHA136 1 mg; oral tablet
Experimental: Cohort 3:SYHA136 2.5 mg or Placebo matching SYHA136 2.5 mg; Participants will receive a single oral dose of SYHA136 2.5 mg or Placebo matching SYHA136 2.5 mg under fasted conditions.	Drug: SYHA136 2.5 mg; oral tablet; Drug: Placebo matching SYHA136 2.5 mg; oral tablet
Experimental: Cohort 4:SYHA136 5 mg or Placebo matching SYHA136 5 mg; Participants will receive a single oral dose of SYHA136 5 mg or Placebo matching SYHA136 5 mg under fasted conditions.	Drug: SYHA136 5 mg; oral tablet; Drug: Placebo matching SYHA136 5 mg; oral tablet
Experimental: Cohort 5:SYHA136 10 mg or Placebo matching SYHA136 10 mg; Participants will receive a single oral dose of SYHA136 10 mg or Placebo matching SYHA136 10 mg under fasted conditions.	Drug: SYHA136 10 mg; oral tablet; Drug: Placebo matching SYHA136 10 mg; oral tablet
Experimental: Cohort 6:SYHA136 20 mg or Placebo matching SYHA136 20 mg; Participants will receive a single oral dose of SYHA136 20 mg or Placebo matching SYHA136 20 mg under fasted conditions.	Drug: SYHA136 20 mg; oral tablet; Drug: Placebo matching SYHA136 20 mg; oral tablet
Experimental: Cohort 7:SYHA136 35 mg or Placebo matching SYHA136 35 mg; Participants will receive a single oral dose of SYHA136 35 mg or Placebo matching SYHA136 35 mg under fasted conditions.	Drug: SYHA136 35 mg; oral tablet; Drug: Placebo matching SYHA136 35 mg; oral tablet
Experimental: Cohort 1:SYHA136 50 mg or Placebo matching SYHA136 50 mg; Participants will receive a single oral dose of SYHA136 50 mg or Placebo matching SYHA136 50 mg under fasted conditions.	Drug: SYHA136 50 mg; oral tablet; Drug: Placebo matching SYHA136 50 mg; oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of participants that experience Adverse Events (AEs)	From Screening period to 12 Days Post dose
Serious Adverse Events (SAEs)	Number of participants that experience Serious Adverse Events (SAEs)	From Screening period to 12 Days Post dose
clinically significant laboratory assessment abnormalities	Number of participants with clinically significant laboratory assessment abnormalities	Up to 72 hours Post dose
clinically significant 12-lead electrocardiograms (ECGs) abnormalities	Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities	Up to 72 hours Post dose
clinically significant physical examination abnormalities	Number of participants with clinically significant physical examination abnormalities	Up to 72 hours Post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast)	PK Assessment - Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast)	Up to 72 hours Post dose
Area under the concentration-time curve from time 0 to infinity (AUCinf)	PK Assessment - Area under the concentration-time curve from time 0 to infinity (AUCinf)	Up to 72 hours Post dose
Maximum observed concentration (Cmax)	PK Assessment - Maximum observed concentration (Cmax)	Up to 72 hours Post dose
Time to reach maximum observed concentration (Tmax)	PK Assessment - Time to reach maximum observed concentration (Tmax)	Up to 72 hours Post dose
Terminal elimination half-life (t1/2)	PK Assessment - Terminal elimination half-life (t1/2)	Up to 72 hours Post dose
Apparent total body clearance (CL/F)	PK Assessment - Apparent total body clearance (CL/F)	Up to 72 hours Post dose
Apparent volume of distribution (Vz/F)	PK Assessment - Apparent volume of distribution (Vz/F)	Up to 72 hours Post dose
Amount of SYHA136 excreted in urine (Aeu)	PK Assessment - Amount of SYHA136 excreted in urine (Aeu)	Up to 72 hours Post dose
Renal clearance (CLr)	PK Assessment - Renal clearance (CLr)	Up to 72 hours Post dose
Activated Partial Thromboplastin Time(aPTT)	PD Assessment-Activated Partial Thromboplastin Time(aPTT)	Up to 48 hours Post dose
Fibrinogen(Fbg)	PD Assessment-Fibrinogen(Fbg)	Up to 48 hours Post dose
Thrombin Time(TT)	PD Assessment-Thrombin Time(TT)	Up to 48 hours Post dose
International Normalized Ratio(INR)	PD Assessment-International Normalized Ratio(INR)	Up to 48 hours Post dose
Anti-coagulation Factor Xa assays(AXA)	PD Assessment-Anti-coagulation Factor Xa assays(AXA)	Up to 48 hours Post dose

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2019
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: SYHA136201901/PRO-I

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