History of Changes for Study: NCT04036656

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Version	A	B	Submitted Date	Changes
1			July 25, 2019	None (earliest Version on record)

Study Identification


Unique Protocol ID:	SYHA136201901/PRO-I
Brief Title:	Phase I Study of Direct Coagulation Factor Xa Inhibitor SYHA136 Tablets in Chinese Healthy Volunteers
Official Title:	Single-center, Randomized, Double-blind, Placebo-controlled, Single Dose Ascending Trial of SYHA 136 Tablets in Healthy Subjects
Secondary IDs:

Study Status


Record Verification:	July 2019
Overall Status:	Unknown status [Previously: Not yet recruiting]
Study Start:	August 2019
Primary Completion:	January 2020 [Anticipated]
Study Completion:	May 2020 [Anticipated]

First Submitted:	July 23, 2019
First Submitted that Met QC Criteria:	July 25, 2019
First Posted:	July 30, 2019 [Actual]

Last Update Submitted that Met QC Criteria:	July 25, 2019
Last Update Posted:	July 30, 2019 [Actual]

Sponsor/Collaborators


Sponsor:	CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	No
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

Brief Summary:

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.

Detailed Description:

Conditions


Conditions:	Venous Thrombosis
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Prevention
Study Phase:	Phase 1
Interventional Study Model:	Parallel Assignment
Number of Arms:	8
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	56 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
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

Outcome Measures


Primary Outcome Measures:
1.	Adverse Events (AEs) [ Time Frame: From Screening period to 12 Days Post dose ] Number of participants that experience Adverse Events (AEs)
2.	Serious Adverse Events (SAEs) [ Time Frame: From Screening period to 12 Days Post dose ] Number of participants that experience Serious Adverse Events (SAEs)
3.	clinically significant laboratory assessment abnormalities [ Time Frame: Up to 72 hours Post dose ] Number of participants with clinically significant laboratory assessment abnormalities
4.	clinically significant 12-lead electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 72 hours Post dose ] Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
5.	clinically significant physical examination abnormalities [ Time Frame: Up to 72 hours Post dose ] Number of participants with clinically significant physical examination abnormalities
Secondary Outcome Measures:
1.	Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast)
2.	Area under the concentration-time curve from time 0 to infinity (AUCinf) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Area under the concentration-time curve from time 0 to infinity (AUCinf)
3.	Maximum observed concentration (Cmax) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Maximum observed concentration (Cmax)
4.	Time to reach maximum observed concentration (Tmax) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Time to reach maximum observed concentration (Tmax)
5.	Terminal elimination half-life (t1/2) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Terminal elimination half-life (t1/2)
6.	Apparent total body clearance (CL/F) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Apparent total body clearance (CL/F)
7.	Apparent volume of distribution (Vz/F) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Apparent volume of distribution (Vz/F)
8.	Amount of SYHA136 excreted in urine (Aeu) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Amount of SYHA136 excreted in urine (Aeu)
9.	Renal clearance (CLr) [ Time Frame: Up to 72 hours Post dose ] PK Assessment - Renal clearance (CLr)
10.	Activated Partial Thromboplastin Time(aPTT) [ Time Frame: Up to 48 hours Post dose ] PD Assessment-Activated Partial Thromboplastin Time(aPTT)
11.	Fibrinogen(Fbg) [ Time Frame: Up to 48 hours Post dose ] PD Assessment-Fibrinogen(Fbg)
12.	Thrombin Time(TT) [ Time Frame: Up to 48 hours Post dose ] PD Assessment-Thrombin Time(TT)
13.	International Normalized Ratio(INR) [ Time Frame: Up to 48 hours Post dose ] PD Assessment-International Normalized Ratio(INR)
14.	Anti-coagulation Factor Xa assays(AXA) [ Time Frame: Up to 48 hours Post dose ] PD Assessment-Anti-coagulation Factor Xa assays(AXA)

Eligibility


Minimum Age:	18 Years
Maximum Age:	40 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: When subject signs the informed contest, 18≤ age ≤ 40, Male or female; Body weight: male ≥50 kg, female ≥45 kg. Body mass index (BMI) of 19.0 to 26.0 kg/m², inclusive; 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; 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; Subjects who voluntarily signed the informed consent and are able to cooperate to complete the test according to the protocal. Exclusion Criteria: Allergic history to more than one drug or other serious allergic rhistory; 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. 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.); History of severe head trauma in 2 years; Severe gastrointestinal diseases occurred within three months before signing informed consent, which affected drug absorption; Have a disease which Haemorrhage could cause serious consequences, such as peptic ulcer; 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; 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; 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; 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; History of drugs or drug abuse or alcoholics or drug abuse screening shows positive response; 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; Smokers: The average daily smoking volume was more than 5 cigarettes within six months before signing the informed consent; 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); Positive with serum immunological test for HBsAg, Anti-HCV, Anti-HIV or Anti-TP; QTc interval≥450 ms, electrocardiogram abnormality with clinical significance, or prolonged history of QTc interval; Abnormal results of chest X-ray (posterior and anterior) with clinical significance; 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; Not suitable for this trial according to the investigator.

Contacts/Locations


Locations:

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: