Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Administration of HS-10356 in Healthy Volunteers

NCT04652297 | Unknown Phase 1

• 1 other identifier: HS-10356-101
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the safety and tolerability of single and multiple oral administration of HS-10356 in healthy volunteers.

Conditions

Healthy

Keywords

HS-10356; Safety; Pharmacokinetics

Outcome Measures

Primary Outcomes (27)

• The incidence, severity, and association of AE, SAE, and adverse events leading to withdrawal from the trial

  SAD: Day1~Day12

• The incidence, severity, and association of AE, SAE, and adverse events leading to withdrawal from the trial

  MAD: Day1~Day25

• Laboratory assessment:Haematology

  Predose, day 6 prior to discharge from hospital in SAD.

• Laboratory assessment:Haematology

  Predose, day4、day7、day10、day14、day19 prior to discharge from hospital in MAD

• Laboratory assessment:Clinical Chemistry

  Predose, day 6 prior to discharge from hospital in SAD.

• Laboratory assessment:Clinical Chemistry

  Predose, day4、day7、day10、day14、day19 prior to discharge from hospital in MAD

• Laboratory assessment:Routine Urinalysis

  Predose, day 6 prior to discharge from hospital in SAD.

• Laboratory assessment:Routine Urinalysis

  Predose, day4、day7、day10、day14、day19 prior to discharge from hospital in MAD

• Laboratory assessment:Coagulation test

  Predose, day 6 prior to discharge from hospital in SAD.

• Laboratory assessment:Coagulation test

  Predose, day4、day7、day10、day14、day19 prior to discharge from hospital in MAD

• Vital signs:Blood pressure

  Within 1 hour before administration,1hour, 2hours, 4hours, 12hours, 24hours, 48hours, 72hours, 96hours, and 120hours after administration in SAD.

• Vital signs:Blood pressure

  Within 1 hour before administration, 1hours, 2hours, 4hours, 12hours on days 1,2,4,6,8,10,12 and 14, once a day on days 15 to 19 in MAD

• Vital signs:Pulse rate

  Within 1 hour before administration, 1hour, 2hours, 4hours, 12hours, 24hours, 48hours, 72hours, 96hours, and 120hours after administration in SAD.

• Vital signs:Pulse rate

  Within 1 hour before administration, 1hours, 2hours, 4hours, 12hours on days 1,2,4,6,8,10,12 and 14, once a day on days 15 to 19 in MAD

• Vital signs:Respiratory rate

  Within 1 hour before administration, 1hour, 2hours, 4hours, 12hours, 24hours, 48hours, 72hours, 96hours, and 120hours after administration in SAD.

• Vital signs:Respiratory rate

  Within 1 hour before administration, 1hours, 2hours, 4hours, 12hours on days 1,2,4,6,8,10,12 and 14, once a day on days 15 to 19 in MAD

• Vital signs:Temperature

  Within 1 hour before administration,1hour, 2hours, 4hours, 12hours, 24hours, 48hours, 72hours, 96hours, and 120hours after administration in SAD.

• Vital signs:Temperature

  Within 1 hour before administration, 1hours, 2hours, 4hours, 12hours on days 1,2,4,6,8,10,12 and 14,once a day on days 15 to 19 in MAD

• Physical examination:General

  2hours, 24hours and 120hours after administration in SAD.

• Physical examination:General

  24hours after the first and last administration, prior to discharge from hospital in MAD

• Physical examination:Lymph node

  2hours, 24hours and 120hours after administration in SAD.

• Physical examination:Lymph node

  24hours after the first and last administration, prior to discharge from hospital in MAD

• Physical examination:Chest

  2hours, 24hours and 120hours after administration in SAD.

• Physical examination:Chest

  24hours after the first and last administration, prior to discharge from hospital in MAD

• Physical examination:Abdominal

  2hours, 24hours and 120hours after administration in SAD.

• Physical examination:Abdominal

  24hours after the first and last administration, prior to discharge from hospital in MAD

• 12-lead electrocardiogram (ECG) parameters ( Heart rate, PR, R-R, QRS and QTcF (average))

  Within 1 hour before administration,1hours, 2hours, 3hours, 24hours 120hours after administration in SAD.

Secondary Outcomes (20)

• SAD pharmacokinetic endpoint:The maximum plasma concentration (Cmax)

  Day1-Day6

• SAD pharmacokinetic endpoint:Time to Cmax (Tmax)

  Day1-Day6

• SAD pharmacokinetic endpoint:The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t)

  Day1-Day6

• SAD pharmacokinetic endpoint:The area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC0-∞)

  Day1-Day6

• SAD pharmacokinetic endpoint:Terminal rate constant (λz)

  Day1-Day6

Study Arms (4)

HS-10356 single dose

EXPERIMENTAL

Single oral dose of HS-10356 ascending dose

Drug: HS-10356

placebo single dose

PLACEBO COMPARATOR

Single oral dose of placebo ascending doses

Drug: Placebo

HS-10356 multiple doses

EXPERIMENTAL

Multiple oral doses of HS-10356 ascending doses

Drug: HS-10356

Placebo multiple doses

PLACEBO COMPARATOR

Multiple oral doses of placebo ascending doses

Drug: Placebo

Interventions

HS-10356 DRUG

Single dose of HS-10356

HS-10356 single dose

Placebo DRUG

Single dose of Placebo

placebo single dose

Eligibility Criteria

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

You may qualify if:

• Full understanding of the content, process and possible adverse reactions of the study, and sign the ICF voluntarily;
• Healthy Volunteers between 18 and 55 years of age (including the critical value);
• Male weight is not less than 50 kg, female weight is not less than 45 kg. The body mass index (BMI = weight (kg)/height (m2). The BMI should be controlled within the range of 18 to 26 (including the critical value);
• Volunteers agree to refrain from smoking, drinking alcohol. Avoid xanthine or caffeine (including chocolate, tea, coffee, cola, etc.) and avoid strenuous exercise;
• Agreed to use effective contraception from the date of signing of the ICF until six months after the last administration;
• The male volunteers agreed to refrain from donating sperm from the start of the drug until six months after they stopped the study;
• The female volunteers agreed to avoid ovum donation from the start of the drug until six months after they stopped the study;
• Pregnancy test results of female volunteers must be negative within 3 days of administration.

You may not qualify if:

• Pregnant and breastfeeding female.
• Volunteers with a history of cardiovascular, respiratory, liver, kidney, digestive tract, mental, neurological, hematological, metabolic and other systemic diseases, who are not suitable to participate in this study as assessed by the investigator.
• The results of vital signs, physical examination, laboratory examination and 12-lead ECG during screening were abnormal with clinical significance.
• Major surgery was performed within 3 months prior to the screening or surgery was planned during the study.
• Severe infections, such as cellulitis, pneumonia, sepsis, have occurred or are present in the 30 days prior to screening.
• ALT, AST, ALP or bilirubin were higher than the upper limit of normal.
• Creatinine clearance \< 90mL/min at screening (Cockcroft-Gault method), as follows:
• (140-age in years)×weight (kg)/72×serum creatinine（mg/dL）×(Female×0.85)；
• Hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), human immunodeficiency virus antibody (HIVAb) or syphilis antibody is positive.
• Volunteers had a history of drug dependence or abuse.
• A heavy smoker or smokers who smoked 5 or more cigarettes per day for 3 months prior to screening or tested positive for nicotine during screening.
• A history of alcohol abuse or a single consumption of more than 14 units of alcohol (1 unit = 285 mL of beer, 25 mL of spirits, 150 mL of wine) in the nearly two weeks prior to screening or a positive breath test for alcohol at screening.
• Participate in clinical trials of any drug or medical device within 3 months prior to screening.
• Blood donation or blood loss ≥ 400mL within 3 months prior to screening, or blood transfusion received; Blood donation or blood loss ≥ 200mL within 1 month before screening.
• Volunteers received systemic steroid, immunomodulator, or chemotherapy in the 3 months prior to screening，or likely to be treated with these drugs such as corticosteroids, immunoglobulin, and other immune or cytokine therapy during the study period.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

Location

Central Study Contacts

Xiaojian Zhang, BS

CONTACT

086-0371-66913047; Zhxj0524@sina.com

Xin Tian, PhD

CONTACT

086-0371-66295651; tianx@zzu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: December 3, 2020
• Study Start: December 1, 2020
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: December 3, 2020

Record last verified: 2020-11

Locations

CN (1)