A Randomized, Double-Blind, Placebo Controlled, Phase I Study to Assess, Safety, Tolerability, Pharmacokinetics of HS-10383 Administered Orally in China Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- HS-10383
- Conditions
- Cough
- Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability Evaluation
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a first-in-human study that will investigate the safety, tolerability and pharmacokinetics of ascending single doses of HS-10383 using a randomized, double blind, placebo controlled, single center study design.
Participants in this study will receive either the study drug or placebo tablets (a placebo looks like the test drug but does not have any medicine in it). The dosage will be one single dose of study drug/placebo received on only one day. The total study duration for each participant will be usually no more than 10 days. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
Detailed Description
HS-10383 is a selective P2X3 receptor antagonist being developed for the treatment of refractory/unexplained chronic cough. This Phase 1 study will investigate the safety, tolerability and pharmacokinetics of ascending single doses of HS-10383 administered orally to healthy volunteers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy participants aged from 18 to 45 years ;
- •Subjects need to fully understand the research content and process, as well as possible adverse reactions, and voluntarily sign the informed consent;
- •Male weight ≥ 50kg, female weight ≥ 45kg, body mass index {BMI, BMI=weight/height 2 (kg/m2)} is controlled within the range of 18\~26 (including the critical value);
- •Subjects need to agree to take effective contraceptive methods from the screening date to 90 days after the last dose;
- •Male subjects must agree not to donate sperm within 90 days from the start of the administration to the last administration.
Exclusion Criteria
- •The following medical histories, such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system and tumor, etc., were screened. evaluated as unsuitable to participate in this study;
- •Any known presence or history of hypogeusia, abnormal taste or dysgeusia;
- •Any known presence or history of severe allergies, or known to be allergic to the components of the test drug;
- •Use of any drugs, including prescription drugs, over-the-counter drugs or herbal preparations, cannot be avoided or expected to start 2 weeks (or 5 half-lives) before screening and throughout the study period;
- •Any findings of electrocardiogram outside from normal, such as the QT interval (QTcF) corrected by the Fridericia formula, the absolute value of QTcF for males is \>450 ms, and the absolute value of QTcF for females is \>470 ms;
- •Any findings of blood pressure or pulse in resting state outside from normal a: such as systolic blood pressure \<90 mmHg or ≥140 mmHg, diastolic blood pressure \<60 mmHg or ≥90 mmHg, pulse \<55 bpm or \>100 bpm;
- •Serum creatinine exceeds the upper limit of normal (ULN) at screening;
- •Infectious diseases with hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody test were positive at the time of screening;
- •Any findings from the medical examination (comprehensive physical examination, vital signs, blood oxygen saturation, laboratory tests, abdominal B-ultrasound and chest X-ray ) outside from normal and deemed by the investigator to be clinically significant;
- •Drug abusers, or have used soft drugs (such as marijuana) within 3 months prior to screening, or have taken hard drugs (such as cocaine, phencyclidine, etc.) within 1 year before screening;
Arms & Interventions
HS-10383
HS-10383 was administered at 8 am on the first day, 4 dose levels
Intervention: HS-10383
HS-10383 Placebo
Matching placebo to HS-10383 was administered at 8 am on the first day, 4 dose levels
Intervention: HS-10383 Placebo
Outcomes
Primary Outcomes
Safety and Tolerability Evaluation
Time Frame: up to 9 days
1. Adverse events (AEs), serious adverse events (SAEs) and adverse events leading to withdrawal from the study, the incidence, severity and correlation with the trial drug; 2. Changes in laboratory tests (blood routine, urine routine, blood biochemistry and coagulation function) before and after administration; 3. Changes in vital signs (respiration, pulse, blood pressure and body temperature) and SpO2 before and after administration; 4. Electrocardiogram (ECG) to check the changes before and after administration.
Secondary Outcomes
- Area Under the Concentration-time Curve0-∞(up to 9 days)
- Clearance Rate(up to 9 days)
- Apparent Volume of Distribution(up to 9 days)
- Mean Retention Time(up to 9 days)
- Maximum plasma concentration (Cmax)(up to 9 days)
- Time of Maximum Concentration(up to 9 days)
- Terminal Rate Constant(up to 9 days)
- Area Under the Concentration-time Curve0-t(up to 9 days)
- Elimination Halflife(up to 9 days)