A Study to Evaluate the Tolerability and Pharmacokinetics of Jiashen Tablets in Healthy Subjects

NCT04164290 | Completed Phase 1 DMC

• 1 other identifier: TSL-TCM-JSP-I
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Jiashen Tablets as an oral, compound traditional chinese medicine prepatations, have an effect on improvement of the heart failure. This study will assess the safety, tolerability and pharmacokinetics (PK) of Jiashen Tablets, following oral administration of single and multiple ascending dose of Jiashen Tablets.

Conditions

Healthy

Outcome Measures

Primary Outcomes (16)

• Number of participants with adverse events (AEs)

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants. Serious AEs will be recorded from the time of screening.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal blood pressure (BP)

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants. Blood pressure includes both systolic and diastolic BP.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal pulse

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal temperature

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal respiratory

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal findings in 12-lead safety Electrocardiogram (ECG)

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day-7) till follow-up visit (Up to 1 week)

• Number of participants with abnormal findings in 24h Holter

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day -1) till end of trial period

• Number of participants with abnormal physical examination findings

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. The complete physical examinations will include an assessment of the general appearance, skin, cardiovascular, abdomen, head, and neck, lymph nodes, musculoskeletal and neurological systems.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Hematology - absolute count of Red blood cell (RBC), White blood cell (WBC), Platelets

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Hematology-Hematocrit (HCT)

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb)

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Hematology-percentage of Basophils, Eosinophils, Monocytes, Neutrophils, Lymphocytes

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Clinical Chemistry- Liver function, Renal function, Electrolyte

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants. Liver function: Alanine aminotransferase, Aspartate aminotransferase,Alkaline phosphatase, Gamma-glutamyltransferase,Total Bilirubin, Direct Bilirubin. Renal function: Creatinine,Urea,β2-microglobulin. Electrolyte: Potassium,Sodium,Chloridion,Calcium.

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Urinalysis - Urine leukocyte, urine erythrocyte,specific grvity,Glucose, Protein, urobilinogen,bilirubin, ketone, bacteria

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: coagulation function -Prothrombin Time, Activated Partial Thromboplastin Time,Thrombin Time,Fibrinogen, International Normalized Ratio

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants

  From screening (Day -1) till follow-up visit (Up to 1 week)

• Number of participants with abnormal laboratory assessments: Fecal -Fecal Routine and Occult Blood

  To investigate the safety and tolerability of Jiashen Tablets following oral administration of single and multiple ascending doses at steady state in healthy participants

  From screening (Day -1) till follow-up visit (Up to 1 week)

Secondary Outcomes (9)

• Plasma PK analysis: Area under curve at steady state (AUCss)

  Day 1,7/8: Pre-dose and 0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,7.0,8.0,9.0,10,12,16,24,36,48 hours post-dose and Day 5-6/6-7: Pre-dose

• Plasma PK analysis: Maximum observed plasma concentration (Cmax)

  Day 1,7/8: Pre-dose and 0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,7.0,8.0,9.0,10,12,16,24,36,48 hours post-dose and Day 5-6/6-7: Pre-dose

• Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)

  Day 1,7/8: Pre-dose and 0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,7.0,8.0,9.0,10,12,16,24,36,48 hours post-dose and Day 5-6/6-7: Pre-dose

• Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

  Day 1,7/8: Pre-dose and 0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,7.0,8.0,9.0,10,12,16,24,36,48 hours post-dose and Day 5-6/6-7: Pre-dose

• Plasma PK analysis: Observed concentration at the end of the dosing interval following drug administration at steady state (Cssmin)

  Day 1,7/8: Pre-dose and 0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0,7.0,8.0,9.0,10,12,16,24,36,48 hours post-dose and Day 5-6/6-7: Pre-dose

Study Arms (12)

treatment group 1

ACTIVE COMPARATOR

Jiashen tablet, 0.47g, oral, once a day

Drug: Jiashen Tablets

treatment group 2

ACTIVE COMPARATOR

Jiashen tablet, 0.94g, oral, once a day

Drug: Jiashen Tablets

treatment group 3

ACTIVE COMPARATOR

Jiashen tablet,1.88g, oral, once a day

Drug: Jiashen Tablets

treatment group 4

ACTIVE COMPARATOR

Jiashen tablet,2.82g, oral, once a day

Drug: Jiashen Tablets

treatment group 5

ACTIVE COMPARATOR

Jiashen tablet,3.76g, oral, once a day

Drug: Jiashen Tablets

treatment group 6

ACTIVE COMPARATOR

Jiashen tablet,4.23g, oral, once a day

Drug: Jiashen Tablets

control group 1

PLACEBO COMPARATOR

Jiashen placebo tablet,0.47g, oral, once a day

Drug: Jiashen Tablets Placebo

control group 2

PLACEBO COMPARATOR

Jiashen placebo tablet,0.94g, oral, once a day

Drug: Jiashen Tablets Placebo

control group 3

PLACEBO COMPARATOR

Jiashen placebo tablet,1.88g, oral, once a day

Drug: Jiashen Tablets Placebo

control group 4

PLACEBO COMPARATOR

Jiashen placebo tablet,2.82g, oral, once a day

Drug: Jiashen Tablets Placebo

control group 5

PLACEBO COMPARATOR

Jiashen placebo tablet,3.76g, oral, once a day

Drug: Jiashen Tablets Placebo

control group 6

PLACEBO COMPARATOR

Jiashen placebo tablet,4.23g, oral, once a day

Drug: Jiashen Tablets Placebo

Interventions

Jiashen Tablets DRUG

1 tablet

Also known as: treatment group 1

treatment group 1

Jiashen Tablets Placebo DRUG

1 tablet

Also known as: control group 1

control group 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers, half male and half female, aged 18-50 years (including the boundary value), the age difference of the same batch of subjects should not exceed 10 years.
• Have a body mass index of all subjects between 19 and 24kg /m2 (inclusive) and weight of the male subject should be no less than 50Kg and the weight of the female subject should be no less than 45Kg.
• Passed the smoke test, alcohol and drug abuse test, general physical examination and laboratory examination, chest film, ultrasound, electrocardiogram and other physical and chemical tests.
• No history of major diseases, no history of smoking and drinking, negative blood pregnancy test of women of childbearing age and no lactation.
• Obtain informed consent and volunteer to be tested in accordance with the provisions of the Drug clinical trial quality management standard.

You may not qualify if:

• Have primary diseases of cardiovascular，hepatic or renal disease or any other condition. With history of digestive tract diseases, metabolic diseases, and neurological diseases.
• QTc extension (male \>430ms, female \>450ms).
• History of drug allergy or allergic constitution.
• Family history of hypokalemia, long QT syndrome or other TdP risk factors.
• Mentally or physically disabled.
• Any clinically significant abnormalities in physical examination, biochemical and hematuria routine examination, electrocardiogram, chest film and ultrasound examination,.
• Any positive result on Screening for serum hepatitis B tests (except surface antibodies), hepatitis C antibody , human immunodeficiency virus (HIV) and treponema pallidum antibody test.
• Those who had taken a drug known to damage an organ within 3 months, taken any drug within 2 weeks, and participated in other clinical trials within 4 weeks.
• Bleeding tendency.
• Women during menstruation, pregnancy and lactation.
• Abnormal vital signs (systolic pressure \<90mmHg or \>140mmHg, diastolic pressure \<60mmHg or \>90mmHg;Heart rate \<60bpm or \>100bpm).
• Have smoked more than one cigarette per day or used a considerable amount of nicotine products within the previous 3 months, and could not quit smoking during the experiment. Positive screen for the smoke test.
• Regular drinkers who drank more than 14 units of alcohol per week (1 unit =360mL beer or 45mL spirits with a 40% alcohol content or 150mL wine) during the 6 months prior to the trial, or who tested positive for alcohol, or who do not abstain during the trial.
• Excessive daily consumption of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250mL) or caffeine test positive.
• Have a history of blood transfusion or donation in the last 3 months (blood volume greater than 200mL).

Sponsors & Collaborators

• Tasly Pharmaceutical Group Co., Ltd: lead

Study Sites (1)

The second affiliated hospital of tianjin university of traditional Chinese medicine

Tianjin, Tianjin Municipality, China

Location

MeSH Terms

Interventions

jiashen

Study Officials

• Rui Liu

  Tasly Group, Co. Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A is double-blind with regard to treatment (Jiashen Tablets or placebo) at each dose level. Jiashen Tablets and placebo will be matched for formulation, appearance, and amount. Part B and Part C are open-label with regard to treatment (Jiashen Tablets) at each dose level.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 15, 2019
• Study Start: June 29, 2020
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: November 23, 2022

Record last verified: 2022-11

Locations

CN (1)