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

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics of Jiashen Tablets in Healthy Subjects

Patrocinadores

Patrocinador principal: Tasly Pharmaceuticals, Inc.

Fuente Tasly Pharmaceuticals, Inc.
Resumen breve

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.

Descripción detallada

This study will include a randomized, double-blind, placebo-controlled, single ascending dose design study (Part A), and an open-label SDAD pre-multiple daily ascending dose (MDAD) study (Part B) and an open-label MDAD study (Part C) study.

The study will be conducted in healthy participants and performed at a single study center. 70 healthy participants are planned to be included in the study.

Part A will include six cohorts, 40 participants. Within each cohort, 2 participants will be randomized to receive placebo and other participants randomized to receive Jiashen Tablets. Each participant will receive Jiashen Tablets at the selected dose level or placebo by oral administration in a fasted state once daily.

Part B will include two cohorts, 12 participants, minimum dose group and maximum dose group respectively depending on the findings. Within each cohort, participant will receive Jiashen Tablets at the selected dose level by oral administration in a fasted state once daily.

Part C will include three cohorts, 24 participants. Within each cohort, participant will receive Jiashen Tablets at the selected dose level by oral administration in a fasted state once daily for 7 days.

Estado general Not yet recruiting
Fecha de inicio January 2020
Fecha de Terminación December 2020
Fecha de finalización primaria December 2020
Fase Phase 1
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Number of participants with adverse events (AEs) From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal blood pressure (BP) From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal pulse From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal temperature From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal respiratory From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal findings in 12-lead safety Electrocardiogram (ECG) From screening (Day-7) till follow-up visit (Up to 1 week)
Number of participants with abnormal findings in 24h Holter From screening (Day -1) till end of trial period
Number of participants with abnormal physical examination findings 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 From screening (Day -1) till follow-up visit (Up to 1 week)
Number of participants with abnormal laboratory assessments: Hematology-Hematocrit (HCT) From screening (Day -1) till follow-up visit (Up to 1 week)
Number of participants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb) 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 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 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 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 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 From screening (Day -1) till follow-up visit (Up to 1 week)
Resultado secundario
Medida Periodo de tiempo
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
Plasma PK analysis: Elimination half-life(t1/2) 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 at steady state (Cmax,ss), time to reach peak or maximum observed concentration following drug administration at steady state (tmax,ss) 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: Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve following drug administration (λz) 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: Terminal half-life, estimated as (ln2)/λz (t½λz) 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
Inscripción 70
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 1 tablet

Etiqueta de grupo de brazo: treatment group 1

Otro nombre: treatment group 1

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 2 tablets

Etiqueta de grupo de brazo: treatment group 2

Otro nombre: treatment group 2

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 4 tablets

Etiqueta de grupo de brazo: treatment group 3

Otro nombre: treatment group 3

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 6 tablets

Etiqueta de grupo de brazo: treatment group 4

Otro nombre: treatment group 4

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 8 tablets

Etiqueta de grupo de brazo: treatment group 5

Otro nombre: treatment group 5

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets

Descripción: 9 tablets

Etiqueta de grupo de brazo: treatment group 6

Otro nombre: treatment group 6

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 1 tablet

Etiqueta de grupo de brazo: control group 1

Otro nombre: control group 1

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 2 tablets

Etiqueta de grupo de brazo: control group 2

Otro nombre: control group 2

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 4 tablets

Etiqueta de grupo de brazo: control group 3

Otro nombre: control group 3

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 6 tablets

Etiqueta de grupo de brazo: control group 4

Otro nombre: control group 4

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 8 tablets

Etiqueta de grupo de brazo: control group 5

Otro nombre: control group 5

Tipo de intervención: Drug

Nombre de intervención: Jiashen Tablets Placebo

Descripción: 9 tablets

Etiqueta de grupo de brazo: control group 6

Otro nombre: control group 6

Elegibilidad

Criterios:

Inclusion Criteria:

1. 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.

2. 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.

3. 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.

4. No history of major diseases, no history of smoking and drinking, negative blood pregnancy test of women of childbearing age and no lactation.

5. Obtain informed consent and volunteer to be tested in accordance with the provisions of the Drug clinical trial quality management standard.

Exclusion Criteria:

1. Have primary diseases of cardiovascular,hepatic or renal disease or any other condition. With history of digestive tract diseases, metabolic diseases, and neurological diseases.

2. QTc extension (male >430ms, female >450ms).

3. History of drug allergy or allergic constitution.

4. Family history of hypokalemia, long QT syndrome or other TdP risk factors.

5. Mentally or physically disabled.

6. Any clinically significant abnormalities in physical examination, biochemical and hematuria routine examination, electrocardiogram, chest film and ultrasound examination,.

7. 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.

8. 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.

9. Bleeding tendency.

10. Women during menstruation, pregnancy and lactation.

11. Abnormal vital signs (systolic pressure <90mmHg or >140mmHg, diastolic pressure <60mmHg or >90mmHg;Heart rate <60bpm or >100bpm).

12. 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.

13. 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.

14. Excessive daily consumption of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250mL) or caffeine test positive.

15. Have a history of blood transfusion or donation in the last 3 months (blood volume greater than 200mL).

16. Have a history of drug abuse and tested positive for drug abuse (morphine, methamphetamine, ketamine, dimethyldimethamphetamine, THC, cocaine).

17. Judgment by the Investigator that the participant should not participate in the study (such as weak, etc).

Género: All

Edad mínima: 18 Years

Edad máxima: 50 Years

Voluntarios Saludables: Accepts Healthy Volunteers

Oficial general
Apellido Papel Afiliación
Rui Liu Study Director Tasly Group, Co. Ltd.
Contacto general

Apellido: Rui Liu

Teléfono: 022-86343626

Email: [email protected]

Ubicación
Instalaciones: Contacto: The second affiliated hospital of tianjin university of traditional Chinese medicine Yuhong Huang 022-60637023
Ubicacion Paises

China

Fecha de verificación

November 2019

Fiesta responsable

Tipo: Sponsor

Tiene acceso ampliado No
Número de brazos 12
Grupo de brazo

Etiqueta: treatment group 1

Tipo: Active Comparator

Descripción: Jiashen tablet, 0.47g, oral, once a day

Etiqueta: treatment group 2

Tipo: Active Comparator

Descripción: Jiashen tablet, 0.94g, oral, once a day

Etiqueta: treatment group 3

Tipo: Active Comparator

Descripción: Jiashen tablet,1.88g, oral, once a day

Etiqueta: treatment group 4

Tipo: Active Comparator

Descripción: Jiashen tablet,2.82g, oral, once a day

Etiqueta: treatment group 5

Tipo: Active Comparator

Descripción: Jiashen tablet,3.76g, oral, once a day

Etiqueta: treatment group 6

Tipo: Active Comparator

Descripción: Jiashen tablet,4.23g, oral, once a day

Etiqueta: control group 1

Tipo: Placebo Comparator

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

Etiqueta: control group 2

Tipo: Placebo Comparator

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

Etiqueta: control group 3

Tipo: Placebo Comparator

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

Etiqueta: control group 4

Tipo: Placebo Comparator

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

Etiqueta: control group 5

Tipo: Placebo Comparator

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

Etiqueta: control group 6

Tipo: Placebo Comparator

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

Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Descripción del modelo de intervención: test group1 1 tablet test group2 2 tablets test group3 4 tablets test group4 6 tablets test group5 8 tablets test group6 9 tablets placebo group1 1 tablet placebo group2 2 tablets placebo group3 4 tablets placebo group4 6 tablets placebo group5 8 tablets placebo group6 9 tablets

Propósito primario: Treatment

Enmascaramiento: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Descripción de enmascaramiento: 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.

Fuente: ClinicalTrials.gov