A Phase 1, Single-center, Randomized, Double-blind, Placebo-controlled, Single-dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics Profiles of TG-1000 in Healthy Volunteers, and to Evaluate the Food Effect on Pharmacokinetics of Single Oral Dose of TG-1000 in Healthy Volunteers.
Overview
- Phase
- Phase 1
- Intervention
- TG-1000
- Conditions
- Healthy Chinese Volunteers
- Sponsor
- TaiGen Biotechnology Co., Ltd.
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- area under the concentration-time curve from time zero to infinity (AUC0-inf)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics profiles of TG-1000 in healthy volunteers, and to evaluate the food effect on pharmacokinetics of single oral dose of TG-1000 in healthy volunteers.
Detailed Description
This is a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dose escalation study to evaluate the safety, tolerability, and pharmacokinetics profiles of TG-1000 in healthy volunteers, and to evaluate the food effect on pharmacokinetics of single oral dose of TG-1000 in healthy volunteers. The study will be divided into two parts. Part A is designed as randomized, double-blind, placebo-controlled, sequential, single ascending oral dose to evaluate the safety, tolerability, and PK profiles of TG-1000 in healthy volunteers. Part B is designed as randomized, open-label, two treatment (fasted vs. fed), two-period, two-sequence crossover to compare the effects of food on the Pharmacokinetic (PK) of single oral dose of TG-1000 in healthy subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to provide written informed consent.
- •Age 18 (or legal adult age) to 45 years.
- •Body mass index (BMI) in the range of ≥19.0 to ≤ 24.0 kg/m2 and body weight ≥ 50 kg for male and ≥ 45 kg for female at Screening.
- •Subjects have good communication with Investigator and agree to follow the study requirement to complete study.
Exclusion Criteria
- •Clinically significant abnormality in 12-lead ECG, chest X-ray, abdominal ultrasounds, physical examination, vital signs or laboratory values at Screening or Day-
- •Positive breath alcohol or urine drug tests at Day-
- •Positive test results for Immunoglobulin M anti-HAV antibody, HBsAg, anti-HCV antibody, HIV or syphilis at Screening.
- •Female subjects with positive pregnancy test results at Screening or Day-
- •Male subjects are unwilling to use effective contraception and refrain from sperm donation from Screening until 3 months after the study drug administration.
- •Current or prior history of any of the following:
- •Significant cardiac disease, diabetes, liver, kidney disease, psychiatric diseases or drug abuse or diseases that will affect immunity.
- •Difficulty in swallow or gastrointestinal disorder that could interfere with the absorption of the study drug
- •Difficulty in blood sampling or venipuncture
- •Drug allergy or hypersensitivity
Arms & Interventions
10 mg TG-1000
Eligible subjects will receive single oral dose of study drug (2 x 5-mg TG-1000 capsules)on Day 1 under fasted condition.
Intervention: TG-1000
20 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (20 mg TG-1000 capsule or Placebo capsule) on Day 1 under fasted condition.
Intervention: TG-1000
20 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (20 mg TG-1000 capsule or Placebo capsule) on Day 1 under fasted condition.
Intervention: Placebo
40 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (2 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: TG-1000
40 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (2 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: Placebo
80 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (4 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: TG-1000
80 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (4 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: Placebo
120 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (6 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: TG-1000
120 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (6 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: Placebo
160 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (8 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: TG-1000
160 mg TG-1000 or Placebo
Eligible subjects will receive single oral dose of study drug (8 x 20 mg TG-1000 capsules or Placebo capsules) on Day 1 under fasted condition.
Intervention: Placebo
X mg TG-1000 (fasted)+wash-out+X mg TG-1000 (fed)
Based on the preliminary results, one optimal dose (X mg) of TG-1000 will be selected. Subject will receive a single oral dose of TG-1000 under fasted condition. After washout period, subject will receive a single oral dose of TG-1000 under fed condition.
Intervention: TG-1000
X mg TG-1000 (fed)+wash-out+X mg TG-1000 (fasted)
Based on the preliminary results, one optimal dose (X mg) of TG-1000 will be selected. Subject will receive a single oral dose of TG-1000 under fed condition. After washout period, subject will receive a single oral dose of TG-1000 under fasted condition.
Intervention: TG-1000
Outcomes
Primary Outcomes
area under the concentration-time curve from time zero to infinity (AUC0-inf)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile and food Effect of TG-1000.
Number of subjects With Significant Abnormal Holter Electrocardiography (ECG) Findings
Time Frame: 12 hr pre-dose until 24 hr post-dose
Holter ECG will be monitor continue from 12 hr pre-dose until 24 hr post-dose. The Investigator will determine whether the results of the Holter monitoring are normal or abnormal.
area under the curve from time zero to the time (AUC0-t)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile and food effect of TG-1000.
Number of subjects With Significant Abnormal Physical Examination Findings
Time Frame: 8 days.
A full general physical examination of the major body systems (General Appearance; Dermatological including skin and nails; Head and Neck; Chest region including Heart and Lung; Abdominal region including Gastrointestinal and Gastroenterology; Back region; Extremities; Psychiatric or Neurological; Lymph nodes; Other) will be performed by investigator.
Number of subjects With Significant Abnormal 12-lead Electrocardiography (ECG) Findings
Time Frame: 8 days
12-lead ECG will be performed after a rest in a supine position. The following ECG parameters will be listed: heart rate, the time between QRS complexes (RR Interval) (ms), the beginning of the P wave to the first deflection of the QRS complex (PR Interval) (ms), first deflection of QRS complex to end of QRS complex at isoelectric line (QRS duration) (ms), first deflection of QRS complex to end of T wave at isoelectric line (QT interval) (ms), Corrected QT interval by Bazett (QTcB) (ms), and Corrected QT interval by - Fridericia (QTcF) (ms).
Number of subjects of treatment-emergent adverse events
Time Frame: 8 days
Any significant findings after dosing will be considered as adverse events.
Number of subjects of Significant Abnormal Vital Signs Findings
Time Frame: 8 days
The systolic and diastolic blood pressure (mmHg), pulse/heart rate (beats/min), respiratory rate (breaths/min), and body temperature (oC) will be measured.
Number of Participants With Significant Abnormal Laboratory Values
Time Frame: 8 days
Chemistry, Hematology, Coagulation, Urinalysis, Human Immunodeficiency Virus (HIV) test, Hepatitis A virus(HAV) test, Hepatitis B virus (HBV) test, Hepatitis C virus (HCV) test, syphilis, serum pregnancy tests and Breath Alcohol Test
time to Cmax (Tmax)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
Peak Plasma Concentration (Cmax)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile and food effect of TG-1000.
area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
apparent total volume distribution (V/F)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
terminal elimination half-life (T1/2, z)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
apparent total body clearance (CL/F)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
plasma concentration 24 h after dosing (C24)
Time Frame: 15 days
Blood sample will be collected to evaluate PK profile of TG-1000.
urinary excretion ratio relative to dose from time zero to the time (Feu0-t)
Time Frame: 15 days
Urine sample will be collected to evaluate PK profile of TG-1000.