To Evaluate the Safety, Tolerability, and Pharmacokinetics Profiles of TG-1000 in Healthy Volunteers, and the Food Effect on Pharmacokinetics of Single Oral Dose of TG-1000 in Healthy Volunteers.

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 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.

Study Overview

• Status: Completed
• Conditions: Healthy Chinese Volunteers
• Intervention / Treatment: Drug: TG-1000; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing to provide written informed consent.
2. Age 18 (or legal adult age) to 45 years.
3. 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.
4. Subjects have good communication with Investigator and agree to follow the study requirement to complete study.

Exclusion Criteria:

1. Clinically significant abnormality in 12-lead ECG, chest X-ray, abdominal ultrasounds, physical examination, vital signs or laboratory values at Screening or Day-1.
2. Positive breath alcohol or urine drug tests at Day-1.
3. Positive test results for Immunoglobulin M anti-HAV antibody, HBsAg, anti-HCV antibody, HIV or syphilis at Screening.
4. Female subjects with positive pregnancy test results at Screening or Day-1.
5. Male subjects are unwilling to use effective contraception and refrain from sperm donation from Screening until 3 months after the study drug administration.

6. Current or prior history of any of the following:

   1. Significant cardiac disease, diabetes, liver, kidney disease, psychiatric diseases or drug abuse or diseases that will affect immunity.
   2. Difficulty in swallow or gastrointestinal disorder that could interfere with the absorption of the study drug
   3. Difficulty in blood sampling or venipuncture
   4. Drug allergy or hypersensitivity
   5. Blood donation ≥ 400 mL within 3 months before and after study.
   6. Alcoholics or frequent drinkers prior to Screening.
   7. Frequent smokers prior to Screening.

7. Use of any prohibited medications or surgeries prior to study drug administration:

   a. Received any other investigational agents or devices, liver enzyme inducer or inhibitors, medications including prescriptions, non-prescriptions or herbal remedies, dietary supplements or surgeries.

8. Unwilling to abstain from alcohol, tobacco, nicotine containing products, caffeine- or xanthine-containing beverages from Screening until discharge from the phase I unit.
9. Subjects may not be qualified for the study judged by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.; Drug: Placebo; Subjects will receive one single oral dose of placebo on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.; Drug: Placebo; Subjects will receive one single oral dose of placebo on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.; Drug: Placebo; Subjects will receive one single oral dose of placebo on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.; Drug: Placebo; Subjects will receive one single oral dose of placebo on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.; Drug: Placebo; Subjects will receive one single oral dose of placebo on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.
EXPERIMENTAL: 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.	Drug: TG-1000; Subjects will receive one single oral dose of TG-1000 on day 1 following protocol requirements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects of treatment-emergent adverse events	Any significant findings after dosing will be considered as adverse events.	8 days
Number of subjects of Significant Abnormal Vital Signs Findings	The systolic and diastolic blood pressure (mmHg), pulse/heart rate (beats/min), respiratory rate (breaths/min), and body temperature (oC) will be measured.	8 days
Number of subjects With Significant Abnormal Physical Examination Findings	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.	8 days.
Number of subjects With Significant Abnormal 12-lead Electrocardiography (ECG) Findings	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).	8 days
Number of subjects With Significant Abnormal Holter Electrocardiography (ECG) Findings	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.	12 hr pre-dose until 24 hr post-dose
Number of Participants With Significant Abnormal Laboratory Values	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	8 days
Peak Plasma Concentration (Cmax)	Blood sample will be collected to evaluate PK profile and food effect of TG-1000.	15 days
time to Cmax (Tmax)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
area under the curve from time zero to the time (AUC0-t)	Blood sample will be collected to evaluate PK profile and food effect of TG-1000.	15 days
area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
area under the concentration-time curve from time zero to infinity (AUC0-inf)	Blood sample will be collected to evaluate PK profile and food Effect of TG-1000.	15 days
terminal elimination half-life (T1/2, z)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
apparent total body clearance (CL/F)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
apparent total volume distribution (V/F)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
plasma concentration 24 h after dosing (C24)	Blood sample will be collected to evaluate PK profile of TG-1000.	15 days
urinary excretion ratio relative to dose from time zero to the time (Feu0-t)	Urine sample will be collected to evaluate PK profile of TG-1000.	15 days

Collaborators and Investigators

• Sponsor: TaiGen Biotechnology Co., Ltd.
• Collaborators: R&G Pharma Studies Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 17, 2020
• Primary Completion (ACTUAL): November 26, 2020
• Study Completion (ACTUAL): December 30, 2020

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (ACTUAL): July 31, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: TG-1000-C-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No