To Evaluate the Safety, Tolerability, and Pharmacokinetics Profile in Healthy Chinese Volunteers of TG-2349

A Phase I, Randomized, Double-blind, Placebo Controlled, Ascending Dose Study in Healthy Chinese Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) Profile of Single and Multiple Ascending Oral Doses of TG-2349

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of different doses of TG-2349 (Furaprevir capsule) in healthy Chinese volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Chinese Volunteers
• Intervention / Treatment: Drug: Furaprevir capsule (SAD); Drug: Placebo (SAD); Drug: Furaprevir capsule (MAD); Drug: Placebo (MAD)

Detailed Description

This study is to evaluate the safety, tolerability, and pharmacokinetics (PK) profile in healthy Chinese volunteers with single or multiple ascending oral doses of TG-2349 (Furaprevir capsule). The study is separated into two parts, part A and part B.

Part A：To evaluate the safety, tolerability, and PK profile of single ascending oral dose (100 mg, 200 mg, 400 mg, and 600 mg) of TG-2349 in healthy Chinese volunteers.

Part B：To evaluate the safety, tolerability, and PK profile of multiple ascending oral doses (200 mg, 400 mg, and 600 mg) of TG-2349 for five days in healthy Chinese volunteers.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Before starting the study, an informed consent form (ICF) approved by the Institutional Review Board (IRB) is obtained from the subject or his/her legal representative；
2. Male or female, and 18 to 45 years of age inclusive when signing ICF；
3. Body mass index (BMI) in the range of 19.0 to 24.0 kg/m2 and male body weight ≥ 50 kg, female body weight ≥ 45 kg；
4. In generally good physical and mental health status on basis of a medical history review, physical examination and vital signs, 12-lead ECG, and laboratory results at screening；

5. For females, one of the following criteria must be fulfilled

   1. Had undergone surgical sterilization, or
   2. Subjects of childbearing potential must satisfy the following criteria:

   Before group assignment, the pregnancy test is negative, and Subjects agree to use an approved contraceptive method (i.e. oral spermicidal agent, condoms, or intrauterine devices) during the entire study period (from signing ICF to the last visit). Subjects must also consent to keep the contraceptive method unchanged until 1 month after the study, and Breastfeeding is prohibited

6. Males must be willing to use a reliable form of contraception (use of a condom or spouses using any of the above standards) during the entire study period (from signing ICF to the last visit)；
7. Have not used tobacco or nicotine-containing products within 1 month prior to the first dose of study drug；
8. Have not drunk alcohol beverages or drank alcoholic beverages less than 12 times within 3 months prior to the first dose of study drug；
9. Willing to abstain from caffeine- or xanthine-containing beverages, including coffee and tea, chocolate, alcohol, grapefruit juice, and Seville oranges juice before 24 hr and during the Stay-on Site period.

Exclusion Criteria:

1. Current, prior history, or family history of any disease of sudden cardiac death, myocardial ischemia, myocardial infarction, congestive heart failure, QT prolongation syndrome, hypokalemia, myocarditis, exertional dyspnea, cerebrovascular injury, venous thromboembolism；
2. Requires concomitant medication associated with increased QTc interval (i.e. Class I or III antiarrhythmic agents or with cardiac insufficiency；
3. Any abnormality on 12-lead ECG: PR>240 ms, PR<110 ms, QRS>110 ms, QTc>450 ms, or bradycardia ( heart rate < 50 beats/min) at screening or the day -1；
4. Any clinical significant abnormality on 12-lead ECG (i.e. atrioventricular block, TdT, other types of ventricular tachycardia, atrial fibrillation and ventricular flutter, clinical significant abnormality on T wave changes or any abnormality on 12-lead ECG that effects QTc intervals) at screening or the day -1；
5. Systolic pressure>140 mmHg or <90 mmHg, diastolic pressure >90 mmHg, pulse <50 beats/min or >100 beats/min at screening or the day -1；
6. Any clinical significant abnormality on chest X-rays or abdominal ultrasound scan at screening；
7. Positive serological test for hepatitis A (IgM anti-HAV), hepatitis B (HbsAg), hepatitis C (anti-HCV antibody), or syphilis at screening；
8. Pregnant or breastfeeding；
9. Any abnormal laboratory values (normal value ±10％) that are considered clinical significant by the Investigator at screening or the day -1；
10. Positive breath alcohol test or urine drug screen at screening or the day -1；
11. Current or prior history of any disease of diabetes, cardiovascular, hepatic or renal impairment；
12. Any malabsorption syndrome or other gastrointestinal disturbances affecting drug absorption；
13. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy；
14. History of epileptic seizure, mental disorders affecting the subject's compliance with the protocol, suicidal risk, or a history of alcohol or illicit drug abuse；
15. Currently has any disease that seriously affects the immune system, for instance, human immunodeficiency virus (HIV) infection, hematological malignancy, solid cancer or splenectomy；
16. Allergy, hypersensitivity or allergic reaction to Furaprevir or its excipients, or Sulfonamides；
17. History of surgery within 6 months prior to the first dose of study drug；
18. Received any hepatic enzyme inducers or hepatic enzyme inhibitors within 30 days prior to the first dose of study drug through medical history questionnaire (refer to appendix 2)；
19. Received any investigational drugs within 3 months prior to the first dose of study drug；
20. Received any prescription drugs, over-the-counter (OTC) drug, or Chinese herbal medicines within 14 days prior to the first dose of study drug；
21. Received any nutritional supplies, including multivalent cations products (i.e. Ca-, Al-, Mg-, Fe-, and Zn-containing products, sucralfate, antacid, nutritional supplements, multi-vitamin, supplements for metals) within 7 days prior to the first dose of study drug；
22. Blood donation ≥400 ml within 3 months prior to the first dose of study drug；
23. Any disease or situation that would affect the safety of study drug or pharmacokinetics profile by Investigators' judgments；
24. As determined by Investigator, a subject is not suitable to take part in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furaprevir capsule (SAD); single ascending oral dose (100 mg, 200 mg, 400 mg, and 600 mg) of TG-2349 (Furaprevir capsule)	Drug: Furaprevir capsule (SAD); There are four doses in this part, 100 mg, 200 mg, 400 mg, and 600 mg. Each subject will receive the sample once by oral administration.; Other Names: TG-2349 (SAD)
Placebo Comparator: Placebo (SAD); Single ascending oral dose of Furaprevir similar capsule. .	Drug: Placebo (SAD); Each subject will receive the sample once by oral administration.
Experimental: Furaprevir capsule (MAD); multiple ascending oral doses (200 mg, 400 mg, and 600 mg) of TG-2349 (Furaprevir capsule)	Drug: Furaprevir capsule (MAD); There are three doses in this part, 200 mg, 400 mg, and 600 mg. Each subject will be allocated into one dosing regimen and receive the sample once daily for 5 consecutive days by oral administration.; Other Names: TG-2349 (MAD)
Placebo Comparator: Placebo (MAD); Multiple ascending oral doses of Furaprevir similar capsule	Drug: Placebo (MAD); Each subject will be allocated into one dosing regimen and receive the sample once daily for 5 consecutive days by oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Maximum Plasma Concentration)	Maximum Plasma Concentration	10 days
Tmax (Time at Which Maximum Plasma Concentration is Observed)	Time at Which Maximum Plasma Concentration is Observed	10 days
AUC (Area Under the Plasma Concentration)	Area Under the Plasma Concentration	10 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	CTCAE v4.0	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-lead ECG (electrocardiogram)		10 days
blood pressure (mmHg)	Vital signs	10 days
pulse (beats/ min)	Vital signs	10 days
respiratory rate (breaths/ min)	Vital signs	10 days
body temperature (oC)	Vital signs	10 days
General Appearance Physical examination	Physical examination	10 days
Skin Physical examination	Physical examination	10 days
Head and Neck Physical examination	Physical examination	10 days
Chest region Physical examination	Physical examination	10 days
Abdominal region Physical examination	Physical examination	10 days
Back region Physical examination	Physical examination	10 days
Extremities Physical examination	Physical examination	10 days

Collaborators and Investigators

• Sponsor: Dongguan HEC TaiGen Biopharmaceuticals Co., Ltd.
• Collaborators: R&G Pharma Studies Co.,Ltd.
• Investigators: Principal Investigator: Pingsheng Xu, PhD, Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: May 6, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: tolerability; safety; PK; single ascending oral dose; multiple ascending oral doses
• Other Study ID Numbers: TG-2349-C-01

Drug and device information, study documents

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