To Evaluate PK and Safety Profile of Oral MAD of Separately Using TG-2349, DAG181 or Combination in Healthy Chinese Volunteers

July 26, 2018 updated by: Dongguan HEC TaiGen Biopharmaceuticals Co., Ltd.

A Single Center, Randomized, Open-label, Two-arm, Parallel Design Study to Evaluate PK and Safety Profile of Multiple Ascending Oral Doses of Separately Using TG-2349 or DAG181 or TG-2349 Plus DAG181 in Healthy Chinese Volunteers

To evaluate the drug-drug reactions between TG-2349 and DAG181, and the pharmacokinetics and tolerability profile in healthy Chinese volunteers to be the reference for protocol designs of subsequent clinical trials.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single center, randomized, open-label, two-arm, parallel design, phase I study that using TG-2349 or DAG181 alone, or TG-2349 plus DAG181 to evaluate the drug-drug reactions, the pharmacokinetics, and tolerability profile in healthy Chinese volunteers. The results will be the reference for protocol designs of subsequent clinical trials.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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 Institute 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 inclusive and male body weight ≥ 50 kg, female body weight ≥ 45 kg；
  4. In general good physical and mental health status on basis of 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: (a) Had undergone surgical sterilization, or (b) Subjects of childbearing potential must satisfy the following criteria: Before group assignment, the urine 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 Visit1 to Visit 2). Subject must also consent to keep the contraceptive method until 1 month after the study, and Breastfeeding is prohibited；
  6. Male 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 Visit1 to Visit 2) and within 1 month after the study；
  7. Have not used tobacco or nicotine-containing products within 1 month period to first dose of study drug；
  8. 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, refer to appendix 1) 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；筛选或研究第-1天时收缩压>140 mmHg或<90 mmHg、舒张压>90 mmHg、脉搏<50次/分或>100次/分；
  6. Any clinical significant abnormality on chest X-rays or abdominal ultrasound scan at screening (or within 2 weeks of signing the ICF)；
  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 dysphagia, 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 TG-2349 or its excipients, DAG181 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) drugs, 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, nutritional supplements, multi-vitamin, supplements for metals) within 7 days prior to the first dose of study drug；
  22. History of alcohol misuse (14 units alcohol/ week: 1 unit equal to bear 285 mL, spirits 25 mL, or wine 100 mL)；
  23. Blood donation ≥400 ml within 3 months prior to the first dose of study drug；
  24. Any disease or situation that would affect the safety of study drug or pharmacokinetics profile by Investigators' judgments；
  25. As determined by Investigator, a subject is not suitable to take part in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TG-2349 (400 mg) plus DAG181 (200 mg)
Dosing period 1 (Day 1 to 7): TG-2349 alone；Dosing period 2 (Day 8 to 14): TG-2349+DAG181
Drug: TG-2349 (400 mg) plus DAG181 (200 mg)
Dosing period 1 (Day 1 to 7): TG-2349 400 mg； Dosing period 2 (Day 8 to 14): TG-2349 400 mg + DAG181 200 mg
Experimental: DAG181 (200 mg) plus TG-2349 (400 mg)
Dosing period 1 (Day 1 to 7): DAG181 alone；Dosing period 2 (Day 8 to 14): TG-2349+DAG181
Drug: DAG181 (200 mg) plus TG-2349 (400 mg)
Dosing period 1 (Day 1 to 7): DAG181 200 mg； Dosing period 2 (Day 8 to 14): TG-2349 400 mg + DAG181 200 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cmax(ss)
Time Frame: 14 weeks
Maximum Plasma Concentration in a stable state
14 weeks
Ctrough(ss)
Time Frame: 14 weeks
Trough Plasma Concentration in a stable state
14 weeks
AUC(0-τ, ss)
Time Frame: 14 weeks
Area Under the Plasma Concentration vs. Time Curve
14 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: 14 weeks
Cmax: Maximum Plasma Concentration,
14 weeks
Ctrough
Time Frame: 14 weeks
Ctrough: Trough Plasma Concentration
14 weeks
Tmax
Time Frame: 14 weeks
Time at Which Maximum Plasma Concentration is Observed
14 weeks
AUC(0-24)
Time Frame: 14 weeks
AUC(0-24): Area Under the Plasma Concentration vs. Time Curve 0-24 hours
14 weeks
Tmax(ss)
Time Frame: 14 weeks
Tmax(ss): Time at Which Maximum Plasma Concentration is Observed in a stable state
14 weeks
λz
Time Frame: 14 weeks
λz: Terminal disposition rate constant/terminal rate constant
14 weeks
AUC(0-last)
Time Frame: 14 weeks
AUC(0-last): Area Under the Plasma Concentration vs. Time Curve 0 - the last dose
14 weeks
AUC(0-inf)
Time Frame: 14 weeks
AUC(0-inf): Area Under the Plasma Concentration vs. Time Curve 0 - infinity
14 weeks
MRT
Time Frame: 14 weeks
MRT: mean residence time
14 weeks
CL/F
Time Frame: 14 weeks
CL/F: total clearance rate
14 weeks
V/F
Time Frame: 14 weeks
V/F: apparent volume of distribution
14 weeks
DF
Time Frame: 14 weeks
DF=(Cmax - Ctrough) / (AUCss /τ)
14 weeks
12-lead ECG
Time Frame: 19 weeks
including heart rate, RR, PR, QRS, QT, QTc；
19 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 19 weeks
CTCAE v4.0
19 weeks
blood pressure (mmHg)
Time Frame: 19 weeks
Vital signs
19 weeks
pulse (beats/ min)
Time Frame: 19 weeks
Vital signs
19 weeks
respiratory rate (breaths/ min)
Time Frame: 19 weeks
Vital signs
19 weeks
body temperature (oC)
Time Frame: 19 weeks
Vital signs
19 weeks
General Appearance Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Skin Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Head and Neck Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Chest region Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Abdominal region Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Back region Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks
Extremities Physical examination
Time Frame: 19 weeks
Physical examination
19 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dongguan HEC TaiGen Biopharmaceuticals Co., Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
R&G Pharma Studies Co.,Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 5, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 5, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 24, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 1, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TGDAG-C-1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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