Pharmacokinetic and Tolerance Study of TQ-A3326 in Healthy Participants.

Pharmacokinetic and Tolerance Study in Healthy Participants: a Single-centre, Randomized, Double-blind, Placebo-controlled Trial

To study the single dose and multi-doses pharmacokinetic characteristics and tolerance of TQ-A3326 in the human body；To study the transformation of TQ-A3326；To study the effect of the food on the pharmacokinetic characteristics of TQ-A3326.

Study Overview

• Status: Unknown
• Conditions: Pharmacokinetic
• Intervention / Treatment: Drug: TQ-A3326; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410015
      • Recruiting
      • The Third Hospital of Changsha
      • Principal Investigator: Li Xin, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female, age 18 to 60 years, inclusive.
• The body weight of male is not less than 50kg, and female is not less than 45kg. All participants' body mass index (BMI) is between 19~26.
• Adequate blood cell counts, kidney function and liver function.
• Healthy participants should participate in the study voluntarily and sign informed consent.

Exclusion Criteria:

• Subjects with known allergy to the similar products tested.
• Subject is on a special diet (for example subject is vegetarian).
• Medical demographics with evidence of clinically significant deviation from normal medical condition.
• Female subjects who were pregnant or nursing.
• Results of laboratory tests which are clinically significant.
• Acute infection within one week preceding first study drug administration.
• History of drug or alcohol abuse.
• Subject does not agree not to take any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study.
• Subject does not agree not to consume any beverages or foods containing methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to the study administration of either study period until donating the last sample in each respective period.
• ale subjects (or their partner) or female subjects have the unprotective sex behavior or have a planned pregnancy during the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQ-A3326; TQ-A3326 (15mg-180mg: p.o. single dose; 60mg: p.o. multi-doses）	Drug: TQ-A3326; TQ-A3326 (15mg-180mg: p.o. single dose; 60mg: p.o. multi-doses）
Experimental: placebo; Placebo(15-180mg: p.o. single dose; 60mg: p.o. multi-doses)	Drug: placebo; Placebo(15-180mg: p.o. single dose; 60mg: p.o. multi-doses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs).	SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.	Day 1 up to Day 7 for non-SAEs .
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements.	Participants were assessed by investigator for any clinically significant changes in vital parameters like body temperature, respiratory rate, blood pressure, heart rate and weight. The assessment was performed by a calibrated sphygmomanometer and thermometer for blood pressure and temperature, respectively. Blood pressure and heart rate were measured after at least 5 minutes quiet seating of the subject. Weight was measured at the discharge. The criteria for clinically significant change was as per the investigators discretion.	Day 1 up to Day 7 or Discharge.
Number of Participants With Marked Abnormalities in Laboratory Findings.	Laboratory marked abnormalities were defined as Hematocrit (low) as <0.85*pre-treatment value, Leukocytes (low) as <0.9*lower limit of normal, Aspartate Aminotransferase (high) as >1.25*upper limit of normal, Creatinine (high) as >1.33*pre-treatment value, Bicarbonate (high) as >1.2*upper limit of normal, Total Protein (high) as >1.1*upper limit of normal, Creatinine Kinase (high) as >1.5*upper limit of normal, Blood in Urine (high) as ≥ 2*upper limit of normal. Participants were fasted for at least 10 hours prior to the collection of blood specimens for clinical laboratory tests.	Day 1 up to Day 7.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax).	Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay. 2）Grade 4 hematology toxicity	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-T]).	Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. It was calculated as the sum of linear trapezoids using non-compartmental analysis. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay.	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1.
Area Under the Plasma Concentration-time Curve From Time Zero (AUC[INF]) Extrapolated to Infinite Time.	Area under the plasma concentration-time curve from time zero extrapolated to infinite time was estimated as sum of AUC(0-T) and the extrapolated area, computed by the quotient of the last observable concentration and λ, where λ was the slopes of the terminal phases of the plasma concentration-time profiles. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay.	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1.
Time to Reach Maximum Plasma Concentration (Tmax).	Tmax was defined as the time required to reach maximum observed plasma concentration. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay.	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1.
Plasma Half-life (T-half)	Plasma half-life was defined as the time required for one half of the total amount of administered drug eliminated from the body. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay.	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1.
Apparent Total Body Clearance (CLT/F)	Apparent total body clearance (CLT/F) was calculated as Dose/AUC(INF), where CLT was the clearance of the drug and F was the absolute oral bioavailability. The plasma samples were analyzed for TQ-A3326 using a validated liquid chromatography-tandem mass spectrometric assay.	Pre-dose, 0.25hour, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour, 48hour, 72hour, 96hour, 120hour post-dosing on Day 1.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2018
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: May 28, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: ZDTQ-A3326-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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