A Clinical Trial of Safety and Tolerance of TQH3821 Tablets in Adult Healthy Subjects

A Randomized, Double-blind, Placebo-controlled Phase I Clinical Trial of TQH3821 in Adult Healthy Subjects

This study was a randomized, double-blind, placebo-controlled phase I clinical trial of TQH3821 in adult healthy subjects, which plans to recruit 72 healthy subjects.

The main purpose was to evaluate the safety and tolerance of different doses of TQH3821 or in combination with methotrexate tablets after single and multiple administration in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: TQH3821 tablets; Drug: TQH3821 tablets (Placebo); Drug: Methotrexate tablets

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266003
      • The Affiliated Hospital of Qingdao University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1 Sign an informed consent form before the test, and fully understand the content, process and possible adverse reactions of the test;
• 2 Be able to complete the research according to the requirements of the plan;
• 3 Subjects (including partners) are willing to voluntarily take effective contraception within 6 months from screening to the last study drug administration;
• 4 Male and female subjects aged 18 to 55 years (including critical value);
• 5 Male subjects weigh not less than 50 kg, female subjects weigh not less than 45 kg, BMI in the range of 18 ~ 28 kg / m2 (including critical value);
• 6 Physical examination, normal or abnormal vital signs are of no clinical significance

Exclusion Criteria:

• 1 Those who smoke more than 5 cigarettes per day in the 12 weeks before screening;
• 2 Allergic constitution (a variety of drug and food allergies);
• 3 Have a history of substance abuse, drug and/or alcohol abuse;
• 4 Donate blood or lose a lot of blood (> 450 mL) within 12 weeks prior to screening;
• 5 Take any drug that alters the activity of liver enzymes 28 days before screening, or combined with inhibitors or inducers of Cytochrome P4503A4 enzyme (CYP3A4 );
• 6 Took any prescription drugs, over-the-counter drugs, any vitamin products or herbs within 14 days prior to screening;
• 7 Those who have taken a special diet or have strenuous exercise within 2 weeks before screening, or other factors that affect drug absorption, distribution, metabolism, excretion and other factors;
• 8 Those who are vaccinated with live attenuated vaccines within 28 days before the start of research treatment, inactivated vaccines within 7 days, or vaccinated during the study period;
• 9 Have taken research drugs within 12 weeks before taking our research drugs, or participated in clinical trials of drugs;
• 10 Have a history of dysphagia or any gastrointestinal diseases that affect the absorption of the drug or a history of gallbladder resection or biliary tract diseases;
• 11 Have any disease that increases the risk of bleeding, such as hemorrhoids, acute gastritis or stomach and duodenal ulcers;
• 12 Subjects who could not tolerate a standard meal; (only applies to subjects participating in the postprandial test);
• 13 Electrocardiogram (ECG) abnormalities have clinical significance;
• 14 Female subjects are breastfeeding during the screening period or during the test or have a positive serum pregnancy result;
• 15 Diseases with abnormal clinical significance in clinical laboratory examination or other clinical findings within 24 weeks before screening;
• 16 Positive screening for viral hepatitis (including hepatitis B and C), Acquired Immune Deficiency Syndrome (AIDS) antibodies, treponemal antibodies;
• 17 Acute illness or concomitant medication from the screening stage to the study of medication;
• 18 Chocolate, any caffeinated or xanthine-rich foods or beverages taken 24 hours before taking the study drug;
• 19 Have taken any products containing alcohol within 24 hours before taking the research medication;
• 20 Positive for urine drug screening;
• 21 Participants who were considered by the investigators to have other factors that were not suitable for this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQH3821 Tablets (Food Effect); TQH3821 tablets, 2 sequential periods (fasting and fed)	Drug: TQH3821 tablets; TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.
Experimental: TQH3821 Tablets (Single Administration Dose); TQH3821 tablets, Single administration	Drug: TQH3821 tablets; TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.
Placebo Comparator: TQH3821 Placebo Tablets (Single Administration Dose); TQH3821 placebo tablets, Single administration	Drug: TQH3821 tablets (Placebo); TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.
Placebo Comparator: TQH3821 Placebo Tablets (Food Effect); TQH3821 placebo tablets, 2 sequential periods (fasting and fed)	Drug: TQH3821 tablets (Placebo); TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.
Experimental: TQH3821 Tablets (Multiple Administration Dose); TQH3821 tablets once every 12 hours for 7 times during the continuous administration phase.	Drug: TQH3821 tablets; TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.
Placebo Comparator: TQH3821 Placebo Tablets (Multiple Administration Dose); TQH3821 placebo tablets once every 12 hours for 7 times during the continuous administration phase.	Drug: TQH3821 tablets (Placebo); TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.
Experimental: TQH3821 Tablets + Methotrexate Tablets; Take Methotrexate Tablets once in the first cycle, take TQH3821 Tablets once every 12 hours in the second cycle for 6 times, and then TQH3821 Tablets + Methotrexate Tablets once in the third cycle.	Drug: TQH3821 tablets; TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.; Drug: Methotrexate tablets; Methotrexate tablets is a folic acid antagonist, which belongs to an anti-rheumatic drug to improve the condition
Placebo Comparator: TQH3821 Placebo Tablets + Methotrexate Tablets; Take Methotrexate Tablets once in the first cycle, take TQH3821 placebo tablets once every 12 hours in the second cycle for 6 times, and then TQH3821 placebo tablets + Methotrexate Tablets once in the third cycle.	Drug: TQH3821 tablets (Placebo); TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.; Drug: Methotrexate tablets; Methotrexate tablets is a folic acid antagonist, which belongs to an anti-rheumatic drug to improve the condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Safety and tolerability are assessed by the incidence of adverse events and its severity caused by the study drug during or after dose.	The first day of the first administration until 8 days after the last administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak concentration (Cmax)	Peak concentration (Cmax) refers to the highest blood drug concentration achieved after administration called blood drug peak concentration (referred to as peak concentration), which is related to the dose administered, the route of administration, the number of times of administration and the time of arrival	Pharmacokinetics blood samples were collected from 60 minutes before administration on Day 1 to 168 hours after the last administration.
Plasma concentration-area under time curve (AUC0-t)	The area under the plasma concentration-time curve from the beginning of the first administration to the last measurable concentration point	Pharmacokinetics blood samples were collected from 60 minutes before administration on Day 1 to 168 hours after the last administration.
Plasma concentration-area under time curve (AUC0-∞)	Extrapolated from the first administration to the area under the plasma concentration-time curve to infinity	Pharmacokinetics blood samples were collected from 60 minutes before administration on Day 1 to 168 hours after the last administration.
High sensitivity C-reactive protein (hs-CRP)	Hypersensitive C-reactive protein is a kind of C-reactive protein in plasma. It is a non-specific marker of acute systemic inflammatory response synthesized by the liver	Multiple Administration Dose: Blood samples were collected from 60 minutes before administration on Day 1 to 192 hours after the consecutive administration.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2022
• Primary Completion (Actual): May 20, 2023
• Study Completion (Actual): May 20, 2023

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: TQH3821-I-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