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

Study Overview
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Brief Summary
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This study was a randomized, double-blind, placebo-controlled phase I clinical trial of TQH3821 in adult healthy subjects, which plans to recruit 62 healthy subjects. The main purpose was to evaluate the safety and tolerance of TQH3821 in multiple doses, single and multiple times in healthy subjects and in combination with methotrexate tablets.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: TQH3821 tablets
* Drug: TQH3821 tablets (Placebo)
* Drug: Methotrexate tablets


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQH3821 Tablets (Single Administration Dose)<br>TQH3821 tablets，Single administration | Drug: TQH3821 tablets<br>* TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.<br>|
| Placebo Comparator: TQH3821 Tablets (Placebo) (Single Administration Dose)<br>TQH3821 Tablets (Placebo), Single administration | Drug: TQH3821 tablets (Placebo)<br>* TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.<br>|
| Experimental: TQH3821 Tablets (Food Effect)<br>TQH3821 tablets, 2 sequential periods (fasting and fed) | Drug: TQH3821 tablets<br>* TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.<br>|
| Placebo Comparator: TQH3821 Tablets (Placebo) (Food Effect)<br>TQH3821 Tablets (Placebo), 2 sequential periods (fasting and fed) | Drug: TQH3821 tablets (Placebo)<br>* TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.<br>|
| Experimental: TQH3821 Tablets (Multiple Administration Dose)<br>Take TQH3821 tablets 11 times | Drug: TQH3821 tablets<br>* TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.<br>|
| Placebo Comparator: TQH3821 Tablets (Placebo) (Multiple Administration Dose)<br>Take TQH3821 Tablets (Placebo) 11 times | Drug: TQH3821 tablets (Placebo)<br>* TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.<br>|
| Experimental: TQH3821 Tablets + Methotrexate Tablets<br>Take TQH3821 Tablets once in the first cycle, take Methotrexate Tablets once in the second cycle, and take TQH3821 Tablets + Methotrexate Tablets in the third cycle | Drug: TQH3821 tablets<br>* TQH3821 tablets is an Interleukin-1 receptor-associated kinase 4 inhibitor that exhibits a high degree of inhibitory activity against IRAK4 kinase.<br>Drug: Methotrexate tablets<br>* Methotrexate tablets is a folic acid antagonist, which belongs to an anti-rheumatic drug to improve the condition<br>|
| Placebo Comparator: TQH3821 Tablets (Placebo) + Methotrexate Tablets<br>Take TQH3821 Tablets (Placebo) once in the first cycle, take Methotrexate Tablets once in the second cycle, and take TQH3821 Tablets (Placebo) + Methotrexate Tablets in the third cycle | Drug: TQH3821 tablets (Placebo)<br>* TQH3821 tablets (Placebo) is a placebo produced with reference to TQH3821 tablets, which has no effect on IRAK4 kinase.<br>Drug: Methotrexate tablets<br>* Methotrexate tablets is a folic acid antagonist, which belongs to an anti-rheumatic drug to improve the condition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety and tolerability are assessed by observing adverse reactions or serious conditions caused by the drug during or after use. | 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 216 hours after administration on Day 9. |