Ascending Single-Dose and Multiple-Dose Study to Evaluate RJ4287 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
A Randomized Study of RJ4287 Drug to Evaluate the Safety, Tolerability, Pharmacokinetics and Food-effect of Single and Multiple Doses in Healthy Volunteers

Official Title
-----------------
A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food-effect of Single and Multiple Oral Doses of RJ4287 in Healthy Volunteers

Conditions
-----------------
Drug Safety

Intervention / Treatment
-----------------
* Drug: RJ4287
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and Female between 18 and 55 years old，inclusive Body weight >50 kg for Male and >45 kg for Female with a body mass index BMI between 19-28 kg/m2（inclusive） Female subjects of childbearing potential who have had no unprotected sex within 14 days prior to screening and who have had a negative pregnancy test during the screening period; subjects (including partners) who have no plans for pregnancy, sperm donation or egg donation and are willing to use effective contraception from the time of informed consent until 6 months after administration of the test product; The subject must be willing and able to provide written informed consent Exclusion Criteria: History of thyroid disorder or abnormal thyroid function tests at screening Abnormal abdominal ultrasound findings with clinical significance Subjects with any of the following laboratory tests at screening or baseline were not eligible for enrollment in this study: 1) Glutamic transaminase (AST), glutamic aminotransferase (ALT) or direct bilirubin above the upper limit of the reference range at screening; 2) Positive screening for HIV antibodies, hepatitis B surface antigen, hepatitis C antibodies, syphilis antibodies ECG QTc > 450 ms, QRS > 110 ms, intermittent bundle branch block, frequent premature atrial or ventricular contractions at the time of screening, or any person who is considered clinically significant by the investigator; 4) A routine blood test with a white blood cell count, neutrophil count and lymphocyte count outside the normal reference range at screening and judged clinically significant by the investigator; 5) A kidney disease diet adjustment ( MDRD) formula calculated with an estimated glomerular filtration rate (eGFR) < 90 mL Sensitivity to thyroid medication or history of sensitivity to a similar study drug(eg.MGL-3196) History of sensitivity to a similar study drug Major surgical procedure, previous gastrointestinal surgery, vagotomy, bowel resection or any surgical procedure that may interfere with peristalsis, pH or absorption in the gastrointestinal tract within 6 months prior to screening Subjects who, in the judgement of the investigator, have a condition that affects the absorption, distribution, metabolism and excretion of the drug (e.g. gastrointestinal dysfunction, peptic ulcer, gastrointestinal surgery, etc.) or who are unable to comply with a uniform diet during the trial Taken any prescription medication, over-the-counter medication, any vitamin product or herbal remedy within 1 month prior to screening Subjects with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results interpretation History of regular use nicotine or alcohol，unable to abstain from smoking and alcohol during the trial Previous blood donation or blood loss of more than 400 mL within 3 months prior to taking the study drug Had consumed a special diet (including popcorn, dragon fruit, mango, grapefruit, orange, etc.) or alcohol within 2 weeks before taking the study drug, or had strenuous exercise Taken an experimental drug or other experimental treatment within 3 months prior to screening, or being involved in any other interventional clinical trial Nursing female subjects Any other condition that, in the opinion of the investigator or sponsor, makes the subject unsuitable for inclusion in the study

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RJ4287 Tablets<br>single-dose or Multiple-doses, ascending dosing groups (cohorts) will be evaluated | Drug: RJ4287<br>* Oral，tablets，Once daily for 14 days<br>|
| Placebo Comparator: Placebo<br>Single or multiple doses of Placebo | Drug: Placebo<br>* Oral，tablets，Once daily daily for 14 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Safety measurements will include vital signs, hematology, blood chemistry, blood pressure and other readouts. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameters of blood | To measure the plasma concentration of RJ4287 in single and multiple doses | 2 weeks | 
| Pharmacokinetics parameters of urine | Accumulated excretion | 2 weeks | 
| Pharmacokinetics parameters of faeces | Accumulated excretion | 2 weeks | 
| Change in lipid / lipoprotein levels from baseline through Day 14 in Multiple Dose | compare with placebo | 2 weeks |