A Multiple Ascending Dose Pharmacology Study of Anaprazole in Healthy Chinese Subjects

Study Overview
=================
Brief Summary
-----------------
A single-center, randomized, double-blinded, placebo parallel controlled phase 1 study to evaluate the safety and pharmacokinetics/pharmacodynamics of multiple (6 days) ascending dose (20mg QD, 40mg QD, 20mg Bid) administrationof Anaprazole in healthy Chinese subjects. 36 subjects, 12 subjects for each dose group. In each dose group, 10 subjects take anaprazole, 2 subjects take placebo.

Official Title
-----------------
A Single-center, Randomized, Double-blinded, Placebo Parallel Controlled Phase 1 Study to Evaluate the Safety and Pharmacokinetics/Pharmacodynamics of Multiple Ascending Dose Administration of Anaprazole in Healthy Chinese Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Anaprazole Sodium enteric-coated tablet
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is capable of understanding and complying with protocol requirements, and signed and dated a written informed consent form voluntarily; The subject is a Chinese health adult, aged 18 to 45 years, inclusive; The subject weighed at least 50.0 kg and had a body mass index (BMI) between 19.0 kg/m^2 and 24.0 kg/m^2, inclusive; Has clinical laboratory evaluations, vital signs and ECG testing within the reference range, and medical history and physicial examination results are normal. Participants with evaluations outside the reference range that are deemed not clinically significant by the investigator may be included at investigator discretion; No medical history of allergy to proton pump inhibitors and no any other drug allergy history; The subjects have a good lifestyle and can keep good communication with the investigators and comply with the requirements of clinical trial. Exclusion Criteria: Has postural hypotension, gastrointestinal disease (gastric ulcer, gastritis and etc), liver disease, renal disease (nephritis, pyelonephritis and etc), and other disease or medical history of any other system (cardiovascular, respiratory, psychoneural, hematology, endocrinology and etc) ; Has clinical significant abnormal electrolytes (especially hypopotassemia) in screening examination; Has clinical significant ECG abnormal history or family history of long QT syndrome(Grandparents, parents and siblings); Has rhinitis, allergic rhinitis, recurrent hemorrhinia, nasal deformity and abnormal nasal septum； With positive result of drug screening test; With positive result of nicotine test; Female participants who are pregnant, breast-feeding or menstral period, or participants has no effective contraception method, or has pregnancy plan in 6 months; Has received any drugs: acid-inhibitors, any priscription drug, herb medicine, non-prescription drugs and/or food suppliments (including vitamine) within 2 weeks before randomization; Blood donation / blood loss ≥400 mL within 3 months, or participated any other clinical trials within 3 months; Known Human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, and Treponema pallidum specific antibody test results were positive at screening; Frequent alcoholics (drink more than 2 units of alcohol per day, 1 unit = 330 mL beer or 25 mL liquor or 125 mL wine), or took food or drinks with alcoholics 72 hours before randomization; Has taken foods or drinks with xanthine(cafeine) or intensive excercise. Has taken foods or drinks that affect CYP3A4 (such as grapefruit or beverages containing grapefruit) within 14 days before administration of investigational drugs; Smoke more than 5 pieces per week; Any conditions in which considered by investigator not be appropriate to participate in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 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: Anaprazole Sodium enteric-coated tablet<br>Multiple ascendinng dose, anaprazole 20mg QD(20mg QD group), 40mg QD(40mg QD group), 20mg Bid(20mg Bid group) , 6 days, fasting oral administration. | Drug: Anaprazole Sodium enteric-coated tablet<br>* Multiple ascendinng dose, anaprazole 20mg QD(20mg QD group), 40mg QD(40mg QD group), 20mg Bid(20mg Bid group) , 6 days, fasting oral administration.<br>|
| Placebo Comparator: Placebo<br>Multiple dose, 1 tablet QD (20mg QD and 40mg QD group), 1 tablet Bid (20mg Bid group), 6 days, fasting oral administration. | Drug: Placebo<br>* Multiple dose, 1 tablet QD (20mg QD and 40mg QD group), 1 tablet Bid (20mg Bid group), 6 days, fasting oral administration.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events and serious adverse events as assessed by CTCAE v5.0 | All adverse events will be monitored in each subject | From signing informed consent to study completion, 15 days after fist dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites | AUC is area under the plasma concentration-time curve | 10 minutes pre-dose and 1.5、2、2.5、3、3.5、4、4.5、5、6、7、8、10、12、15、24 hours post-dose of Day 0 and Day 6 | 
| Cmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites | Cmax is the peak plasma concentration | 10 minutes pre-dose and 1.5、2、2.5、3、3.5、4、4.5、5、6、7、8、10、12、15、24 hours post-dose of Day 0 and Day 6 | 
| Tmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites | Tmax is the time to peak plasma concentration | 10 minutes pre-dose and 1.5、2、2.5、3、3.5、4、4.5、5、6、7、8、10、12、15、24 hours post-dose of Day 0 and Day 6 | 
| Time percentage of gastric pH value>3 in 24 hours gastric pH monitoring post dose at day 6 | Time percentage gastric pH value>3 is duration (hours) of gastric pH value>3 divided to 24 hours | 24 hours post-dose at day 6 | 
| Time percentage of gastric pH value>4 in 24 hours gastric pH monitoring post dose at day 6 | Time percentage gastric pH value>4 is duration (hours) of gastric pH value>3 divided to 24 hours | 24 hours post-dose at day 6 |