Clinical trial NCT04466748: A Multiple Ascending Dose Pharmacology Study of Anaprazole in Healthy Chinese Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Sihuan Pharmaceutical Holdings Group Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. The subject is capable of understanding and complying with protocol requirements, and signed and dated a written informed consent form voluntarily;
2. The subject is a Chinese health adult, aged 18 to 45 years, inclusive;
3. 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;
4. 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;
5. No medical history of allergy to proton pump inhibitors and no any other drug allergy history;
6. The subjects have a good lifestyle and can keep good communication with the investigators and comply with the requirements of clinical trial.

Exclusion Criteria:

1. 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) ;
2. Has clinical significant abnormal electrolytes (especially hypopotassemia) in screening examination;
3. Has clinical significant ECG abnormal history or family history of long QT syndrome(Grandparents, parents and siblings);
4. Has rhinitis, allergic rhinitis, recurrent hemorrhinia, nasal deformity and abnormal nasal septum；
5. With positive result of drug screening test;
6. With positive result of nicotine test;
7. Female participants who are pregnant, breast-feeding or menstral period, or participants has no effective contraception method, or has pregnancy plan in 6 months;
8. 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;
9. Blood donation / blood loss ≥400 mL within 3 months, or participated any other clinical trials within 3 months;
10. Known Human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, and Treponema pallidum specific antibody test results were positive at screening;
11. 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;
12. 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;
13. Smoke more than 5 pieces per week;
14. Any conditions in which considered by investigator not be appropriate to participate in this trial.

Primary outcomes:
measure: Number of subjects with adverse events and serious adverse events as assessed by CTCAE v5.0
timeFrame: From signing informed consent to study completion, 15 days after fist dose administration
Secondary outcomes:
measure: AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites
timeFrame: 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
measure: Cmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites
timeFrame: 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
measure: Tmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites
timeFrame: 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
measure: Time percentage of gastric pH value>3 in 24 hours gastric pH monitoring post dose at day 6
timeFrame: 24 hours post-dose at day 6
measure: Time percentage of gastric pH value>4 in 24 hours gastric pH monitoring post dose at day 6
timeFrame: 24 hours post-dose at day 6
Other outcomes:
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