Single-dose and Multiple-dose X842 Phase 1 Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of X842 after administration of single and multiple doses in healthy subjects

Detailed Description
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This is a single-center, open label, First-In-human (FIH), Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of single dose and multiple doses of X842 capsules in healthy subjects. The study comprises a Single Ascending Dose (SAD) part, a Multiple Ascending Dose (MAD) part, and a Food Effect (FE) study.

Official Title
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A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single-dose and Multiple-dose X842 in Healthy Subjects.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Single ascending dose of X842
* Drug: Multiple ascending dose of X842
* Other: Food Effect


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those aged 18-45 years old (inclusive the upper and lower limits). Body weight of ≥ 50kg for male and ≥ 45kg for female , with a body mass index (BMI) of 19.0-26.0 kg/m2 (inclusive the upper and lower limits, BMI = weight (kg) / height (m) 2). Understand and able to give written informed consent form for participation in this study voluntarily. Those who fail to meet any of the above conditions shall not be enrolled. Exclusion Criteria: Those who meet any of the following conditions shall not be enrolled: History of any clinically significant disease or disorder in cardiovascular system, respiratory system, digestive system, endocrine system, nervous/mental system, blood and lymphatic system, and musculoskeletal system according to the investigator. Comprehensive physical examination, vital signs, laboratory test, 12-lead ECG, or chest X-ray examination (anteroposterior and lateral view) suggests that there are abnormalities that are determined by the investigator to be clinically significant. Those who received helicobacter pylori eradication therapy within 6 months prior to the study drug administration; The results of helicobacter pylori screening (C-14 urea breath test) is positive; Any positive result for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV), or Treponema pallidum antibody (TP-Ab). History of any food or drug allergy, or any other history of allergic disease (such as asthma, urticaria, and eczematous dermatitis, etc.) considered as clinical significant by the investigator. Subjects who had taken any drug within 2 weeks prior to screening, which may affect the results of the study according to the investigator. History of drug abuse within 12 months prior to screening or positive urine drug result at screening. Those who regularly drink alcohol within 6 months prior to screening, that is, more than 14 units of alcohol weekly (1 unit = 360 mL of beer or 45 mL of spirit with 40% alcohol or 150 mL of wine), or those who could not guarantee the abandonment of drinking during the study, or subjects with positive result of alcohol breath test. Subjects who smoke more than 5 cigarettes daily within 3 months prior to screening or those could not guarantee the abandonment of smoking during the study. Those who have participated in any other drug clinical trial within 3 months prior to screening (with the last visit date of the trial considered as the starting time for time counting). Those who donated blood or blood products of ≥400ml or 2 units within 3 months or had lost of ≥400 mL blood within 6 months prior to screening. Those who do not agree to stop alcohol drinking or caffeinated beverages within 48 hours before the study drug administration and throughout the whole trial, or do not agree to stop strenuous exercise or to avoid other factors that may affect the drug absorption, distribution, metabolism, or excretion. Women who are pregnant or lactating, or who have a positive pregnancy test before the study drug administration; or those who could not or do not take the requested effective contraceptive measures accepted by the investigator during the trial. Subjects with difficulties in venous blood collection, fear of needles or hemophobia. Other conditions that may not be suitable for participating in the study judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: SAD, MAD and FE study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose Study<br>Healthy subjects will be screened and different doses of X842 will be administered in a single dose to assess the safety, tolerability, PK and PD profile of X842. | Drug: Single ascending dose of X842<br>* A total of 7 dose groups will be set for the ascending dose: 5.6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 225 mg. In the 5.6 mg dose group, 4 subjects will receive X842; in the 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 225 mg dose groups, 8 subjects in each group will receive X842. Each subject can only receive a certain dose level and cannot enter in multiple dose groups repeatedly.<br>* Other names: X842;|
| Experimental: Multiple Ascending Dose Study<br>Healthy subjects will be screened and different doses of X842 will be administered in multiple doses to assess the safety, tolerability, PK and PD profile of X842. The dose ascending at this stage will be based on the results of the single dose tolerability study. | Drug: Multiple ascending dose of X842<br>* Two dose groups will be set, including the groups receiving the recommended phase II dose and a higher dose; Eight subjects will be enrolled in each group, with half male and half female, who will receive X842 once daily for 5 consecutive days. Each subject can only receive a certain dose level and cannot enter in multiple dose groups repeatedly.<br>* Other names: X842;|
| Experimental: Food Effect Study<br>A randomized, open label, single-dose, self-controlled, double-cycle, two-way crossover clinical trial. | Other: Food Effect<br>* Twelve subjects (appropriate ratio of male to female) screened for eligibility will be randomized into Group A and B. The 6 subjects in Group A will take the study drug (X842) in fasted condition and subject in Group B will take the study drug in fed condition in the 1st cycle. In the 2nd Cycle, subjects in Group A will take the study drug in fed condition, and subjects in Group B will take the study drug in fasted condition. The interval between the two cycles is at least 7 days.<br>* Other names: X842;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and frequency of AEs after single and multiple doses of X842. | Safety and tolerability will be assessed by occurrence and frequency of AEs. The adverse event assessment will follow the recommendations and grading system of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Summary statistics will be applied. | Five Weeks | 
| Vital signs of body temperature |  | Five Weeks | 
| Vital signs of blood pressure | Blood pressure measurements included systolic (mmHg) and diastolic (mmHg). | Five Weeks | 
| Vital signs of respiratory rate |  | Five Weeks | 
| Physical Examination of height |  | Five Weeks | 
| Physical Examination of weight |  | Five Weeks | 
| Number of clinically significant changes in Electrocardiograms (ECGs) | The investigator or the sub-investigator interpreted the ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant. | Five Weeks | 
| Number of Clinically significant changes in lab assessment of blood serum |  | Five Weeks | 
| Number of Clinically significant changes in the lab assessment of blood |  | Five Weeks | 
| Number of Clinically significant changes in the lab assessment of urine |  | Five Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the PK profile (Cmax) | To assess the Maximum Plasma Concentration (Cmax) | Up to 48 hours after dosing | 
| Measurement of the PK profile (t1/2) | To assess the plasma half life (t1/2) of drug | Up to 48 hours after dosing | 
| Measurement of the PD profile (intragastric pH) | To assess and characterize the PD profile with measurements of intragastric pH | Up to 24 hours after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagitis, Potassium competitive acid blocker, X842, Intragastric pH, Gastroesophageal reflux disease, GERD, Acid inhibition