Single-dose and Multiple-dose X842 Phase 1 Study

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Single ascending dose of X842; Drug: Multiple ascending dose of X842; Other: Food Effect

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • The Affiliated Hospital of Guizhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Those aged 18-45 years old (inclusive the upper and lower limits).
2. 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).
3. 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:

1. 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.
2. 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.
3. Those who received helicobacter pylori eradication therapy within 6 months prior to the study drug administration;
4. The results of helicobacter pylori screening (C-14 urea breath test) is positive;
5. 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).
6. 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.
7. Subjects who had taken any drug within 2 weeks prior to screening, which may affect the results of the study according to the investigator.
8. History of drug abuse within 12 months prior to screening or positive urine drug result at screening.
9. 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.
10. 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.
11. 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).
12. 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.
13. 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.
14. 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.
15. Subjects with difficulties in venous blood collection, fear of needles or hemophobia.
16. Other conditions that may not be suitable for participating in the study judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose Study; 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; 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.; Other Names: X842
Experimental: Multiple Ascending Dose Study; 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; 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.; Other Names: X842
Experimental: Food Effect Study; A randomized, open label, single-dose, self-controlled, double-cycle, two-way crossover clinical trial.	Other: Food Effect; 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.; Other Names: X842

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu Sinorda Biomedicine Co., Ltd
• Investigators: Study Chair: Pingsheng Hu, Ph.D, Jiangsu Sinorda Biomedicine Co., Ltd

Publications and helpful links

General Publications

• El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80. doi: 10.1136/gutjnl-2012-304269. Epub 2013 Jul 13.
• Yuan Y, Hunt RH. Evolving issues in the management of reflux disease? Curr Opin Gastroenterol. 2009 Jul;25(4):342-51. doi: 10.1097/MOG.0b013e32832c1504.
• Dent J, Kahrilas PJ, Hatlebakk J, Vakil N, Denison H, Franzen S, Lundborg P. A randomized, comparative trial of a potassium-competitive acid blocker (AZD0865) and esomeprazole for the treatment of patients with nonerosive reflux disease. Am J Gastroenterol. 2008 Jan;103(1):20-6. doi: 10.1111/j.1572-0241.2007.01544.x.
• Kahrilas PJ, Dent J, Lauritsen K, Malfertheiner P, Denison H, Franzen S, Hasselgren G. A randomized, comparative study of three doses of AZD0865 and esomeprazole for healing of reflux esophagitis. Clin Gastroenterol Hepatol. 2007 Dec;5(12):1385-91. doi: 10.1016/j.cgh.2007.08.014. Epub 2007 Oct 22.
• Nilsson, Albrektson E, Rydholm H, Rohss K, Alin MH, Hasselgren G. Tolerability, Pharmacokinetics and Effects on Gastric Acid Secretion After Single Oral Doses of the Potassium-Competitive Acid Blocker (P-CAB) AZD0865 in Healthy Male Subjects. Gastroenterology 2005 Volume 128, Issue 4, Supplement 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2018
• Primary Completion (Actual): September 4, 2019
• Study Completion (Actual): September 4, 2019

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: GERD; Esophagitis; Gastroesophageal reflux disease; Potassium competitive acid blocker; X842; Intragastric pH; Acid inhibition
• Other Study ID Numbers: SND-X842-101; CTR20181666 (Other Identifier: Center for drug evaluation, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No