Clinical trial NCT04293965: Single-dose and Multiple-dose X842 Phase 1 Study
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single-dose and Multiple-dose X842 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Potassium competitive acid blocker
Esophagitis
X842
Intragastric pH
Gastroesophageal reflux disease
GERD
Acid inhibition
Lead sponsor: Jiangsu Sinorda Biomedicine Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-03-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: SAD, MAD and FE study
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence and frequency of AEs after single and multiple doses of X842.
timeFrame: Five Weeks
measure: Vital signs of body temperature
timeFrame: Five Weeks
measure: Vital signs of blood pressure
timeFrame: Five Weeks
measure: Vital signs of respiratory rate
timeFrame: Five Weeks
measure: Physical Examination of height
timeFrame: Five Weeks
measure: Physical Examination of weight
timeFrame: Five Weeks
measure: Number of clinically significant changes in Electrocardiograms (ECGs)
timeFrame: Five Weeks
measure: Number of Clinically significant changes in lab assessment of blood serum
timeFrame: Five Weeks
measure: Number of Clinically significant changes in the lab assessment of blood
timeFrame: Five Weeks
measure: Number of Clinically significant changes in the lab assessment of urine
timeFrame: Five Weeks
Secondary outcomes:
measure: Measurement of the PK profile (Cmax)
timeFrame: Up to 48 hours after dosing
measure: Measurement of the PK profile (t1/2)
timeFrame: Up to 48 hours after dosing
measure: Measurement of the PD profile (intragastric pH)
timeFrame: Up to 24 hours after dosing
Other outcomes:
Locations:
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
Study officials:
affiliation: Jiangsu Sinorda Biomedicine Co., Ltd
name: Pingsheng Hu, Ph.D
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.