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| ID | Type | Description | Link |
|---|---|---|---|
| CTR20181666 | Other Identifier | Center for drug evaluation, NMPA |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Ascending Dose Study | Experimental | 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. |
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| Multiple Ascending Dose Study | Experimental | 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. |
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| Food Effect Study | Experimental | A randomized, open label, single-dose, self-controlled, double-cycle, two-way crossover clinical trial. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single ascending dose of X842 | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Pingsheng Hu, Ph.D | Jiangsu Sinorda Biomedicine Co., Ltd | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Affiliated Hospital of Guizhou Medical University | Guiyang | Guizhou | 550004 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23853213 | Background | 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. | |
| 19417644 | Background | 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. |
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| ID | Term |
|---|---|
| D004941 | Esophagitis |
| D005764 | Gastroesophageal Reflux |
| ID | Term |
|---|---|
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D005759 | Gastroenteritis |
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SAD, MAD and FE study
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| Multiple ascending dose of X842 | Drug | 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. |
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| Food Effect | Other | 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. |
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| Five Weeks |
| Number of Clinically significant changes in the lab assessment of urine | Five Weeks |
| 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 |
| 18184117 | Background | 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. |
| 17950677 | Background | 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. |
| Background | 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. |
| D015154 | Esophageal Motility Disorders |
| D003680 | Deglutition Disorders |