Erosive Esophagitis Clinical Trial
Official title:
A Phase I, Randomized, Double-blind, Placebo- and Positive-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics (PK/PD) of Multiple Oral Doses of H008 (Carenoprazan Hydrochloride Tablets) in Healthy Volunteers
Verified date | December 2023 |
Source | Jiangsu Carephar Pharmaceutical Co., Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This will be a Phase I, randomized, double-blind, positive- and placebo-controlled study to evaluate the safety, tolerability, and PK/PD of multiple oral doses of H008 in healthy adult subjects. Two dose levels of H008 at 20 mg and 40 mg will be studied in two sequential cohorts. Each cohort will be enrolled with 12 subjects (8 on H008, 2 on placebo and 2 on positive control drug). Subjects are only allowed to participate in one of the two cohorts. Both the investigational product and placebo will be given in a double blinded manner, while the positive control drug will be given in an open-label manner.Dose escalation to the next cohort will be permitted only when safety data until follow-up and PK data until 48 hours post-last dose, from all subjects in previous cohorts are reviewed, and the investigational product is deemed well tolerated. The study will consist of a screening period, a baseline period, a 7-day repeated-dose period and a safety follow-up period.
Status | Completed |
Enrollment | 24 |
Est. completion date | September 25, 2021 |
Est. primary completion date | September 18, 2021 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility | Inclusion Criteria: 1. Adult, male and female volunteers, 18 to 55 years of age, inclusive, at the time of dosing. 2. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures). 3. Willingness and ability to comply with study procedures and follow-up examination. 4. Body mass index (BMI) =18 to =30 kg/m2 and total body weight =50.0 kg for males and =45.0 kg for females at screening. - If female and of childbearing potential (premenopausal and not surgically sterile), the subject:Must have a negative serum pregnancy test at screening. The serum pregnancy test must be obtained prior to the first administration of H-008 (=72 hours prior to dosing) in all women. - Must agree to use an acceptable method of effective contraception for the duration of the study and for 3 months after receiving the last dose of study treatment. If male, the subject agrees to: - Use an acceptable method of effective contraception (a dual method of contraception: condom with spermicide in conjunction with use of an intrauterine device (IUD), condom with spermicide in conjunction with use of a diaphragm, condom with birth control patch or vaginal ring, or condom with oral, injectable, or implanted contraceptive) for the duration of the study and for 3 months after receiving study treatment. - Abstain from sperm donation for the duration of the study and for 90 days after receiving the last dose of study treatment. - Ensure their partner not get pregnant until 3 months following administration of the last dose of study treatment. - Be vasectomized for at least 6 months or take appropriate precautions to avoid fathering a child. - Male subjects who do not have sexual partners, they need to agree to remain abstinent at the time of screening, or agree to use a double barrier if they become sexually active. Use of hormonal contraceptive methods will not be allowed. 5. Medically healthy on the basis of medical history, and physical examination (including but not limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), as determined by the Investigator at Screening and each Check-In visit. 6. Medically healthy based on the absence of clinically significant abnormal vital sign measurements, clinical laboratory test results (especially tests for renal and hepatic function) as determined by the Investigator at Screening and Check-In visit. 7. Medically healthy based on the absence of clinically significant abnormal vital sign measurements, clinical laboratory test results (especially tests for renal and hepatic function) as determined by the Investigator at Screening and each Check-In visit. 8. Non-smokers (including nicotine-containing products) for at least 3 continuous months prior to the first dose. Exclusion Criteria: A subject is not eligible for the study if any of the following criteria is met: 1. Subjects who have a history of drug allergy or atopic allergic disease (e.g. asthma, urticaria, eczema, dermatitis, etc.) that were clinically significant, or allergic to any known ingredients and excipients of H008 and other PPIs drugs (e.g., Omeprazole, Lansoprazole, Ilaprazole, Esomeprazole, Rabeprazole, etc.). 2. History of alcohol or drug/substance abuse (within 2 years). 3. Positive urine drug screen or alcohol breath test at screening or baseline (Day -2). 4. Subjects who have history of unexplained syncope or fainting or a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia or dehydration. 5. Subjects determined by the Investigator to have any medical condition that could jeopardize their health or prejudice study results (e.g., history of surgery of the gastrointestinal tract, which may interfere with absorption, except for appendectomy and cholecystectomy). 6. Subjects who have used P-gp and/or CYP 450 hepatic microsomal enzyme-inducing or inhibiting drugs (e.g., propafenone, voriconazole, fluconazole, cimetidine) within 30 days of first dosing. 7. Subjects with history or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease, or active sexually transmitted disease. 8. History or clinical evidence of achlorhydria, severe gastrointestinal disease, particularly diarrhea or other conditions affecting gastrointestinal mobility or absorption. 9. Subjects who have difficulty in swallowing oral tablets or capsules. 10. History or presence of significant cardiovascular abnormalities, including without limitation, severe bradycardia, sick sinus syndrome, second- or third-degree atrial ventricular block, long QT syndrome, cardiogenic shock, and decompensated heart failure. 11. History or presence of pro-arrhythmic conditions, including a marked baseline prolongation of QTcF interval (i.e., repeated demonstration of a QTcF interval >450 milliseconds for males and >470 milliseconds for females) or a history of additional significant risk factors for torsade de pointes (e.g., family history of long QT syndrome), including any evidence of QTcF prolongation at screening; 12. Subjects who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody. 13. Subject is unable to refrain from or anticipated the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [hypericum perforatum]), or grapefruits, grapefruit juice, blood oranges, apples and mulberry juice as well as vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard greens) beginning approximately 2 weeks prior to administration of the initial dose of investigational product, throughout the study, until the poststudy visit. Use of hormonal contraceptive methods will not be allowed. 14. Subjects donated blood (excluding plasma donation) of approximately 500 mL within 56 days prior to first dosing or donated plasma within 7 days prior to first dosing. Subjects will be advised not to donate plasma for 14 days after completing the study. 15. Subject consumes excessive amounts of caffeine for one month prior to investigational product administration, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day. 16. Subjects who have participated in any other clinical trial within 30 days prior to the screening or five half lives of the investigational product received in the other trial. 17. Females who are pregnant, lactating, or likely to become pregnant during the study. 18. Abnormal gastric pH rhythms over 12 hours on Day -1, including abnormal pH increase lasting for more than 1 hour during non-eating or supine period, as judged by the physician. 19. Other conditions that an Investigator believes are not suitable for participation in the study. |
Country | Name | City | State |
---|---|---|---|
United States | Syneos Health | Miami | Florida |
Lead Sponsor | Collaborator |
---|---|
Jiangsu Carephar Pharmaceutical Co., Ltd. |
United States,
Bardhan KD, Hawkey CJ, Long RG, Morgan AG, Wormsley KG, Moules IK, Brocklebank D. Lansoprazole versus ranitidine for the treatment of reflux oesophagitis. UK Lansoprazole Clinical Research Group. Aliment Pharmacol Ther. 1995 Apr;9(2):145-51. doi: 10.1111/j.1365-2036.1995.tb00363.x. — View Citation
Cheng Y, Liu J, Tan X, Dai Y, Xie C, Li X, Lu Q, Kou F, Jiang H, Li J. Direct Comparison of the Efficacy and Safety of Vonoprazan Versus Proton-Pump Inhibitors for Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2021 Jan;66(1):19-28. doi: 10.1007/s10620-020-06141-5. Epub 2020 Feb 24. — View Citation
Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997 Jun;112(6):1798-810. doi: 10.1053/gast.1997.v112.pm9178669. — View Citation
Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005 May;54(5):710-7. doi: 10.1136/gut.2004.051821. — View Citation
Echizen H. The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016 Apr;55(4):409-18. doi: 10.1007/s40262-015-0326-7. — View 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. — View Citation
Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol. 2007 Feb;41(2):131-7. doi: 10.1097/01.mcg.0000225631.07039.6d. — View Citation
Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44(6):518-34. doi: 10.1007/s00535-009-0047-5. Epub 2009 Apr 14. — View Citation
Furukawa N, Iwakiri R, Koyama T, Okamoto K, Yoshida T, Kashiwagi Y, Ohyama T, Noda T, Sakata H, Fujimoto K. Proportion of reflux esophagitis in 6010 Japanese adults: prospective evaluation by endoscopy. J Gastroenterol. 1999 Aug;34(4):441-4. doi: 10.1007/s005350050293. — View Citation
Kusano. M, Hashizume. K, Ehara. Y, Mori M. Size of Hiatus Hernia Is Correlated with Kyphosis, Not with Obesity, in Elderly Japanese Women. Gastrointest Endosc. 2006;63(5):AB121. doi:10.1016/j.gie.2006.03.176
Maekawa T, Kinoshita Y, Okada A, Fukui H, Waki S, Hassan S, Matsushima Y, Kawanami C, Kishi K, Chiba T. Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan. J Gastroenterol Hepatol. 1998 Sep;13(9):927-30. doi: 10.1111/j.1440-1746.1998.tb00763.x. — View Citation
Maradey-Romero C, Fass R. New and future drug development for gastroesophageal reflux disease. J Neurogastroenterol Motil. 2014 Jan;20(1):6-16. doi: 10.5056/jnm.2014.20.1.6. Epub 2013 Dec 30. — View Citation
Parsons ME, Keeling DJ. Novel approaches to the pharmacological blockade of gastric acid secretion. Expert Opin Investig Drugs. 2005 Apr;14(4):411-21. doi: 10.1517/13543784.14.4.411. — View Citation
Richter JE, Bochenek W. Oral pantoprazole for erosive esophagitis: a placebo-controlled, randomized clinical trial. Pantoprazole US GERD Study Group. Am J Gastroenterol. 2000 Nov;95(11):3071-80. doi: 10.1111/j.1572-0241.2000.03254.x. — View Citation
Sharma VK, Leontiadis GI, Howden CW. Meta-analysis of randomized controlled trials comparing standard clinical doses of omeprazole and lansoprazole in erosive oesophagitis. Aliment Pharmacol Ther. 2001 Feb;15(2):227-31. doi: 10.1046/j.1365-2036.2001.00904.x. — View Citation
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x. — View Citation
Yadlapati R, Dakhoul L, Pandolfino JE, Keswani RN. The Quality of Care for Gastroesophageal Reflux Disease. Dig Dis Sci. 2017 Mar;62(3):569-576. doi: 10.1007/s10620-016-4409-6. Epub 2016 Dec 27. — View Citation
* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The number and incidence of AEs in HVs of multiple oral dose of H008 (Safety and Tolerability) | AEs | Up to final follow-up (Day16) or early termination. | |
Primary | The number and incidence of subjects with clinically significant changes of physical examinations (Safety and Tolerability) | A baseline physical examination (defined as the pretreatment assessment immediately prior to the start of study drug) will consist of the following body systems: eyes?ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. All subsequent physical examinations should assess clinically significant changes from the baseline examination. | Baseline up to Day 16 | |
Primary | The number and incidence of subjects with abnormal vital signs of multiple oral dose of H008 (Safety and Tolerability) | Subjects with vital signs included body temperature(?), blood pressure (both systolic and diastolic blood pressure ,mmHg), heart rate(beat per minute,BMP), and respiratory rate (beat per minute,BMP). | Baseline up to Day 16 | |
Primary | The number and incidence of subjects with clinical defined abnormal laboratory tests of multiple oral dose of H008 (Safety and Tolerability) | hematology,blood chemistry,urinalysis | Baseline up to Day 16 | |
Primary | The number and incidence of subjects with clinical defined abnormal of 12-lead ECG multiple oral dose of H008 (Safety and Tolerability) | Full 12-lead ECGs will be recorded using an ECG machine that automatically calculates the heart rate and measures HR?RR?PR, QRS, QT, QTc intervals. The investigator or other qualified physician will interpret each ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant. | Baseline up to Day 16 | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | AUC0-t. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | AUC0-tau. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | AUC0-inf (if feasible). | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Cmax. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Ctroughs. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Tmax. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Kel. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | T1/2. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | CL/F. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Vd/F. | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Accumulation index (with steady state dosing). | through study completion,an average of 1 year | |
Secondary | To characterize the PK profiles of multiple oral doses of H008 in HVs. | Peak/trough fluctuation after single and multiple oral doses of H008. | through study completion,an average of 1 year | |
Secondary | Percentage of Time the pH is Greater than pH 3, pH 4 and pH 5 over a 24 Hour Period | Over a 24-hour period at Baseline and over a 24-hour period following the administration of study on Days 1 and 7 | Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 24-hour period following the administration of study on Days 1 and 7. | |
Secondary | Percentage of Time the PH is Greater than pH 3, pH 4 and pH 5 from 8 PM to 8 AM | Over a 12-hour period from 8 PM to 8 AM on Days 1 and 7 | Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period from 8 PM to 8 AM to assess nocturnal pH |
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