Erosive EsophagitisPhase 1NCT05050188

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of Oral Doses of H008

A Phase 1 study testing H008 and Lansoprazole in people with Erosive Esophagitis, run by Jiangsu Carephar Pharmaceutical Co., Ltd. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Erosive Esophagitis
What is being tested?: H008 and Lansoprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 24 participants
Where: 1 siteUnited States
Study dates: 24 Jun 2021to 25 Sep 2021
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Adult, male and female volunteers, 18 to 55 years of age, inclusive, at the time of dosing.
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).
Willingness and ability to comply with study procedures and follow-up examination.
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.

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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.
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.
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.
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.
Non-smokers (including nicotine-containing products) for at least 3 continuous months prior to the first dose.

Who cannot join

A subject is not eligible for the study if any of the following criteria is met:
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.).
History of alcohol or drug/substance abuse (within 2 years).
Positive urine drug screen or alcohol breath test at screening or baseline (Day -2).
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.
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).

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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.
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.
History or clinical evidence of achlorhydria, severe gastrointestinal disease, particularly diarrhea or other conditions affecting gastrointestinal mobility or absorption.
Subjects who have difficulty in swallowing oral tablets or capsules.
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.
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;
Subjects who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody.
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.
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.
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.
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.
Females who are pregnant, lactating, or likely to become pregnant during the study.
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.
Other conditions that an Investigator believes are not suitable for participation in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Syneos Health
Miami, Florida, 33136

Other trials in United States

About this study

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

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.

Read the detailed description

Screening Period

After signing the informed consent, all subjects will undergo a screening assessment within 4 weeks prior to the start of study treatment (Days -28 to -3).

Baseline Period

Eligible subjects at screening will come to the clinic 2 days prior to the first dosing and begin their 11-day confinement period (Day -2 to Day 9). On Day -2, subjects will undergo baseline examinations. On Day -1, subjects will be monitored for their intragastric pH using a pH probe inserted into the stomach. The intragastric pH will be measured continuously for 48 h (Day -1 to Day 2), and data within the first 24 h will be used as baseline for PD evaluation. Subject's eligibility will be confirmed prior to first dosing (morning of Day 1).

Repeated-dose Period On each day during the treatment period, subjects will receive the investigational product (H008, 20 mg or 40 mg), matching placebos or positive control drug (Lansoprazole, 30 mg) according to the randomization schedule after a minimum 10-hour overnight fasting. No water is allowed within 1 hour before the drug administration. Subjects will be instructed to take the drugs with approximately 240 mL (8 oz) room temperature water, and swallow the tablets or capsules whole without chewing. On Days 1 to 7, no food or water is allowed within at least 2 hours post-dose, except the water ingested during dosing. Subjects should avoid lying down for 2 hours post-dose, except when ECG or vital sign measurements are performed. Standard lunch and dinner will be provided at approximately 4 and 10 hours post-dose on Days 1 and 7. On Days 2 to 6, standard breakfast, lunch and dinner will be provided at approximately 2, 5 and, 10 hours post-dose.

Serial PK blood samples will be collected for all subjects from pre-dose (Day 1) to 48 h after the last dose (Day 9). Detailed PK sampling plan is presented in Table 1.3-1. Another 24-h intragastric pH measurement will be performed from pre-dose on Day 7 until 24 h after the Day 7 dosing. All subjects will be closely monitored for safety during their stay in the clinic. Subjects will be discharged 48 hours after their last dosing (Day 9) if no clinically significant adverse events occur.

Follow-up Period

A follow-up safety assessment will be performed on Day 16 ± 1 at clinic. Unscheduled follow-ups should be performed for any clinically significant AE until it returns to normal or baseline or steady state.

Conditions: Erosive Esophagitis
Being tested: H008, H008 placebo, Lansoprazole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

H008Drug
Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water.
H008 placeboDrug
Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water
LansoprazoleDrug
Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water

Study groups in NCT05050188
Study group	Role	What they receive
cohort 1: H008 20mg	Experimental	H008 20mg tablets, orally, once, daily, for 7 days Receives: Drug: H008
cohort 1: H008 placebo 20mg	Experimental	H008 placebo 20mg tablets, orally, once, daily, for 7 days Receives: Drug: H008 placebo
cohort 1: Lansoprazole 30mg	Experimental	Lansoprazole 30mg capsule, orally, once, daily, for 7 days Receives: Drug: Lansoprazole
cohort 2: H008 40mg	Experimental	H008 40mg tablets, orally, once, daily, for 7 days Receives: Drug: H008
cohort 2: H008 placebo 40mg	Experimental	H008 placebo 40mg tablets, orally, once, daily, for 7 days Receives: Drug: H008 placebo
cohort 2: Lansoprazole 30mg	Experimental	Lansoprazole 30mg capsule, orally, once, daily, for 7 days Receives: Drug: Lansoprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

The number and incidence of AEs in HVs of multiple oral dose of H008 (Safety and Tolerability)
AEs
Measured: Up to final follow-up (Day16) or early termination.
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.
Measured: Baseline up to Day 16
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）.
Measured: Baseline up to Day 16
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
Measured: Baseline up to Day 16
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.
Measured: Baseline up to Day 16

Secondary outcomes (14)

To characterize the PK profiles of multiple oral doses of H008 in HVs.
AUC0-t.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
AUC0-tau.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
AUC0-inf (if feasible).
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Cmax.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Ctroughs.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Tmax.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Kel.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
T1/2.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
CL/F.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Vd/F.
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Accumulation index (with steady state dosing).
Measured: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Peak/trough fluctuation after single and multiple oral doses of H008.
Measured: through study completion,an average of 1 year
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
Measured: 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.
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
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jun 202125 Sep 2021

First posted20 Sep 2021
Study start24 Jun 2021
Primary completion18 Sep 2021
Study completion25 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (17)Papers the sponsor has linked to this study.
Other trials for Erosive EsophagitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: 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. 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.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05050188
Sponsor's protocol ID: KFP-2020-H008-HW-101
Status last verified: Dec 2023
First submitted: 9 Jun 2021
Last updated: 15 Dec 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 7605854
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.
PubMed 32095968
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.
PubMed 9178669
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.
PubMed 15831922
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.
PubMed 26369775
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.
PubMed 23853213
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.
PubMed 17245209
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.
PubMed 19365600
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.
PubMed 10452674
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.
PubMed 9794192
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.
PubMed 15882117
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.
PubMed 11095320
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.
PubMed 24466441
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.
PubMed 11148442

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Erosive Esophagitis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05050188
Acronym / sponsor ID: KFP-2020-H008-HW-101
Conditions: Erosive Esophagitis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Jiangsu Carephar Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 24 Jun 2021 (actual)
Primary completion: 18 Sep 2021 (actual)
Study completion: 25 Sep 2021 (actual)
First posted: 20 Sep 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

The study will consist of a screening period, a baseline period, a 7-day repeated-dose period and a safety follow-up period.

Detailed description

Screening Period

After signing the informed consent, all subjects will undergo a screening assessment within 4 weeks prior to the start of study treatment (Days -28 to -3).

Baseline Period

Follow-up Period

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 6
Model description: 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. 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.

Arm	Type	Receives
cohort 1: H008 20mg	Experimental	Drug: H008H008 20mg tablets, orally, once, daily, for 7 days
cohort 1: H008 placebo 20mg	Experimental	Drug: H008 placeboH008 placebo 20mg tablets, orally, once, daily, for 7 days
cohort 1: Lansoprazole 30mg	Experimental	Drug: LansoprazoleLansoprazole 30mg capsule, orally, once, daily, for 7 days
cohort 2: H008 40mg	Experimental	Drug: H008H008 40mg tablets, orally, once, daily, for 7 days
cohort 2: H008 placebo 40mg	Experimental	Drug: H008 placeboH008 placebo 40mg tablets, orally, once, daily, for 7 days
cohort 2: Lansoprazole 30mg	Experimental	Drug: LansoprazoleLansoprazole 30mg capsule, orally, once, daily, for 7 days

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (17 listed)

Adult, male and female volunteers, 18 to 55 years of age, inclusive, at the time of dosing.
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).
Willingness and ability to comply with study procedures and follow-up examination.
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.
Use of hormonal contraceptive methods will not be allowed.

Key exclusion criteria (20 listed)

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.).
History of alcohol or drug/substance abuse (within 2 years).
Positive urine drug screen or alcohol breath test at screening or baseline (Day -2).
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.
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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
H008Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water.	Drug	cohort 1: H008 20mg, cohort 2: H008 40mg
H008 placeboDrug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water	Drug	cohort 1: H008 placebo 20mg, cohort 2: H008 placebo 40mg
LansoprazoleDrug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water	Drug	cohort 1: Lansoprazole 30mg, cohort 2: Lansoprazole 30mg

Primary outcome

The number and incidence of AEs in HVs of multiple oral dose of H008 (Safety and Tolerability)
Time frame: Up to final follow-up (Day16) or early termination.
AEs
The number and incidence of subjects with clinically significant changes of physical examinations (Safety and Tolerability)
Time frame: Baseline up to Day 16
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.
The number and incidence of subjects with abnormal vital signs of multiple oral dose of H008 (Safety and Tolerability)
Time frame: Baseline up to Day 16
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）.
The number and incidence of subjects with clinical defined abnormal laboratory tests of multiple oral dose of H008 (Safety and Tolerability)
Time frame: Baseline up to Day 16
hematology，blood chemistry,urinalysis
The number and incidence of subjects with clinical defined abnormal of 12-lead ECG multiple oral dose of H008 (Safety and Tolerability)
Time frame: Baseline up to Day 16
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.

14 secondary outcomes

To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
To characterize the PK profiles of multiple oral doses of H008 in HVs.
Time frame: through study completion,an average of 1 year
Percentage of Time the pH is Greater than pH 3, pH 4 and pH 5 over a 24 Hour Period
Time frame: 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.
Percentage of Time the PH is Greater than pH 3, pH 4 and pH 5 from 8 PM to 8 AM
Time frame: 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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
Background: PubMed 7605854Bardhan 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.
Background: PubMed 32095968Cheng 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.
Background: PubMed 9178669Chiba 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.
Background: PubMed 15831922Dent 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.
Background: PubMed 26369775Echizen 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.
Background: PubMed 23853213El-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.
Background: PubMed 17245209Fass 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.
Background: PubMed 19365600Fujiwara 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.
Background: PubMed 10452674Furukawa 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.
BackgroundKusano. 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
Background: PubMed 9794192Maekawa 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.
Background: PubMed 15882117Parsons 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing H008 and Lansoprazole in people with Erosive Esophagitis, run by Jiangsu Carephar Pharmaceutical Co., Ltd. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number and incidence of AEs in HVs of multiple oral dose of H008 (Safety and Tolerability) (time frame: Up to final follow-up (Day16) or early termination.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05050188, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.