Dose-Effect of S-Tenatoprazole-Na(STU-Na) 30 mg, 60 mg, 90 mg and 120 mg in Healthy Volunteers - Full Text View

Sponsors and Collaborators:	STEBA France STEBA LABORATORIES LTD.
Information provided by:	STEBA France
ClinicalTrials.gov Identifier:	NCT00284908

Purpose

S-Tenatoprazole-Na (STU-Na), a new drug currently under clinical development, belongs to a class of drugs, called proton pump inhibitors (PPls). Some PPIs are already commercially available. STU-Na will be used for treatment of acid related diseases (gastroduodenal ulcers, erosive or ulcerative esophagitis due to gastroesophageal reflux disease). This study evaluates the degree of acid suppression by different doses of STU-Na. The degree of acid suppression is considered to be correlated with clinical efficacy.

In this study four dosages of STU-Na (30 mg, 60 mg, 90 mg, and 120 mg) will be tested in each volunteer. First, one of the dosages will be orally administered for five days. Then, a nine to sixteen day period without study drug administration will follow prior to the administration of the next dosage, for again five days. Each volunteer will have a total of four study drug administration periods.

After the last study drug intake in period 1, 2 and 3 pharmacokinetic blood sampling will be done for four days. After the last study drug intake in period 4 pharmacokinetic blood sampling will be done for five days. Pharmacokinetic blood sampling consists of several blood draws over a pre-determined time period. The pharmacokinetic blood sampling measures the medication concentration in the blood at pre-defined time points.

After the last study drug intake in period 1, 2, 3, and 4, gastric acidity will be measured for 24 hours by means of a thin tube that will be inserted into the stomach through the nostril to evaluate the efficacy of the different dosages of STU-Na.

Condition	Intervention	Phase
Esophagitis Gastroesophageal Reflux Stomach Ulcer Duodenal Ulcer	Drug: S-Tenatoprazole-Na (STU-Na)	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Single Blind (Subject), Dose Comparison, Crossover Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Pharmacodynamic Dose-Response of S-Tenatoprazole-Na (STU-Na) 30 mg, 60 mg, 90 mg and 120 mg in Healthy Volunteers

Resource links provided by NLM:

MedlinePlus related topics: GERD

Drug Information available for: Tenatoprazole

U.S. FDA Resources

Further study details as provided by STEBA France:

Primary Outcome Measures:

Intragastric pH recording for 24 hours after 5 days of treatment [ Time Frame: Beginning of the pH recording before the last study drug intake in each period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetic blood sampling at steady state [ Time Frame: Blood sampling begins before the intake of the last study drug in each period and lasts for 96 hours (periods 1 to 3) or 120 hours (period 4) ] [ Designated as safety issue: No ]

Enrollment:	32
Study Start Date:	September 2006
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I STU-Na: Experimental Cross-over study with escalating doses	Drug: S-Tenatoprazole-Na (STU-Na) 30 mg, 60 mg, 90 mg and 120 mg of STU-Na for 5 days every morning

Detailed Description:

S-Tenatoprazole-Na (STU-Na), a new drug currently under clinical development, belongs to a class of drugs, called proton pump inhibitors (PPls). Some PPIs are already commercially available. STU-Na will be used for treatment of acid related diseases (gastroduodenal ulcers, erosive or ulcerative esophagitis due to gastroesophageal reflux disease). This study evaluates the degree of acid suppression by different doses of STU-Na. The degree of acid suppression is considered to be correlated with clinical efficacy.

In this study four dosages of STU-Na (30 mg, 60 mg, 90 mg, and 120 mg) will be tested in each volunteer. First, one of the dosages will be orally administered for five days. Then, a nine to sixteen day period without study drug administration will follow prior to the administration of the next dosage, for again five days. Each volunteer will have a total of four study drug administration periods.

After the last study drug intake in period 1, 2 and 3 pharmacokinetic blood sampling will be done for four days. After the last study drug intake in period 4 pharmacokinetic blood sampling will be done for five days. Pharmacokinetic blood sampling consists of several blood draws over a pre-determined time period. The pharmacokinetic blood sampling measures the medication concentration in the blood at pre-defined time points.

After the last study drug intake in period 1, 2, 3, and 4, gastric acidity will be measured for 24 hours by means of a thin tube that will be inserted into the stomach through the nostril to evaluate the efficacy of the different dosages of STU-Na.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy male volunteers aged 18 to 55 years inclusive
Able to understand the nature of the study and to give written informed consent
Able to communicate well with the investigator himself or his/her representatives
Able not to smoke during each hospitalization
Normal physical examination at the screening visit
Body Mass Index between 18 kg/m² and 35 kg/m² at the screening visit
Normal blood pressure and heart rate measured under standardized conditions at the screening visit after at least 5 minutes of rest in a supine position: SBP within 90 and 140 mmHg, DBP within 40 and 85 mmHg, and HR within 40 to 85 bpm
Normal 12-lead electrocardiogram at screening visit recorded after at least 5 minutes of rest: PR within 120 and 200 ms, QRS below or equal to 120 ms, and QTc below or equal to 440 ms
Laboratory results within the normal ranges or considered not being of clinical relevance by the investigator

Exclusion Criteria:

Vegetarians
Positive to H. pylori by 13C urea breath test or stool antigen test at screening visit
Contra-indication to proton pump inhibitors treatment
Previous participation in a trial with PPIs within 3 months
Current or historical evidence of clinically relevant cardiovascular, neurological, hematological, hepatic, gastrointestinal, renal, pulmonary, endocrinological, metabolic or psychiatric disease
Any other acute or chronic disease which could influence the volunteer's health and/or the study results
Presence or history of malabsorption or any gastrointestinal surgery except appendectomy or hernia repair
Receipt of medication (including 'over the counter' preparations) within two weeks of dosing
Use of enzyme inducers or enzyme inhibitor drugs within the last three months before the first drug administration
Participation in a clinical trial involving receipt of a licensed (marketed) medicinal product or of an unlicensed (investigational) medicinal product within one month before the study
Past or current drug exposure amounting to drug abuse or addiction
Past or current alcohol exposure amounting to alcohol abuse or addiction; (i.e. > 28 units per week for males, where 1 unit = one measure of spirit (25 mL), one glass of wine (125 mL) or ½ pint beer)
Currently smoke >10 cigarettes per day
Donation of blood or any other major blood loss (>500 mL) within three months before the study
Unwilling or unable to comply with the study protocol for any reason or in the opinion of the investigator should not participate in the study
Positive test for hepatitis B surface antigen, hepatitis C antibody, HIV1 or HIV2 antibody at screening
Known allergy or intolerance to lactose
Known allergy or intolerance to any other compound in the study drug or any other closely related compound

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00284908

Locations

United States, Texas
Healthcare Discoveries, Inc.
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

STEBA France

STEBA LABORATORIES LTD.

Investigators

Principal Investigator:	Dennis A Ruff, MD	Healthcare Discoveries Inc.
Study Director:	Patrick Cohen, MD	STEBA France
Study Director:	Christof Kreutz, MD	STEBA France

More Information

Publications:

Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology. 1990 Aug;99(2):345-51.

DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 1999 Jun;94(6):1434-42. No abstract available.

Armstrong D. Review article: gastric pH -- the most relevant predictor of benefit in reflux disease? Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:19-26; discussion 38-9. Review.

Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion. 1992;51 Suppl 1:59-67.

Galmiche JP, Bruley Des Varannes S, Ducrotte P, Sacher-Huvelin S, Vavasseur F, Taccoen A, Fiorentini P, Homerin M. Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life: effects on intragastric pH and comparison with esomeprazole in healthy volunteers. Aliment Pharmacol Ther. 2004 Mar 15;19(6):655-62.

Horn J. The proton-pump inhibitors: similarities and differences. Clin Ther. 2000 Mar;22(3):266-80; discussion 265. Review.

Kakinoki B, Ono C, Yamazaki N, Chikamatsu N, Wakatsuki D, Uchiyama K, Morinaka Y. General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulf inyl]- 1H-imidazo[4,5-b]pyridine. Methods Find Exp Clin Pharmacol. 1999 Apr;21(3):179-87.

Katz PO, Castell DO, Chen Y, Andersson T, Sostek MB. Intragastric acid suppression and pharmacokinetics of twice-daily esomeprazole: a randomized, three-way crossover study. Aliment Pharmacol Ther. 2004 Aug 15;20(4):399-406.

Kromer W, Horbach S, Luhmann R. Relative efficacies of gastric proton pump inhibitors: their clinical and pharmacological basis. Pharmacology. 1999 Aug;59(2):57-77. Review.

Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80.

Revicki DA, Crawley JA, Zodet MW, Levine DS, Joelsson BO. Complete resolution of heartburn symptoms and health-related quality of life in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1999 Dec;13(12):1621-30.

Stedman CA, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther. 2000 Aug;14(8):963-78. Review.

Uchiyama K, Wakatsuki D, Kakinoki B, Takeuchi Y, Araki T, Morinaka Y. The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs. J Pharm Pharmacol. 1999 Apr;51(4):457-64.

Responsible Party:	STEBA France ( Christof Kreutz/Project leader )
Study ID Numbers:	HPD/STU(-Na) 05819N/TU 1.41
Study First Received:	January 31, 2006
Last Updated:	March 21, 2008
ClinicalTrials.gov Identifier:	NCT00284908 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by STEBA France:

S-Tenatoprazole-Na
Pharmacokinetic
intragastric pH recording
dose-response

Study placed in the following topic categories:

Stomach Ulcer
Gastrointestinal Diseases
Ulcer
Omeprazole
Healthy
Intestinal Diseases
Gastroesophageal Reflux
Duodenal Ulcer
Deglutition Disorders

Esophageal Motility Disorders
Esophagitis
Stomach Diseases
Digestive System Diseases
Esophageal Disorder
Esophageal Diseases
Gastroenteritis
Peptic Ulcer
Duodenal Diseases

Additional relevant MeSH terms:

Stomach Ulcer
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Ulcer
Gastrointestinal Agents
Omeprazole
Enzyme Inhibitors
Intestinal Diseases
Gastroesophageal Reflux
Pharmacologic Actions
Duodenal Ulcer
Deglutition Disorders

Esophageal Motility Disorders
Esophagitis
Pathologic Processes
Stomach Diseases
Digestive System Diseases
Therapeutic Uses
Anti-Ulcer Agents
Esophageal Diseases
Gastroenteritis
Peptic Ulcer
Duodenal Diseases

ClinicalTrials.gov processed this record on August 30, 2009