Phase 3 Study to Evaluate the Acid-Inhibitory Effect of Multiple Oral Doses of TAK-438

Healthy Clinical Trial

Official title:

Phase 3 Open-Label Crossover Pharamacodynamic Study to Evaluate the Acid-inhibitory Effect of TAK-438 20 mg With Esomeprazole 20 mg or Rabeprazole Sodium 10 mg in Healthy Adult Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02037477
• Other study ID #: TAK-438/CPH-010
• Secondary ID: U1111-1152-3926J
• Status: Completed
• Phase: Phase 3
• First received: January 14, 2014
• Last updated: August 7, 2014
• Start date: January 2014
• Est. completion date: March 2014

Study information

• Verified date: August 2014
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the acid-inhibitory effect of multiple oral doses of TAK-438 and the relative effect of TAK-438 versus two controls (esomeprazole and rabeprazole sodium) in healthy Japanese adult male participants with the CYP2C19 EM genotype.

Description:

This is a Phase 3 open-label crossover study to evaluate the acid-inhibitory effect following 7 days multiple doses of TAK-438 (20 mg per dose) and esomeprazole (20 mg per dose) (Cohort 1) or TAK-438 (20 mg per dose) and rabeprazole sodium (10 mg per dose) (Cohort 2) in healthy Japanese adult male participants (CYP2C19 genotype: EM). There will be a total of 20 subjects, 5 per group for both Cohorts 1 and 2. At least 2 subjects each with the homo EM (*1/*1) or hetero EM (*1/*2, *1/*3) CYP2C19 genotype will be enrolled among the 5 subjects per group.

The drug being tested in this study is called TAK-438. This study will look at the acid inhibitory effect following 7 days multiple doses of TAK-438 and esomeprazole (Cohort 1) or TAK-438 and rabeprazole sodium (Cohort 2) in healthy Japanese adult male participants witrh the CYP2C19 EM genotype.

The study will enroll a total of 20 participants, 5 per group for both Cohorts. At least 2 subjects each with the homo EM (*1/*1) or hetero EM (*1/*2, *1/*3) CYP2C19 genotype will be enrolled among the 5 subjects per group.

• Group A, Cohort 1: TAK-438 (20 mg per dose for 7 days) followed by esomeprazole (20 mg per dose for 7 days)

• Group B, Cohort 1: esomeprazole (20 mg per dose for 7 days) followed by TAK-438 (20 mg per dose for 7 days)

• Group C, Cohort 2: TAK-438 (20 mg per dose for 7 days) followed by rabeprazole sodium (10 mg per dose for 7 days)

• Group D, Cohort 2: rabeprazole sodium (10 mg per dose for 7 days) followed by TAK-438 (20 mg per dose for 7 days).

All participants will be asked to take Study Medication at the same time each day throughout the study. This single center trial will be conducted in Japan. The overall time to participate in this study is 31 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• 1. Is a healthy Japanese adult male volunteer 2. Is aged 20 to 45 years, inclusive, at the time of informed consent. 3. Has been confirmed at CYP2C19 genotyping as an Extensive Metabolizer [EM (*1/*1,*1/*2,*1/*3)] .

4. Capable of understanding and complying with the protocol requirements. 5. The participant signs and dates a written informed consent form prior to the initiation of any study procedures.

6. Weighs 50 kg or more and has BMI of 18.5 or more and less than 25.0 kg/m2 at Screening or admission (Day -3).

7. H. pylori-negative at Screening.

Exclusion Criteria:

• Has undergone resection of the upper gastrointestinal tract or vagotomy. 2. Was determined to have hypoacidity or anacidity 3. Has a present or past history of acid-related disease (reflux esophagitis, gastric ulcer, duodenal ulcer, non-erosive gastroesophageal reflux, Barrett's esophagus, Zollinger-Ellison syndrome, etc.) 4. Has undergone eradication of H. pylori within 6 months prior to the start of the study drug administration.

5. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormalities which may impact the ability of the subject to participate or potentially confound the study results.

6. Has a known hypersensitivities or allergies to drugs or food. 7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the start of the study drug administration.

8. Has poor peripheral venous access. 9. Had 200 mL or more of whole blood drawn within 4 weeks (28 days) prior to the start of the study drug administration or 400 mL or more of whole blood drawn within 12 weeks (84 days) prior to the start of the study drug administration.

10. Had a total volume of 800 mL or more of whole blood drawn within 52 weeks (364 days) prior to the start of the study drug administration.

11. Has undergone blood component draw within 2 weeks (14 days) prior to the start of the study drug administration.

12. Requires treatment with any of the excluded medications specified in the study or requires nutrition with any vitamin supplements or foods prohibited in the study.

13. Has received study medication within 16 weeks (112 days) prior to the start of the study drug administration.

14. Has received TAK-438 in the past. 15. Has a history of cancer. 16. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen or serological reaction for syphilis at Screening.

17. Has a Screening or admission (Day -3) abnormal clinically significant ECG. 18. Has abnormal Screening or admission (Day -3) laboratory values that suggest a clinically significant underlying disease or subject with the following lab abnormalities: ALT or AST > twice the upper limited of the normal range.

19. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.

20. Participant who, in the opinion of the investigator or sub-investigator, is unlikely to comply with the protocol or is unsuitable for any other reasons.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• TAK-438, esomeprazole
TAK-438 tablets, esomeprazole capsules
• Esomeprazole, TAK-438
Esomeprazole capsules, TAK-438 tablets
• TAK-438, rabeprazole sodium
TAK-438 tablets, rabeprazole sodiumu tablets
• Rabeprazole sodium, TAK-438
Rabeprazole tablets, TAK-438 tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intragastric pH time course over 24 hours	Intragastric pH will be measured continuously for 24 hours by pH meter.	At baseline (Day -2 - Day -1), administration period (Days 1 - Day 2 and Days 7 - Day 8)	No
Secondary	Frequency of adverse events	The frequency of adverse events by type, seriousness, time to onset. Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug to the last dose of study drug.	31 days	Yes
Secondary	Change in Vital signs	Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).	At screening, baseline (Day -3, Day -2, Day -1), administration period (Days 1,Day 2,Day 7,Day 8), and post-test (Day 28)	Yes
Secondary	12-lead electrocardiogram (at rest)		At Screening, baseline (Day -3), administration period (Day 8), and post-test (Day 28)	Yes
Secondary	Number of participants with markedly abnormal laboratory values	For clinical laboratory results, summary statistics will be calculated for observed values at baseline and each evaluation time point and for change from baseline for each study medication.	At Screening, baseline (Day -3), administration period (Day 1, Day 8), and post-test (Day 28)	Yes