TAK-438 Bismuth Drug Interaction Study

A Phase 1, Double-Blind, Parallel Group Study to Evaluate the Safety and Pharmacokinetics of Quadruple Therapy (Bismuth, Clarithromycin, and Amoxicillin) With TAK-438 Versus Quadruple Therapy With Lansoprazole

To evaluate the safety, tolerability, and pharmacokinetics (PK) of quadruple therapy with bismuth, clarithromycin, amoxicillin, and TAK-438 versus quadruple therapy with bismuth, clarithromycin, amoxicillin, and lansoprazole.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori
• Intervention / Treatment: Drug: Clarithromycin; Drug: Amoxicillin; Drug: Tripotassium bismuth dicitrate; Drug: Lansoprazole; Drug: TAK-438

Detailed Description

This is a phase 1, double-blind, parallel group study in participants with Helicobacter pylori (HP positive) who are, additionally, cytochrome P-450 (CYP)2C19 extensive metabolizers (EM) to evaluate the safety, tolerability and pharmacokinetics (PK) of a quadruple therapy with bismuth, clarithromycin, amoxicillin, and TAK-438 versus quadruple therapy with bismuth, clarithromycin, amoxicillin, and lansoprazole. The study will enroll 30 participants.

The treatment phase consists of quadruple therapy twice daily (BID) with tripotassium bismuth dicitrate (600 mg), clarithromycin (500 mg), amoxicillin (1000 mg), and TAK-438 (20 mg) (Group B) or quadruple therapy BID with tripotassium bismuth dicitrate (600 mg), clarithromycin (500 mg), amoxicillin (1000 mg),and lansoprazole (30 mg) (Group A) from Days 1 to 14. Participants will be discharged on Day 15 after final PK blood samples are collected and all procedures performed.

This single-center will be conducted in Korea. Participants will remain confined to the study site from check-in (Day -1) through Day 15 and will followed up through call on Day 17 and return on Day 42 for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HP positive participants.
2. Has body mass index between greater than (>) 18 and less than equal to (<=) 30 kilogram per square meter (kg/m^2) and weighs greater than equal to (>=) 50 kilogram (kg).
3. Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1) until the Follow-up call on Day 17.

Exclusion Criteria:

1. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
2. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of 21 units or more units per week) at any time prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study (up to Day 17).
3. Has history of gastroesophageal reflux disease (GERD), symptomatic GERD, erosive esophagitis, duodenal ulcer, gastric ulcer, Barrett's esophagus, or Zollinger-Ellison syndrome.
4. Has undergone therapeutic upper gastrointestinal endoscopic therapy (example, endoscopic hemostasis or excision including biopsy) within 30 days prior to Screening.
5. Has undergone major surgical procedures within the past 1 month or are scheduled to undergo surgical procedures that may affect gastric acid secretion (example, abdominal surgery, vagotomy, or craniotomy).
6. Has a history of cancer, except basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin that has been in remission for at least 5 years prior to Day 1.
7. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen at Screening.
8. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to Check-in. Cotinine test is positive at Screening or Check-in.
9. Has poor peripheral venous access. Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Day 1.
10. Has abnormal Screening or Check-in laboratory values that suggest a clinically significant underlying disease or subject with the following laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin > the upper limit of normal (ULN).
11. Has reduced renal function assessed by having an estimated glomerular filtration rate <90 milliliter per min per 1.73 square meter (mL/min/1.73 m^2) (as estimated by Chronic Kidney Disease-Epidemology Collaboration) at Screening or Check-in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clarithromycin + Amoxicillin + Bismuth + Lansoprazole; Clarithromycin 500 milligram (mg), tablets, orally, twice daily, along with amoxicillin 1000 mg capsules, orally, twice daily, tripotassium bismuth dicitrate 600 mg, tablets, orally, twice daily, and lansoprazole 30 mg, capsules, orally, twice daily on Days 1 to 14.	Drug: Clarithromycin; Clarithromycin tablets; Drug: Amoxicillin; Amoxicillin capsules; Drug: Tripotassium bismuth dicitrate; Tripotassium bismuth dicitrate tablets; Drug: Lansoprazole; Lansoprazole capsules
Experimental: Clarithromycin + Amoxicillin + Bismuth + TAK-438; Clarithromycin 500 mg, tablets, orally, twice daily, along with amoxicillin 1000 mg, capsules, orally, twice daily, tripotassium bismuth dicitrate 600 mg, tablets, orally, twice daily, and TAK-438 20 mg, tablets, orally, twice daily on Days 1 to 14.	Drug: Clarithromycin; Clarithromycin tablets; Drug: Amoxicillin; Amoxicillin capsules; Drug: Tripotassium bismuth dicitrate; Tripotassium bismuth dicitrate tablets; Drug: TAK-438; TAK-438 tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	Baseline up to Day 17
Percentage of Participants Who Discontinue Due to an Adverse Event (AE)	Baseline up to Day 17
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	Baseline up Day 15
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Baseline up to Day 15
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose	Baseline up to Day 15
Cmax: Maximum Observed Plasma Concentration for Bismuth	Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Bismuth	Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose
Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval for Bismuth	Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2016
• Primary Completion (Actual): April 17, 2017
• Study Completion (Actual): May 11, 2017

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 2, 2016
• First Posted (Estimate): September 8, 2016

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Antacids; Dexlansoprazole; Lansoprazole; Amoxicillin; Clarithromycin; Bismuth
• Other Study ID Numbers: TAK-438_115; U1111-1179-5816 (Other Identifier: WHO); 02892409 (Registry Identifier: ClinicalTrials.gov)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No