Clinical trial NCT02892409: TAK-438 Bismuth Drug Interaction Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Helicobacter Pylori
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-09-08
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: Baseline up to Day 17
measure: Percentage of Participants Who Discontinue Due to an Adverse Event (AE)
timeFrame: Baseline up to Day 17
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose
timeFrame: Baseline up Day 15
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
timeFrame: Baseline up to Day 15
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose
timeFrame: Baseline up to Day 15
measure: Cmax: Maximum Observed Plasma Concentration for Bismuth
timeFrame: Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose
measure: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Bismuth
timeFrame: Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose
measure: Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval for Bismuth
timeFrame: Day 14 pre-dose and at multiple timepoints (up to 12 hours) post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: