Clinical trial NCT02123953: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-438 in Healthy Male Participants
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-438 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dose Finding Study
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-04-28
Enrollment: 60
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the safety and pharmacokinetics of TAK-438 following multiple oral doses to healthy adult Japanese male participants

Detailed description: The drug being tested in this study is called TAK-438. TAK-438 was being tested to assess side effects and how TAK-438 moves throughout the body after multiple doses have been administered. This study looked at lab results and side effects in people who took TAK-438.

The study consisted of 5 steps covering dose ranges of TAK-438 from 10, 15, 20, 30 and 40 mg once daily for 7 days. The study population for each step included 12 participants. Within each step, 9 participants were randomized to TAK-438 and 3 participants were randomized to placebo. A total of 60 participants were enrolled.

The dosing groups in this study took place in sequential order. Therefore, the TAK-438 15 mg group did not start until the TAK-439 10 mg group had completed, etc. All participants in each dosing group were asked to take the study drug in the morning, after fasting for at least 10 hours, each day throughout the study.

This single-centre trial was conducted in the Japan. The overall time to participate in this study was up to 43 days. Participants made 3 visits to the clinic, including one 11-day period of confinement to the clinic, and a final visit 7 days after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Healthy adult Japanese male volunteer.
2. Is 20-45 years old inclusive, at time of giving consent.
3. Is capable of understanding and complying with protocol requirements.
4. Signs a written, informed consent form prior to the initiation of any study procedure.
5. Weighs at least 50 kg and has a body mass index (BMI) of 18.5 to 25.0 kg/m\^2 inclusive at screening.
6. Tests negative for hepatitis B surface antigen (HBs), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen-antibody and syphilis serum reaction test.
7. The participant who the investigator or subinvestigator confirmed to be eligible to participate in this study based on results of the screening tests, and physical examination, physical findings, vital signs, electrocardiogram (ECG), clinical laboratory tests etc. from 3 days before dosing to before the start of dosing on Day 1 with the study drug.

Exclusion Criteria:

1. Has undergone upper gastrointestinal resectioning or vagetomy.
2. Is judged to have hypoacidity or anacidity.
3. Presently has or a history of acid-related diseases (e.g., erosive esophagitis, duodenal ulcer, gastric ulcer, non-erosive esophagitis, Barrett's esophagitis or Zollinger-Ellison syndrome).
4. Received H. pylori eradication treatment within 6 months prior to the start of treatment with the study drug.
5. Presently has or has a history of hepatic disorder, renal disorder, cardiovascular system disease, blood disease, endocrine disease, metabolic disease, lung disease, gastrointestinal disease, nervous system disease, urological disease, immunological disease or mental illness that makes him not eligible to participate in this study.
6. Presently has or has a history of hypersensitivity or allergy towards 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 treatment with the study drug.
8. Participant for whom it is difficult to collect blood from the peripheral veins.
9. Has donated more than 200 mL of whole blood within 4 weeks (28 days) or more than 400 mL of whole blood within 12 weeks (84 days) prior to the start of treatment with the study drug.
10. Has donated a total volume of more than 800 mL of whole blood within 52 weeks (364 days) prior to the start of treatment with the study drug.
11. Has given plasma component and plaque component within 2 weeks (14 days) prior to the start of treatment with the study drug.
12. Has used a prescription drug (including over-the counter drugs) within 4 weeks (28 days) prior to the start of treatment with the study drug.
13. Has used vitamins, Chinese herbal remedies, or supplement (including St John's Wort, ginseng, kava kava, ginkgo biloba, melatonin) within 4 weeks (28 days) prior to the start of treatment with the study drug.
14. Has ingested any foods or beverages containing grapefruit (juice or pulp), caffeine, alcohol within 72 hours prior to the start of treatment with the study drug.
15. Administered another study drug within 16 weeks (112 days) prior to the start of treatment with this study drug.
16. Administered TAK-438 in the past.
17. Is considered by the investigator or subinvestigator, for any reason, to be an unsuitable candidate for participating in this study

Primary outcomes:
measure: Number of Participants With Adverse Events (AE)
timeFrame: Day 1 to Day 15
measure: Number of Participants With Potentially Clinically Significant Vital Sign Findings
timeFrame: Day 1 to Day 15
measure: Number of Participants With Potentially Clinically Significant Changes in Body Weight
timeFrame: Day 1 to Day 15
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Day 1 to Day 15
measure: Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
timeFrame: Day 1 to Day 15
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve from Time 0 to Time tau Over the Dosing Interval for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: AUMC(0-tlqc): Area Under the First Moment Plasma Concentration-time Curve from Time 0 (t1) to Time of the Last Quantifiable Concentration (tlqc) for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: MRT(0-tlqc): Mean Residence Time from Time 0 (t1) to Time of the Last Quantifiable Concentration (tlqc) for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Terminal Elimination Rate Constant (λz) for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Terminal Elimination Half-life (T1/2) for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Apparent Clearance (CL/F) for TAK-438F
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) for TAK-438F
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: AUMC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: MRT: Mean Residence Time for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 to 7 predose, Days 1 and 7 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours post- dose, and Day 7 24 hours post-dose
measure: Cumulative Urinary Excretion Ratio for TAK-438F and TAK-438F metabolites M-I and M-II, M-III and M-IV-Sul
timeFrame: Days 1 predose, and Days 1 and 7 0-6, 6-12, and 12-24 hours post-dose
Secondary outcomes:
measure: 24-Hour Intragastric pH Profile
timeFrame: Day 1 and Day 7
measure: Total Amount of Serum Gastrin
timeFrame: Predose Days 1 to 7, Day 7 24 hours post-dose, and Day 15
measure: Total Amount of Serum Pepsinogens I
timeFrame: Predose Days 1 to 7, Day 7 24 hours post-dose, and Day 15
measure: Total Amount of Serum Pepsinogens II
timeFrame: Predose Days 1 to 7, Day 7 24 hours post-dose, and Day 15
measure: Pepsinogens I/Pepsinogens II Ratio
timeFrame: Predose Days 1 to 7, Day 7 24 hours post-dose, and Day 15
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Jenkins H, Sakurai Y, Nishimura A, Okamoto H, Hibberd M, Jenkins R, Yoneyama T, Ashida K, Ogama Y, Warrington S. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015 Apr;41(7):636-48. doi: 10.1111/apt.13121. Epub 2015 Feb 23.