Clinical trial NCT02123927: Safety, Tolerability and Pharmacokinetics of TAK-438 in Healthy Male Participants
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study of the Safety, Tolerability and Pharmacokinetics of TAK-438 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ascending Single Dose Study
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-04-28
Enrollment: 108
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 primary purpose of this study was to evaluate the single dose safety and pharmacokinetics of TAK-438 in healthy Japanese men.

Detailed description: The drug being tested in this study is called TAK-438. TAK-438 is being tested to find a safe and well-tolerated dose and to assess how TAK-438 moves throughout the body. This study will look at lab results and side effects in people who took TAK-438. This study consisted of 2 sequential studies: a single rising dose study (Steps 1 to 7) and a food-effect study (Steps 8 and 9).

The study population for Steps 1 to 7 consisted of 12 participants; with 9 participants randomized to receive a single dose of TAK-438, and 3 participants to receive placebo. Participants in Steps 1 to 7 received a single dose of study drug after a 10-hour fast. The starting dose was 1 mg followed by administrations of 5, 10, 20, 40, 80, and 120 mg. Steps 8 and 9 consisted of 12 participants in a 2-sequence, 2-period crossover design. Four participants were to receive a single dose of TAK-438 and 2 participants were to receive a single dose of placebo on Day 1, in the fasted state, and 4 participants were to receive a single dose of TAK-438 and 2 participants were to receive a single dose of placebo on Day 1 in the fed state, followed by a second single dose of TAK-438 or placebo in the alternative fed state after a 13 day minimum washout period. Participants in Steps 8 randomized to receive TAK-438 will receive 10 mg and participants in Step 9 will receive 40 mg.

This single-centre trial was conducted in Japan. The overall time to participate in this study was up to 32 days depending on the Step assignment. Participants made 3 to 5 visits to the clinic, including one or two 8-day periods of confinement to the clinic, also depending on Step assignment. All participants made a final visit 15 days after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Japanese healthy adult male volunteer.
2. Is between 20 and 45 years old when giving their informed consent.
3. Is able to understand the consents of the study and to follow them.
4. Provides their written informed consent prior to their participation in this study.
5. Weighs at least 50 kg and has a body mass index (BMI) of 18.5 to 25.0 kg/m\^2 at screening.
6. Has negative results for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, and serological tests for syphilis.
7. Participant whom the investigator or subinvestigator judged to be eligible on the basis of subjective symptoms, objective findings, vital signs, electrocardiogram (ECG) findings, and results of laboratory tests obtained until before the study drug administration.

Exclusion Criteria:

1. Has undergone upper gastrointestinal resectioning or vagotomy.
2. Has hypoacidity or anacidity: intragastric pH ≥ 5.5 at X-ray fluoroscopic confirmation of detained position of a pH probe inserted to measure baseline intragastric pH values.
3. Has a history of previous and current acid-related diseases including reflux esophagitis, gastric ulcer, duodenal ulcer, non-erosive gastroesophageal reflux disease, Barrett's esophagitis or Zollinger-Ellison syndrome.
4. Is undergoing H. pylori eradication within 6 months before the initiation of the study drug administration.
5. Has an inappropriate history of previous and current diseases for study participation including hepatic or renal disorders, and cardiovascular, hematological, endocrine, metabolic, pulmonary, gastrointestinal, neurological, urological, immunological, or psychological diseases.
6. Has a history of drug and food allergy.
7. Has a history of illegal drug abuse or alcoholism within 5 years before the initiation of the study drug administration.
8. Has peripheral vessels being difficult.
9. Has undergone whole blood drawing of at least 200 mL within 4 weeks or 400 mL within 12 weeks prior to initiation of the study drug administration.
10. Has undergone whole blood drawing of at least 800 mL in total within 52 weeks prior to initiation of the study drug administration.
11. Has undergone apheresis drawing \[plasma (including platelet poor plasma or platelet rich plasma) and platelet component collection\] within 2 weeks prior to initiation of the study drug administration.
12. Is taking any prescriptions or over the counter (OTC) drugs within 4 weeks prior to the study drug administration.
13. Has taken any vitamins, herbal medicines, and supplements including St. John's wort, Ginseng, kava kava, ginkgo biloba, melatonin within 4 weeks prior to initiation of the study drug administration.
14. Has had grapefruit (juice and pulp), or caffeine- or alcohol-containing foods or drinks within 72 hr prior to initiation of the study drug administration.
15. Has received other study drugs within 16 weeks prior to initiation of the study drug administration.
16. Participants whom the investigator or subinvestigator judged to be ineligible for study participation.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent 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: Change from Baseline 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(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to hour 48 for TAK-438 and TAK-438 metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438 and TAK-438 metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
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
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
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
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Cmax: Maximum Observed Plasma Concentration TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
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
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Terminal Elimination Rate Constant (λz) for TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Terminal Elimination Half-life (T1/2) for TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438F
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
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
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: MRT: Mean Residence Time for TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose (0 hours) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, and 48 hours postdose
measure: Cumulative Urinary Excretion Ratio for TAK-438F and TAK-438F metabolites M-I and M-II
timeFrame: Day 1 predose and 0-6, 6-12, 12-24, 24-36 and 36-48 hours postdose
Secondary outcomes:
measure: 24-Hour Intragastric pH Profile
timeFrame: Baseline and Day 1
measure: Total Amount of Serum Gastrin
timeFrame: Baseline at prospective time of dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post prospective dose and Day 1 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose
measure: Total Amount of Serum Pepsinogen I
timeFrame: Baseline at prospective time of dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post prospective dose and Day 1 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose
measure: Total Amount of Serum Pepsinogen Ii
timeFrame: Baseline at prospective time of dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post prospective dose and Day 1 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: