CClinicalTrials.gg
Sign In
CompletedNCT02123927Updated Apr 28, 2014

Safety, Tolerability and Pharmacokinetics of TAK-438 in Healthy Male Participants

A Phase 1 interventional study of TAK-438 and Placebo in Ascending Single Dose Study, sponsored by Takeda. Completed. Open to male participants aged 20 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-04-28.

Sponsored by Takeda · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
108
Allocation
Randomized
Ages
20 Years to 45 Years
Sex
Male
01

Study summary

The primary purpose of this study was to evaluate the single dose safety and pharmacokinetics of TAK-438 in healthy Japanese men.

Read the 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.

02

Conditions studied

  • Ascending Single Dose Study

Keywords

  • Drug therapy
03

In context

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
108 participants (actual)

Study arms

  • Experimental
    Step 1: TAK-438 1 mg

    TAK-438 1 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 2: TAK-438 5 mg

    TAK-438 5 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 3: TAK-438 10 mg

    TAK-438 10 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 4: TAK-438 20 mg

    TAK-438 20 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 5: TAK-438 40 mg

    TAK-438 40 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 6: TAK-438 80 mg

    TAK-438 80 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Experimental
    Step 7: TAK-438 120 mg

    TAK-438 120 mg, tablets, orally, once on Day 1.

    Drug: TAK-438

  • Placebo comparator
    Steps 1-7: Placebo

    TAK-438 placebo-matching tablets, orally, once on Day 1.

    Drug: Placebo

  • Experimental
    Step 8A: TAK-438 10 mg

    TAK-438 10 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 10 mg, tablets, orally, under fed conditions, once on Day 1, Period 2.

    Drug: TAK-438

  • Experimental
    Step 8 B: TAK-438 10 mg

    TAK-438 10 mg, tablets, orally, under fed conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 10 mg, tablets, orally, under fasted conditions, once on Day 1, Period 2.

    Drug: TAK-438

  • Experimental
    Step 9A: TAK-438 40 mg

    TAK-438 40 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 40 mg, tablets, orally, under fed conditions, once on Day 1, Period 2.

    Drug: TAK-438

  • Experimental
    Step 9B: TAK-438 40 mg

    TAK-438 40 mg, tablets, orally, under fed conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 40 mg, tablets, orally, under fasted conditions, once on Day 1, Period 2.

    Drug: TAK-438

  • Placebo comparator
    Steps 8 (A & B) and 9 (A & B): Placebo

    TAK-438 placebo-matching tablets, orally, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 placebo-matching tablets, orally, once on Day 1, Period 2.

    Drug: Placebo

Interventions

  • DrugTAK-438

    TAK-438 tablets

  • DrugPlacebo

    TAK-438 placebo-matching tablets

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (AE)

    Treatment-emergent 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 through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

    Time frame: Day 1 to Day 15

  2. Number of Participants With Potentially Clinically Significant Vital Sign Findings

    Participants with at least one potentially clinically significant post-baseline vital sign finding. Vital signs included blood pressure, pulse, respiratory rate, and body temperature (armpit), body weight, and body mass index (BMI).

    Time frame: Day 1 to Day 15

  3. Change from Baseline in Body Weight

    Time frame: Day 1 to Day 15

  4. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings

    Time frame: Day 1 to Day 15

  5. Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings

    Laboratory tests for hematology, biochemistry, coagulation and urinalysis were be performed.

    Time frame: Day 1 to Day 15

  6. 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

    AUC(0-48) is a measure of the area under the plasma concentration-time curve from time 0 to 48 hours, calculated using the linear trapezoidal rule.

    Time frame: 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

  7. 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

    (AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC\[0-tlqc\]).

    Time frame: 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

  8. 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

    AUMC(0-tlqc) is a measure of the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

    Time frame: 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

  9. 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

    MRT(0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT(0-tlqc)=AUMC(0-tlqc)/AUC(0-tlqc).

    Time frame: 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

  10. Cmax: Maximum Observed Plasma Concentration TAK-438F and TAK-438F metabolites M-I and M-II

    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

    Time frame: 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

  11. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and TAK-438F metabolites M-I and M-II

    Time to reach the maximum plasma concentration (Tmax), equal to time (hours) to Cmax.

    Time frame: 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

  12. 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

    AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

    Time frame: 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

  13. Terminal Elimination Rate Constant (λz) for TAK-438F and TAK-438F metabolites M-I and M-II

    Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.

    Time frame: 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

  14. Terminal Elimination Half-life (T1/2) for TAK-438F and TAK-438F metabolites M-I and M-II

    Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

    Time frame: 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

  15. Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438F

    CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.

    Time frame: 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

  16. 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

    AUMC(0-inf) is a measure of the area under the first moment plasma concentration-time curve from time 0 to infinity, calculated as AUMC(0-tlqc) + lqc x tlqc/λz + lqc/λz\^2.

    Time frame: 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

  17. MRT: Mean Residence Time for TAK-438F and TAK-438F metabolites M-I and M-II

    Mean residence time, calculated as MRT=AUMC(0-inf)/AUC(0-inf).

    Time frame: 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

  18. Cumulative Urinary Excretion Ratio for TAK-438F and TAK-438F metabolites M-I and M-II

    The cumulative urinary excretion ratio is defined as the percentage of the dose excreted in the urine.

    Time frame: Day 1 predose and 0-6, 6-12, 12-24, 24-36 and 36-48 hours postdose

Secondary outcomes

  1. 24-Hour Intragastric pH Profile

    To obtain intragastric pH a portable pH measuring device with a miniature glass electrode that was calibrated using standard pH 4 and pH 7 solutions was placed in the stomach transnasally and its positioned confirmed by X-ray guidance. pH data was recorded electronically 8:30 AM to 9:10 AM of the following day every 10 seconds.

    Time frame: Baseline and Day 1

  2. Total Amount of Serum Gastrin

    Time frame: 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

  3. Total Amount of Serum Pepsinogen I

    Time frame: 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

  4. Total Amount of Serum Pepsinogen Ii

    Time frame: 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

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 28, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02123927
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Apr 28, 2014
Start date
Sep 2007
Primary completion
Dec 2007
Completion
Dec 2007
Last update
Apr 28, 2014

Study contacts

Medical Director Clinical Science
study director · Takeda

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2014. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Takeda

Start the discussion