- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02141711
TAK-438 - Safety, Blood Levels & Effects of Repeated Doses (TAK-438_107)
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential-Panel, Multiple Repeat Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Non-Japanese Male Subjects
Study Overview
Status
Intervention / Treatment
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. This study looked at pharmacokinetic (effect of the body on the drug) and pharmacodynamic properties (effect of the drug on the body) as well as look at lab results and side effects in people who took TAK-438. This study was designed as a randomized, sequential-panel, multiple repeat dose study.
The study population consisted of 4 Cohorts with 12 participants in each Cohort; with 9 participants randomized to receive a single dose of TAK-438, and 3 participants to receive placebo. Participants in each Cohort received a single dose of study drug once daily after a 10-hour fast. The starting dose was 10 mg followed by administrations of 20, 40, and 30 mg.
This single-centre trial was conducted in the United Kingdom. The overall time to participate in this study was up to 37 days. Participants made 2 visits to the clinic for screening, one 11-day period of confinement to the clinic, and 2 further visits after the confinement period. All participants were contacted by telephone 7 days after last dose of study drug for a follow-up assessment.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, NW10 7EW
- Hammersmith Medicines Research
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male subjects aged 18 to 45, inclusive, who are in good health, as determined by medical history, physical examination, clinical laboratory evaluations and urine drug screen.
- The subject has the ability to tolerate the pH probe for 24 hours prior to Randomization (Day 1).
Exclusion Criteria:
- Clinically significant history of hypersensitivity to any drug or food or any excipients of TAK-438
- History of gastroesophageal reflux disease (GERD), symptomatic GERD, erosive esophagitis, duodenal ulcer,gastric ulcer, dyspepsia, Barrett's esophagus, or Zollinger-Ellison syndrome
- The subject has a positive test result for Helicobacter pylori at the Initial Screening Visit
- Any clinically significant results from physical examinations or clinical laboratory results as deemed by the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: TAK-438 10 mg
TAK-438 10 mg tablets, orally, once, daily, for 7 days.
|
TAK-438 tablets
|
Experimental: Cohort 2: TAK-438 20 mg
TAK-438 20 mg tablets, orally, once, daily, for 7 days.
|
TAK-438 tablets
|
Experimental: Cohort 3: TAK-438 40 mg
TAK-438 40 mg tablets, orally, once, daily, for 7 days.
|
TAK-438 tablets
|
Experimental: Cohort 4: TAK-438 30 mg
TAK-438 30 mg tablets, orally, once, daily, for 7 days.
|
TAK-438 tablets
|
Placebo Comparator: Cohorts 1-4: Placebo
TAK-438 placebo-matching tablets, orally, once, daily, for 7 days.
|
TAK-438 placebo-matching tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
(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]).
|
Days 1 and 7
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
|
Days 1 and 7
|
AUC(0-tau): Area Under the Plasma Concentration-time Curve from Time 0 to Time tau Over the Dosing Interval for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
AUC(0-tau) is a measure of the area under the plasma concentration-time curve from time 0 to time tau over a dosing interval, where tau is the length of the dosing interval.
|
Days 1 and 7
|
Cmax: Maximum Observed Plasma Concentration for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
|
Days 1 and 7
|
Cmin,ss: Minimum Observed Plasma Concentration at Steady State for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 7
|
Day 7
|
|
Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 7
|
Day 7
|
|
(Cmax-Cmin)/Cavg: Fluctuation of Concentration at Steady State for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 7
|
(Cmax-Cmin)/Cavg, where Cmin is the minimum observed plasma concentration and Cavg is the average plasma concentration at steady state.
|
Day 7
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
|
Days 1 and 7
|
Terminal Elimination Rate Constant (λz) for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.
|
Days 1 and 7
|
Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Days 1 and 7
|
Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
|
Days 1 and 7
|
Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438
Time Frame: Days 1 and 7
|
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.
|
Days 1 and 7
|
Apparent Volume of Distribution (Vz/F) for TAK-438
Time Frame: Days 1 and 7
|
Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz.
|
Days 1 and 7
|
Ae(0-t): Total Amount of Drug Excreted in Urine from Time 0 to Time T for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 1 and Day 7
|
Ae(0-t) is the total amount of drug excreted in urine from time 0 to t, where t is 24 hours on Day 1 and 48 hours on Day 7.
|
Day 1 and Day 7
|
Ae(0-tau): Total Amount of Drug Excreted in Urine from Time 0 to Time tau for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 1 and Day 7
|
Ae(0-tau) is the total amount of drug excreted in urine from time 0 to tau, where tau equals 24 hours.
|
Day 1 and Day 7
|
Renal Clearance (CLr) for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul
Time Frame: Day 1 and Day 7
|
CLr is a measure of apparent clearance of the drug from the urine calculated as total amount excreted in the urine from time 0 to 24 hours postdose / plasma area under the curve from time 0 to 24 hours post-dose.
|
Day 1 and Day 7
|
Fraction of TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul Excreted in Urine (Fe)
Time Frame: Day 1 and Day 7
|
Fe is a measure of the fraction of drug excreted in urine and is calculated as Fe = (total amount excreted in the urine from time 0 to 24 hours post-dose / dose)×100.
|
Day 1 and Day 7
|
Physical Examination Findings
Time Frame: Baseline up to Day 9
|
A baseline physical examination (defined as the pretreatment assessment immediately prior to the start of study drug) will consist of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; (11) genitourinary system; and (12) other.
All subsequent physical examinations should assess clinically significant changes from the baseline examination.
|
Baseline up to Day 9
|
Number of Participants With Potentially Clinically Significant Vital Sign Findings
Time Frame: Baseline up to Day 9
|
Participants with at least one potentially clinically significant post-baseline vital sign finding.
Vital signs will include body temperature (oral temperature), sitting blood pressure (after sitting for 5 minutes), and pulse (bpm).
|
Baseline up to Day 9
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Time Frame: Baseline to Day 9
|
Full 12-lead ECGs will be recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (using Bazett correction; QTcB) intervals.
The investigator or other qualified physician will interpret each ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.
|
Baseline to Day 9
|
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Time Frame: Baseline up to Day 9
|
Laboratory tests for hematology, serum chemistries, coagulation tests, and urinalysis will be performed.
|
Baseline up to Day 9
|
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Time Frame: Baseline up to Day 9
|
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 7 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
|
Baseline up to Day 9
|
Safety of TAK-438
Time Frame: 3 months
|
Assessed by physical examination, ECG, and safety tests of blood/urine
|
3 months
|
Tolerability of TAK-438
Time Frame: 3 months
|
Assessed by adverse events
|
3 months
|
Pharmacokinetic analysis of plasma TAK-438 concentrations
Time Frame: 3 months
|
Primary pharmacokinetic parameters (AUC (0-tlqc), AUC (0-inf), Cmax) for TAK-438 and its metabolites M-I, M-II, M-III and M-IV-Sul will be subject to statistical analysis
|
3 months
|
Pharmacodynamic measurement for assay of gastric pH, measurement of gastrin, pepsinogen I, pepsinogen II and the pepsinogen I/II ratio in plasma samples
Time Frame: 3 months
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Time the pH is Greater than pH 4 and pH 5 over a 24 Hour Period
Time Frame: Over a 24-hour period at Baseline and over a 24-hour period following the administration of study on Days 1, 4 and 7
|
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 24-hour period at Baseline and over a 24-hour period following the administration of study on Days 1, 4 and 7.
|
Over a 24-hour period at Baseline and over a 24-hour period following the administration of study on Days 1, 4 and 7
|
Percentage of Time the pH is Greater than pH 4 and pH 5 over a 48 Hour Period
Time Frame: Over a 48-hour period following the administration of study on Day 7
|
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 48-hour period following the administration of study drug on Day 7.
|
Over a 48-hour period following the administration of study on Day 7
|
Percentage of Time the PH is Greater than pH 4 and pH 5 from 8 PM to 8 AM
Time Frame: Over a 12-hour period from 8 PM to 8 AM on Days 1, 4 and 7
|
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period from 8 PM to 8 AM to assess nocturnal pH.
|
Over a 12-hour period from 8 PM to 8 AM on Days 1, 4 and 7
|
Total Amount of Gastrin in Plasma
Time Frame: Predose Days 1 through 7 and Days 8 and 9
|
Predose Days 1 through 7 and Days 8 and 9
|
|
Total Amount of Pepsinogen I in Plasma
Time Frame: Predose Days 1 through 7 and Days 8 and 9
|
Predose Days 1 through 7 and Days 8 and 9
|
|
Total Amount of Pepsinogen II in Plasma
Time Frame: Predose Days 1 through 7 and Days 8 and 9
|
Predose Days 1 through 7 and Days 8 and 9
|
|
Pepsinogen I/II Ratio in Plasma
Time Frame: Predose Days 1 through 7 and Days 8 and 9
|
Predose Days 1 through 7 and Days 8 and 9
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TAK-438_107
- U1111-1153-8443 (Other Identifier: World Health Organization)
- 2008-004975-22 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastroesophageal Reflux Disease (GERD)
-
Vanderbilt University Medical CenterCompletedGastroesophageal Reflux Disease (GERD) | Non-erosive Reflux Disease (NERD)United States
-
University of North Carolina, Chapel HillNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedGastroesophageal Reflux Disease | GERD | Acid Reflux | RefluxUnited States
-
Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI)CompletedGastroesophageal Reflux Disease (GERD) | RefluxUnited States, Canada
-
Torax Medical IncorporatedCompletedGERD Gastroesophageal Reflux DiseaseUnited States
-
Wake Forest University Health SciencesTakedaCompletedGastroesophageal Reflux Disease (GERD)United States
-
AstraZenecai3 InnovusCompletedGastroesophageal Reflux Disease (GERD)United States
-
NDO Surgical, Inc.TerminatedGastroesophageal Reflux Disease (GERD)United States, Belgium, Germany
-
NDO Surgical, Inc.CompletedGastroesophageal Reflux Disease (GERD)United States, Canada
-
Implantica CE Reflux Ltd.RecruitingGastroesophageal Reflux Disease (GERD)Switzerland, Germany
-
Dexa Medica GroupTerminatedGastroesophageal Reflux Disease (GERD)Indonesia
Clinical Trials on TAK-438
-
TakedaCompletedJapanese Healthy Adult MaleJapan
-
TakedaCompleted
-
TakedaCompleted
-
TakedaCompletedErosive EsophagitisJapan
-
TakedaCompletedAscending Single Dose Study
-
TakedaCompletedNon-erosive Gastroesophageal Reflux DiseaseJapan
-
TakedaCompletedNon-erosive Gastroesophageal Reflux DiseaseJapan
-
TakedaCompletedGastric Ulcer, Duodenal Ulcer, and Reflux EsophagitisJapan
-
TakedaCompleted