Dose Finding StudyPhase 1NCT02141698
Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects
A Phase 1 study testing TAK-438 and Esomeprazole in people with Dose Finding Study, run by Takeda.
Trial summary
The primary purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of TAK-438 following single or multiple doses of TAK-438 in healthy Western men, to investigate the effect of food on the pharmacokinetics of TAK-438, and to compare the TAK-438 pharmacokinetics of Western with Japanese… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Dose Finding Study
- What is being tested?
- TAK-438 and Esomeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- No sites listed yet
- Study dates
- Oct 2007to Feb 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential-Panel, Ascending Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects
The primary purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of TAK-438 following single or multiple doses of TAK-438 in healthy Western men, to investigate the effect of food on the pharmacokinetics of TAK-438, and to compare the TAK-438 pharmacokinetics of Western with 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. This study looked at the pharmacodynamic and pharmacokinetic properties (how the drug moves throughout the body) of the drug and safety (lab results and side effects) in people who took TAK-438.
This study was designed to consist of 4 sequential substudies: a single rising dose study (Cohorts 1 to 7), a food-effect study (Cohort 8), a multiple rising dose study (Cohorts 9 to 11), and a Japanese bridging study (Cohort 12). However, the protocol was halted during the food effect study (Cohort 8) following the discovery of previously unidentified metabolites and as a result, the multiple rising dose (Cohorts 9-11) and ethnicity (Cohort 12) studies were not carried out.
The study population for each of Cohorts 1 to 7 consisted of 9 subjects; with 6 subjects randomized to receive a single dose of TAK-438, and 3 subjects to receive placebo. Subjects in Cohorts 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, 15, 40, and 30 mg.
In Cohort 8 the plan was to assign 12 participants in a 2-sequence, 2-period crossover design. Six participants were to receive a single dose of TAK-438 on Day 1, in the fasted state, followed by a second single dose of TAK-438 on Day 15 in the alternative fed state. The other 6 participants were to receive the study drug like-wise but in the fed then fasted state.
To investigate the effect of multiple dosing, a further 3 cohorts (Cohorts 9-11), each comprising 12 participants were to be introduced to the protocol following completion of the single rising dose study. A final cohort, Cohort 12, consisting of 24 Western participants and 24 Japanese participants was to be used to assess the effect of TAK-438 and esomeprazole on the safety, tolerability, pharmacokinetics and pH of the stomach between these 2 ethnic groups.
This single-centre trial was conducted in the United Kingdom.
- Conditions
- Dose Finding Study
- Being tested
- TAK-438, TAK-438 Placebo, Esomeprazole
- Keywords
- Drug therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-438Drug
TAK-438 tablets
TAK-438 PlaceboDrug
TAK-438 placebo-matching tablets
EsomeprazoleDrug
Esomeprazole tablets
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: TAK-438 1 mg | Experimental | TAK-438 1 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 2: TAK-438 5 mg | Experimental | TAK-438 5 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 3: TAK-438 10 mg | Experimental | TAK-438 10 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 4: TAK-438 20 mg | Experimental | TAK-438 20 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 5: TAK-438 15 mg | Experimental | TAK-438 15 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 6: TAK-438 40 mg | Experimental | TAK-438 40 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 7: TAK-438 30 mg | Experimental | TAK-438 30 mg, tablets, orally, once on Day 1. Receives: Drug: TAK-438 |
| Cohort 8A: Food-effect | Experimental | TAK-438 20 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 2. Receives: Drug: TAK-438 |
| Cohort 8B: Food-effect | Experimental | TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 1. Receives: Drug: TAK-438 |
| Cohort 9: TAK-438 Multiple Dose 1 | Experimental | TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. Receives: Drug: TAK-438 |
| Cohort 10: TAK-438 Multiple Dose 2 | Experimental | TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. Receives: Drug: TAK-438 |
| Cohort 11: TAK-438 Multiple Dose 3 | Experimental | TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. Receives: Drug: TAK-438 |
| Cohort 12: Ethnic Bridging | Experimental | TAK-438 tablets, dose 1, orally, on Days 1-7 of Period 1, followed by a 4-week washout period followed by TAK-438 tablets, dose 2, orally, Days 1-7 of Period 2, followed by a 4-week washout period, followed by esomeprazole tablets, 40 mg, orally, on Days 1-7 of Period 3. TAK-438 doses to be determined from data collected in Cohorts 9-11. Receives: Drug: TAK-438; Drug: Esomeprazole |
| Cohorts 1-7: Placebo | Placebo comparator | TAK-438 placebo-matching tablets, orally, once on Day 1 Receives: Drug: TAK-438 Placebo |
| Cohorts 9-11: Placebo | Placebo comparator | TAK-438 placebo-matching tablets, orally, once on Day 1, where available, if required. Receives: Drug: TAK-438 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]).
Measured: Day 1
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438 and TAK-438 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.
Measured: Day 1
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 and M-II
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.
Measured: Day 1
Cmax: Maximum Observed Plasma Concentration for TAK-438 and TAK-438 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.
Measured: Day 1
Cmin,ss: Minimum Observed Plasma Concentration at Steady State for TAK-438 and TAK-438 metabolites M-I and M-II
Measured: Day 7
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438 and TAK-438 metabolites M-I and M-II
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Measured: Day 1
Terminal Elimination Rate Constant (λz) for TAK-438 and TAK-438 metabolites M-I and M-II
Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.
Measured: Day 1
Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for TAK-438 and TAK-438 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.
Measured: Day 1
Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438 and TAK-438 metabolites M-I and M-II
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.
Measured: Day 1
Apparent Volume of Distribution (Vz/F) for TAK-438 and TAK-438 metabolites M-I and M-II
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.
Measured: Day 1
Total Amount of Drug Excreted in Urine for TAK-438 and TAK-438 metabolites M-I and M-II
Measured: Day 1
Renal Clearance (CLr) for TAK-438 and TAK-438 metabolites M-I and M-II
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.
Measured: Day 1
Fraction of TAK-438 Excreted in Urine (Fe)
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.
Measured: Day 1
Percentage of the Total Time the pH is Greater than pH 5
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 96-hour period following the administration of study drug.
Measured: Over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug
Percentage of Time the pH is Greater than pH 4 over a 24 Hour Period
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 drug.
Measured: Over a 24-hour period at Baseline and over a 24-hour period following the administration of study drug
Percentage of Time the pH is Greater than pH 5 over a 24 Hour Period.
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 drug.
Measured: Over a 24-hour period at Baseline and over a 24-hour period following the administration of study drug
Total Amount of Gastrin in Plasma
Measured: Baseline and Day 1
Total Amount of Pepsinogen I/II in Plasma
Measured: Baseline and Day 1
Physical Examination Findings
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.
Measured: Baseline up to Day 30
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 will include body temperature (tympanic measurement), sitting blood pressure (BP) (after resting for 5 minutes), and pulse (beats per minute (bpm)).
Measured: Baseline up to Day 30
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Measured: Baseline to Day 30
Number of Participants With Potentially Clinically Significant Telemetry Findings
Measured: Baseline up to Day 30
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Laboratory tests for hematology, serum chemistry and urinalysis will be performed.
Measured: Baseline up to Day 30
Number of Participants With Treatment-Emergent Adverse Events (AEs)
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.
Measured: Baseline up to Day 30
Percentage of Time the pH is Greater than pH 4 from 8PM to 8AM.
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.
Measured: Over a 12-hour period at Baseline and over a 12-hour period between 8PM and 8AM following the administration of study drug
• Percentage of Time the pH is Greater than pH 5 from 8 PM to 8 AM
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.
Measured: Over a 12-hour period at Baseline and over a 12-hour period between 8pm and 8 am following the administration of study drug
• Percentage of the Total Time the pH is Greater than pH 4
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 96-hour period following the administration of study drug.
Measured: Over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2014 (estimated)
- Study startOct 2007
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dose Finding StudyStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Richmond Pharmacology Limited
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141698
- Sponsor's protocol ID
- TAK-438_101
- Other IDs
- 2007-003616-66, U1111-1153-8406
- Status last verified
- May 2014
- First submitted
- 15 May 2014
- Last updated
- 19 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential-Panel, Ascending Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-438 in Healthy Western Male Subjects, Preliminary Food Effect Analysis, and an Ethnic Comparison With Japanese Subjects
- ClinicalTrials.gov ID
- NCT02141698
- Acronym / sponsor ID
- TAK-438_101
- Conditions
- Dose Finding Study
- Keywords
- Drug therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Richmond Pharmacology Limited
- Study start
- Oct 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 19 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of TAK-438 following single or multiple doses of TAK-438 in healthy Western men, to investigate the effect of food on the pharmacokinetics of TAK-438, and to compare the TAK-438 pharmacokinetics of Western with 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. This study looked at the pharmacodynamic and pharmacokinetic properties (how the drug moves throughout the body) of the drug and safety (lab results and side effects) in people who took TAK-438.
This study was designed to consist of 4 sequential substudies: a single rising dose study (Cohorts 1 to 7), a food-effect study (Cohort 8), a multiple rising dose study (Cohorts 9 to 11), and a Japanese bridging study (Cohort 12). However, the protocol was halted during the food effect study (Cohort 8) following the discovery of previously unidentified metabolites and as a result, the multiple rising dose (Cohorts 9-11) and ethnicity (Cohort 12) studies were not carried out.
The study population for each of Cohorts 1 to 7 consisted of 9 subjects; with 6 subjects randomized to receive a single dose of TAK-438, and 3 subjects to receive placebo. Subjects in Cohorts 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, 15, 40, and 30 mg.
In Cohort 8 the plan was to assign 12 participants in a 2-sequence, 2-period crossover design. Six participants were to receive a single dose of TAK-438 on Day 1, in the fasted state, followed by a second single dose of TAK-438 on Day 15 in the alternative fed state. The other 6 participants were to receive the study drug like-wise but in the fed then fasted state.
To investigate the effect of multiple dosing, a further 3 cohorts (Cohorts 9-11), each comprising 12 participants were to be introduced to the protocol following completion of the single rising dose study. A final cohort, Cohort 12, consisting of 24 Western participants and 24 Japanese participants was to be used to assess the effect of TAK-438 and esomeprazole on the safety, tolerability, pharmacokinetics and pH of the stomach between these 2 ethnic groups.
This single-centre trial was conducted in the United Kingdom.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: TAK-438 1 mg | Experimental | Drug: TAK-438TAK-438 1 mg, tablets, orally, once on Day 1. |
| Cohort 2: TAK-438 5 mg | Experimental | Drug: TAK-438TAK-438 5 mg, tablets, orally, once on Day 1. |
| Cohort 3: TAK-438 10 mg | Experimental | Drug: TAK-438TAK-438 10 mg, tablets, orally, once on Day 1. |
| Cohort 4: TAK-438 20 mg | Experimental | Drug: TAK-438TAK-438 20 mg, tablets, orally, once on Day 1. |
| Cohort 5: TAK-438 15 mg | Experimental | Drug: TAK-438TAK-438 15 mg, tablets, orally, once on Day 1. |
| Cohort 6: TAK-438 40 mg | Experimental | Drug: TAK-438TAK-438 40 mg, tablets, orally, once on Day 1. |
| Cohort 7: TAK-438 30 mg | Experimental | Drug: TAK-438TAK-438 30 mg, tablets, orally, once on Day 1. |
| Cohort 8A: Food-effect | Experimental | Drug: TAK-438TAK-438 20 mg, tablets, orally, under fasted conditions, once on Day 1, Period 1, followed by a 13 day washout period, followed by TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 2. |
| Cohort 8B: Food-effect | Experimental | Drug: TAK-438TAK-438 20 mg, tablets, orally, under fed conditions, once on Day 1, Period 1. |
| Cohort 9: TAK-438 Multiple Dose 1 | Experimental | Drug: TAK-438TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. |
| Cohort 10: TAK-438 Multiple Dose 2 | Experimental | Drug: TAK-438TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. |
| Cohort 11: TAK-438 Multiple Dose 3 | Experimental | Drug: TAK-438TAK-438 tablet, orally, fixed dose, on Day 1 and Days 8-14. Dose to be determined from data collected in Cohorts 1-7. |
| Cohort 12: Ethnic Bridging | Experimental | Drug: TAK-438, Drug: EsomeprazoleTAK-438 tablets, dose 1, orally, on Days 1-7 of Period 1, followed by a 4-week washout period followed by TAK-438 tablets, dose 2, orally, Days 1-7 of Period 2, followed by a 4-week washout period, followed by esomeprazole tablets, 40 mg, orally, on Days 1-7 of Period 3. TAK-438 doses to be determined from data collected in Cohorts 9-11. |
| Cohorts 1-7: Placebo | Placebo comparator | Drug: TAK-438 PlaceboTAK-438 placebo-matching tablets, orally, once on Day 1 |
| Cohorts 9-11: Placebo | Placebo comparator | Drug: TAK-438 PlaceboTAK-438 placebo-matching tablets, orally, once on Day 1, where available, if required. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-438TAK-438 tablets | Drug | Cohort 10: TAK-438 Multiple Dose 2, Cohort 11: TAK-438 Multiple Dose 3, Cohort 12: Ethnic Bridging, Cohort 1: TAK-438 1 mg, Cohort 2: TAK-438 5 mg, Cohort 3: TAK-438 10 mg, Cohort 4: TAK-438 20 mg, Cohort 5: TAK-438 15 mg, Cohort 6: TAK-438 40 mg, Cohort 7: TAK-438 30 mg, Cohort 8A: Food-effect, Cohort 8B: Food-effect, Cohort 9: TAK-438 Multiple Dose 1 |
| TAK-438 PlaceboTAK-438 placebo-matching tablets | Drug | Cohorts 1-7: Placebo, Cohorts 9-11: Placebo |
| EsomeprazoleEsomeprazole tablets | Drug | Cohort 12: Ethnic Bridging |
Primary outcome
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
Time frame: Day 1
(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]).
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
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 and M-II
Time frame: Day 1
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.
Cmax: Maximum Observed Plasma Concentration for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration; obtained directly from the plasma concentration-time curve.
Cmin,ss: Minimum Observed Plasma Concentration at Steady State for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 7
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Terminal Elimination Rate Constant (λz) for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.
Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.
Apparent Volume of Distribution (Vz/F) for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
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.
Total Amount of Drug Excreted in Urine for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
Renal Clearance (CLr) for TAK-438 and TAK-438 metabolites M-I and M-II
Time frame: Day 1
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.
Fraction of TAK-438 Excreted in Urine (Fe)
Time frame: Day 1
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.
Percentage of the Total Time the pH is Greater than pH 5
Time frame: Over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug
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 96-hour period following the administration of study drug.
Percentage of Time the pH is Greater than pH 4 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 drug
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 drug.
Percentage of Time the pH is Greater than 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 drug
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 drug.
Total Amount of Gastrin in Plasma
Time frame: Baseline and Day 1
Total Amount of Pepsinogen I/II in Plasma
Time frame: Baseline and Day 1
Physical Examination Findings
Time frame: Baseline up to Day 30
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.
Number of Participants With Potentially Clinically Significant Vital Sign Findings
Time frame: Baseline up to Day 30
Participants with at least one potentially clinically significant post-baseline vital sign finding. Vital signs will include body temperature (tympanic measurement), sitting blood pressure (BP) (after resting for 5 minutes), and pulse (beats per minute (bpm)).
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Time frame: Baseline to Day 30
Number of Participants With Potentially Clinically Significant Telemetry Findings
Time frame: Baseline up to Day 30
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Time frame: Baseline up to Day 30
Laboratory tests for hematology, serum chemistry and urinalysis will be performed.
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Time frame: Baseline up to Day 30
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.
Percentage of Time the pH is Greater than pH 4 from 8PM to 8AM.
Time frame: Over a 12-hour period at Baseline and over a 12-hour period between 8PM and 8AM following the administration of study drug
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.
• Percentage of Time the pH is Greater than pH 5 from 8 PM to 8 AM
Time frame: Over a 12-hour period at Baseline and over a 12-hour period between 8pm and 8 am following the administration of study drug
Using a calibrated gastric pH monitor, the measurement of stomach pH will be made continuously over a 12-hour period at Baseline and over a 12-hour period following the administration of study drug.
• Percentage of the Total Time the pH is Greater than pH 4
Time frame: Over a 24-hour period at Baseline and over a 96-hour period following the administration of study drug
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 96-hour period following the administration of study drug.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-438 and Esomeprazole in people with Dose Finding Study, run by Takeda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Day 1). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2014.