Gastroesophageal Reflux Disease (GERD) Clinical Trial
— TAK-438_107Official title:
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
Verified date | May 2014 |
Source | Takeda |
Contact | n/a |
Is FDA regulated | No |
Health authority | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Study type | Interventional |
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of TAK-438 in healthy, non-Japanese men male subjects following a randomized, double blind, placebo controlled, sequential panel, multiple-dose schedule.
Status | Completed |
Enrollment | 48 |
Est. completion date | February 2009 |
Est. primary completion date | February 2009 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 45 Years |
Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
Country | Name | City | State |
---|---|---|---|
United Kingdom | Hammersmith Medicines Research | London |
Lead Sponsor | Collaborator |
---|---|
Takeda |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | (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 | No |
Primary | 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 | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | Days 1 and 7 | No |
Primary | 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 | 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 | No |
Primary | Cmax: Maximum Observed Plasma Concentration for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul | 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 | No |
Primary | 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 | Day 7 | No | |
Primary | 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 | Day 7 | No | |
Primary | (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 | (Cmax-Cmin)/Cavg, where Cmin is the minimum observed plasma concentration and Cavg is the average plasma concentration at steady state. | Day 7 | No |
Primary | 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 to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | Days 1 and 7 | No |
Primary | Terminal Elimination Rate Constant (?z) for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul | Terminal elimination rate constant (?z) is the rate at which drugs are eliminated from the body. | Days 1 and 7 | No |
Primary | 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 | 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 | No |
Primary | Apparent Clearance (CL/F) Pharmacokinetic Parameter for TAK-438 | 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 | No |
Primary | Apparent Volume of Distribution (Vz/F) for TAK-438 | 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 ?z. | Days 1 and 7 | No |
Primary | 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 | 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 | No |
Primary | 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 | 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 | No |
Primary | Renal Clearance (CLr) for TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul | 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 | No |
Primary | Fraction of TAK-438 and TAK-438 metabolites M-I, M-II, M-III and M-IV-Sul 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. | Day 1 and Day 7 | No |
Primary | 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. | Baseline up to Day 9 | Yes |
Primary | 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 (oral temperature), sitting blood pressure (after sitting for 5 minutes), and pulse (bpm). | Baseline up to Day 9 | Yes |
Primary | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | 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 | Yes |
Primary | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Laboratory tests for hematology, serum chemistries, coagulation tests, and urinalysis will be performed. | Baseline up to Day 9 | Yes |
Primary | 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 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 | Yes |
Primary | Safety of TAK-438 | Assessed by physical examination, ECG, and safety tests of blood/urine | 3 months | Yes |
Primary | Tolerability of TAK-438 | Assessed by adverse events | 3 months | Yes |
Primary | Pharmacokinetic analysis of plasma TAK-438 concentrations | 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 | Yes |
Primary | Pharmacodynamic measurement for assay of gastric pH, measurement of gastrin, pepsinogen I, pepsinogen II and the pepsinogen I/II ratio in plasma samples | 3 months | Yes | |
Secondary | Percentage of Time the pH is Greater than pH 4 and 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 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 | No |
Secondary | Percentage of Time the pH is Greater than pH 4 and pH 5 over a 48 Hour Period | 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 | No |
Secondary | Percentage of Time the PH is Greater than pH 4 and 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 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 | No |
Secondary | Total Amount of Gastrin in Plasma | Predose Days 1 through 7 and Days 8 and 9 | No | |
Secondary | Total Amount of Pepsinogen I in Plasma | Predose Days 1 through 7 and Days 8 and 9 | No | |
Secondary | Total Amount of Pepsinogen II in Plasma | Predose Days 1 through 7 and Days 8 and 9 | No | |
Secondary | Pepsinogen I/II Ratio in Plasma | Predose Days 1 through 7 and Days 8 and 9 | No |
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