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This will be a randomized, placebo-controlled, single, oral dose, four-way Williams crossover study design in healthy male and female subjects. The study consists of screening (28 days), treatment (1 day/dosing session) and follow-up (7 to 14 days) period and the total duration of study participation for each subject will be approximately 9 weeks. Each subject will participate in 4 dosing sessions separated by a minimum 7-day washout period. All subjects will receive single doses of retosiban 100 mg, (treatment A) retosiban 800 mg (Treatment B), moxifloxacin 400 mg (Treatment C) and placebo (Treatment D) in one of the four treatment sequences (ABDC, BCAD, CDBA, DACB) following a Williams design Twelve-lead ECGs and continuous Holter monitoring, clinical laboratory safety tests, vital sign measurements, physical examinations, adverse event reports, and pharmacokinetic samples will be collected throughout the study. In each study period, cardiac conduction will be measured using a 24-hour continuous 12-lead Holter monitor from the morning of Day 1 (dosing) until the morning of Day 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retosiban 100 mg | Experimental | Each subject will be randomized to single dose of retosiban 100 mg in one of the four treatment sequences. |
|
| Retosiban 800 mg | Experimental | Each subject will be randomized to single dose of retosiban 800 mg in one of the four treatment sequences |
|
| Placebo | Placebo Comparator | Each subject will be randomized to single dose of matching placebo in one of the four treatment sequences |
|
| Moxifloxacin 400 mg | Active Comparator | Each subject will be randomized to single dose of moxifloxacin 400 mg in one of the four treatment sequences |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Retosiban 100 mg | Drug | Subjects will be administered with single dose of one moxifloxacin placebo tablet, one 100 mg tablet of retosiban and 7 retosiban matched placebo tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in QT duration corrected for heart rate by Fridericia's formula (QTcF) interval at each timepoint for retosiban as compared with time-matched placebo | Single 12-lead electrocardiograms (ECG)s will be obtained at each timepoint during the study using an ECG machine that automatically calculates corrected QT interval (QTc) interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading. | Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in QTcF, QT duration corrected for heart rate by Bazett's formula (QTcB), and QT interval corrected for heart rate (QTci) /QTciL interval at each timepoint for 100 mg and 800 mg retosiban as compared with time-matched placebo | Single 12-lead ECGs will be obtained for subjects receiving 100 mg and 800 mg retosiban at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26138866 | Derived | Stier B, Fossler M, Liu F, Caltabiano S. Effect of Retosiban on Cardiac Repolarization in a Randomized, Placebo- and Positive-controlled, Crossover Thorough QT/QTc Study in Healthy Men and Women. Clin Ther. 2015 Jul 1;37(7):1541-54. doi: 10.1016/j.clinthera.2015.05.007. Epub 2015 Jun 29. |
| Label | URL |
|---|---|
| Results for study 113789 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 113789 | Individual Participant Data Set | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| Retosiban 800 mg | Drug | Subjects will be administered with single dose of one moxifloxacin placebo tablet and eight 100 mg tablets of retosiban |
|
| Placebo | Drug | Subjects will be administered with one moxifloxacin placebo tablet and eight retosiban matched placebo tablets |
|
| Moxifloxacin 400 mg | Drug | Subjects will be administered with one 400 mg moxifloxacin tablet and eight retosiban matched placebo tablets |
|
| Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session. |
| Change from baseline in QTcF, QTcB, and QTci/QTciL interval at each timepoint for moxifloxacin as compared with time-matched placebo | Single 12-lead ECGs will be obtained for subjects receiving moxifloxacin at each timepoint during the study using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Change = 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading. | Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session. |
| Plasma concentrations of retosiban and GSK2847065 | Pharmacokinetic data will include plasma concentration of retosiban and GSK2847065 | Day 1 (pre-dose), 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose and Day 2 per dosing session. |
| Maximum observed concentration (Cmax) for retosiban and GSK2847065 | Pharmacokinetic data will include Cmax of retosiban and GSK2847065 | Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session |
| Time to maximum concentration (tmax) for retosiban and GSK2847065 | Pharmacokinetic data will include tmax of retosiban and GSK2847065 | Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session |
| Area under the concentration-time curve over the dosing interval (AUC(0-τ)) for retosiban and GSK2847065 | Pharmacokinetic data will include AUC0-τ of retosiban and GSK2847065 | Day 1 (pre-dose, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose) and Day 2 per dosing session |
| Maximal change from baseline for QTcF and QTcB | Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates QTc interval. An average of at least 3 12-lead Holter ECG replicates per time point. Maximal Change from baseline = maximum 12-lead ECG reading at each timepoint minus the baseline 12-lead ECG reading | Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session |
| Change from baseline for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate at each timepoint | Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. Change from baseline for other cardiac electrophysiological will be calculated as: other cardiac electrophysiological parameters at each timepoint minus baseline value | Baseline (Day 1-pre-dose) and 1 hour [hr], 8 hrs, 12 hrs , 24 hrs (Day 2) post-dose and Day 7 per dosing session |
| Safety and tolerability of retosiban as assessed by change from baseline in 12-lead ECGs | Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals | Day 1 (pre-dose, 1 hr, 8 hr, 12 hr post-dose), Day 2 and Day 7 |
| Safety and tolerability of retosiban as assessed by change from baseline in systolic and diastolic blood pressure | Vital sign measurements will be done in supine position and will include systolic and diastolic blood pressure | Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7 |
| Safety and tolerability of retosiban as assessed by change from baseline in pulse rate | Vital sign measurements will be done in supine position and will include pulse rate. | Day 1 (pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 18 hr post-dose), Day 2 and Day 7 |
| Safety and tolerability of retosiban as assessed number of adverse events | Safety and tolerability parameters will include recording of AEs, throughout the study | 9 weeks |
| Safety and tolerability of retosiban as assessed by change from baseline in clinical laboratory tests | Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters | Day -1 and Day 2 and Day 7 |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 113789 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C522194 | GSK221149A |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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