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This will be a randomized single sequence open label study. This study is designed to determine if chronic dosing with efavirenz (EFZ) will have an effect on the pharmacokinetics (PK) of intravenously-administered retosiban in healthy volunteers. The study consists of screening (28 days), treatment (1 dosing session) and follow-up (7 to 14 days) period, and the total duration of study participation for each subject will be approximately 8 weeks. During the treatment period, subjects will be admitted to the clinical research unit the day before dosing (Day 1) and will remain until completion of the last assessment on Day 20. All subjects will receive on Day 1, a 6 milligrams (mg) bolus of retosiban for 5 minutes (min), followed by a 6 mg/hour (hr) infusion for 12 hrs. On Day 2, a washout day will occur. On Days 3-17, subjects will receive EFZ 600 mg once daily in the evening. On Day 18, subjects will receive a 6 mg bolus of retosiban for 5 mins, followed by a 6 mg/hr infusion for 12 hrs plus a 600 mg dose of EFZ.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retosiban and EFZ | Experimental | All subjects will receive on Day 1, a 6 mg bolus of retosiban for 5 min, followed by a 6 mg/hr infusion for 12 hrs. On Day 2 a washout day will occur. On Days 3-17, subjects will receive EFZ 600 mg OD dose of in the evening. On Day 18, subjects will receive a 6 mg bolus of retosiban for 5 mins, followed by a 6 mg/hr infusion for 12 hrs plus a 600 mg dose of EFZ. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Retosiban | Drug | Retosiban will be supplied as clear colorless solution for infusion (300 mg in 20 mL via). Subject will receive loading dose of 6 mg over 5 min infusion followed by 6 mg/hour infusion for 12 hrs on Day 1 and Day 18. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma GSK221149 (parent) and GSK2847065 (metabolite) PK parameters of AUC, Cmax and CL. | The following PK parameters will be determined after administration of GSK221149 with and without EFZ 600 mg: Area under the plasma concentration-time curve (AUC)- from time zero to time t [AUC(0-t)] and from time zero extrapolated to infinite time [AUC(0-infinity)], maximum observed plasma concentration (Cmax) and clearance (CL). CL will be calculated for parent only. | 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours (hrs) after the start of the infusion on Day 1 and Day 18. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of administration of GSK221149 with and without EFZ 600 mg as assessed by adverse event, concurrent medication review, clinical laboratory tests, ECG, and vital signs measurements. | Clinical laboratory tests will include hematology, clinical chemistry and urinalysis parameters. Triplicate 12-lead ECGs will be obtained at the screening visit. Single 12-lead ECGs will be obtained at other time points during the study. Vital sign measurements will include systolic and diastolic blood pressure and pulse rate. |
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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 |
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| Label | URL |
|---|---|
| Results for study 116073 can be found on the GSK Clinical Study Register. | View source |
| 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 |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116073 | Annotated Case Report Form | 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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| 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 |
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| ID | Term |
|---|---|
| C522194 | GSK221149A |
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| EFZ 600 mg | Drug | EZF 600 mg will be supplied as a yellow, capsular-shaped, film-coated tablet. Subjects will receive EFZ 600mg OD in the evening from Day 3 till Day 18. |
|
| Up to 8 Weeks |
| Plasma GSK221149 and GSK2847065 PK parameters of tmax, tlag and t1/2. | The following PK parameters will be determined after administration of GSK221149 with and without EFZ 600 mg: time to Cmax (tmax), lag time (tlag), and terminal phase half-life (t1/2). The terminal half-life (t1/2) is defined as the time required for the plasma concentration of drug to reach half of its original concentration. | 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours (hrs) after the start of the infusion on Day 1 and Day 18. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116073 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D000091642 | Urogenital Diseases |