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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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This study will be a phase I, open label, three period, fixed sequence crossover study to evaluate the effect of Carbamazepine (CBZ) on the steady-state pharmacokinetics of Dolutegravir (DTG) and on the safety and tolerability of DTG. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. There is no washout between treatment periods.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DTG/CBZ | Experimental | All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive DTG 50 mg once daily (OD) for 5 days (Period 1), followed by CBZ 100 mg twice daily (BID) for 3 days (days 1-3 of Period 2), CBZ 200 mg BID for 3 days (days 4-6 of Period 2), CBZ 300mg BID for 10 days (days 7-16 of Period 2), followed by DTG 50 mg OD in combination with CBZ 300mg BID for 5 days (Period 3). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DTG | Drug | DTG will be supplied as 50 mg tablet to be administered orally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Steady state plasma DTG pharmacokinetics (PK) parameters | PK parameters will include: Steady state plasma DTG concentration at the end of the dosing interval (Ctau), maximum concentration (Cmax), area under the time-concentration curve over the dosing interval [AUC(0-tau)], apparent clearance following oral dosing (CL/F), terminal phase half life (t1/2), concentration at time zero (C0) and minimum concentration (Cmin) | Day 5 and Day 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in 12-lead electrocardiogram (ECG) | Single 12-lead ECGs will be obtained at each timepoint | Up to 40 days |
| Change from baseline in vital signs | Vital signs 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 | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26898568 | Derived | Song I, Weller S, Patel J, Borland J, Wynne B, Choukour M, Jerva F, Piscitelli S. Effect of carbamazepine on dolutegravir pharmacokinetics and dosing recommendation. Eur J Clin Pharmacol. 2016 Jun;72(6):665-70. doi: 10.1007/s00228-016-2020-6. Epub 2016 Feb 22. |
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| ID | Term |
|---|---|
| D007239 | Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
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| CBZ |
| Drug |
CBZ will be supplied as 100 mg and 200 mg extended release tablet to be administered orally |
|
| Up to 40 days |
| Number of subjects with adverse events (AEs) | AEs will be assessed throughout the study | Up to 40 days |
| Toxicity grading of clinical laboratory tests | Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters | Up to 40 days |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |