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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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This study will be a phase 1, open label, parallel group, three period crossover study to evaluate the effect of dolutegravir (DTG) on the steady state pharmacokinetics of metformin and on the safety and tolerability of dolutegravir and metformin. 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. Eligible subjects will be assigned to one of the two treatment cohorts. Subjects will receive metformin 500 milligram (mg) after every 12 hours (q12h) for 5 days in Period 1; metformin 500 mg q12h plus dolutegravir 50 mg after every 24 hours (q24h) (Cohort 1) or 50 mg q12h (Cohort 2) for 7 days in Period 2; and metformin 500 mg q12h for 10 days in Period 3. There will be no washout periods between treatments. All doses of study drug will be taken following a meal. Safety evaluations will be collected during each period. Serial pharmacokinetic (PK) samples will be collected for metformin on the last day of each period and for dolutegravir on the last day of Period 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin immediate release (IR) 500 mg q12h following a moderate fat meal for 5 days (Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q24h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 of period 3). |
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| Cohort 2 | Experimental | All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin IR 500 mg q12h following a moderate fat meal (Day 1-5 of Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q12h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 of period 3). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin 500 mg q12h | Drug | Metformin will be supplied as 500 mg tablet to be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Steady state plasma metformin pharmacokinetics (PK) parameters | PK parameters will include: maximum concentration (Cmax), area under the time-concentration curve over the dosing interval [AUC(0-tau)] | Day 5 to Day 22 |
| Steady state plasma DTG PK parameters | PK parameters will include: Area under the time-concentration curve over the dosing interval [AUC(0-tau)], apparent clearance following oral dosing (CL/F), concentration at time zero (C0) and maximum concentration (Cmax) | Day 12 and Day 13 |
| Steady-state plasma metformin PK parameters in Period 2 as compared to those in Period 1 | PK parameters will include: Terminal phase half-life (t1/2) and Apparent clearance following oral dosing (CL/F) | Day 5 to Day 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in vital signs | Vital signs will include systolic and diastolic blood pressure and pulse rate. | Upto Day 22 |
| Number of subjects with adverse events (AEs) | AEs will be assessed throughout the study. |
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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 |
|---|---|---|---|
| 26974526 | Derived | Song IH, Zong J, Borland J, Jerva F, Wynne B, Zamek-Gliszczynski MJ, Humphreys JE, Bowers GD, Choukour M. The Effect of Dolutegravir on the Pharmacokinetics of Metformin in Healthy Subjects. J Acquir Immune Defic Syndr. 2016 Aug 1;72(4):400-7. doi: 10.1097/QAI.0000000000000983. |
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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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| ID | Term |
|---|---|
| D008687 | Metformin |
| C562325 | dolutegravir |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Dolutegravir 50 mg q24h | Drug | Dolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken once a day in the morning in Period 2 (Total daily dose 50 mg per day for Cohort 1 only) |
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| Dolutegravir 50 mg q12h | Drug | Dolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken 50 mg tablets every 12 hours in Period 2 (Total daily dose 100 mg per day for Cohort 2 only). |
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| Upto Day 22 |
| Toxicity grading of clinical laboratory tests | Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters. | Upto Day 22 |
| Steady-state plasma metformin PK parameters in Period 3 for each cohort | PK parameters will include: Cmax, concentration curve over the dosing interval [AUC(0-tau)], Terminal phase half-life (t1/2) and apparent clearance following oral dosing (CL/F) | Upto Day 22 |
| Changes in serum creatinine upon dosing and discontinuation of DTG | Serum creatinine change will be calculated from baseline over time in each period | Upto Day 22 |
| 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 |