A Phase 1 interventional study of Metformin 500 mg q12h and Dolutegravir 50 mg q24h in Infection, Human Immunodeficiency Virus, sponsored by ViiV Healthcare. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-05-26.
Sponsored by ViiV Healthcare · Phase 1, Interventional, and Treatment
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.
2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.
This study's enrollment of 30 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.
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Exclusion Criteria:
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).
Drug: Metformin 500 mg q12h · Drug: Dolutegravir 50 mg q24h
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).
Drug: Metformin 500 mg q12h · Drug: Dolutegravir 50 mg q12h
Metformin will be supplied as 500 mg tablet to be administered orally.
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)
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).
Steady state plasma metformin pharmacokinetics (PK) parameters
PK parameters will include: maximum concentration (Cmax), area under the time-concentration curve over the dosing interval \[AUC(0-tau)\]
Time frame: 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)
Time frame: 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)
Time frame: Day 5 to Day 12
Change from baseline in vital signs
Vital signs will include systolic and diastolic blood pressure and pulse rate.
Time frame: Upto Day 22
Number of subjects with adverse events (AEs)
AEs will be assessed throughout the study.
Time frame: Upto Day 22
Toxicity grading of clinical laboratory tests
Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters.
Time frame: 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)
Time frame: 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
Time frame: Upto Day 22
This study is completed, as verified in May 2014. You cannot join it, but the record below documents what was studied.
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Acquired Immunodeficiency Syndrome→
ViiV Healthcare