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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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Human immune virus (HIV) infected subjects may take mineral supplements in combination with their antiretroviral medications. Calcium and Iron supplementations are commonly used and both of these have the potential to interact with Dolutegravir (DTG), this study will evaluate the potential of calcium and iron supplements to decrease DTG exposure. It will also evaluate two possible strategies for combined use; if an interaction is observed. The first strategy is a two hour separation. The second strategy involves the administration of DTG and the supplement with a meal since the presence of food modestly increases DTG exposure, and because mineral supplements can be administered with food.
This is an open label, randomized, two cohort, four-period cross-over study in healthy volunteers. One cohort will examine the effects of calcium carbonate and the other cohort will examine the effects of ferrous fumarate on the pharmacokinetic (PK) of DTG. Approximately 12 subjects will be enrolled into each of the two cohorts and receive each of four treatments in a randomized fashion: 1) A single dose of DTG 50 milligram (mg) administered under fasted conditions ; 2) A single dose of DTG 50 mg co-administered with a single dose of calcium carbonate or ferrous fumarate under fasted conditions ; 3) A single dose of DTG 50 mg co-administered with a single dose of calcium carbonate or ferrous fumarate with a moderate-fat meal; 4) A single dose of DTG 50 mg administered under fasted conditions 2 hours prior to administration of a single dose of calcium carbonate or ferrous fumarate. There will be a washout period of at least 7 days between treatments. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. This study will be conducted at one center in the United States, with healthy adult male and female subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Subjects in this cohort will take part in 4 treatment periods with one of the following treatments in each period. Subjects will receive all four treatments (one per period) in a random order. Treatment A = single dose DTG 50 mg fasted. Treatment B = single dose DTG 50 mg + Calcium Carbonate 1200 mg fasted. Treatment C = single dose of DTG 50 mg + Calcium Carbonate 1200 mg fed. Treatment D = single dose DTG 50 mg 2 hours prior to single dose Calcium Carbonate 1200 mg fasted |
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| Cohort 2 | Experimental | Subjects in this cohort will take part in 4 treatment periods with one of the following treatments in each period. Subjects will receive all four treatments (one per period) in a random order. Treatment A = single dose DTG 50 mg fasted. Treatment E = single dose DTG 50 mg + Ferrous Fumarate 324 mg fasted. Treatment F = single dose of DTG 50 mg + Ferrous Fumarate 324 mg fed. Treatment G = single dose DTG 50 mg 2 hours prior to single dose Ferrous Fumarate 324 mg fasted |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dolutegravir 50 mg | Drug | One tablet ( 50 mg) will be administered orally as a single dose in each period per the random code |
|
| Measure | Description | Time Frame |
|---|---|---|
| Single dose plasma DTG PK assessed by AUC (0-t) and AUC (0-infinity) | To evaluate the single dose PK of DTG, area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC [0-t]) and area under the concentration-time curve from time zero extrapolated to infinite time (AUC (0-infinity) will be assessed with DTG given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hours (hrs) separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted) | Blood samples (2 mililiter [mL]) for plasma PK parameters will be collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose), Day 2 (24 and 36 hrs post-dose) and Day 3 (48 hrs post- dose) in each of the four treatment periods |
| Single dose plasma DTG PK assessed by Cmax and C24 | To evaluate the single dose PK of DTG, maximum observed concentration (Cmax) and concentration at 24 hours post-dose (C24) will be assessed with DTG given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hrs separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted) | Blood samples (2 mL) for plasma PK parameters will be collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose), day 2 (24 and 36 hrs post-dose) and day 3 (48 hrs post dose) in each of the four |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability assessed by change from baseline in electrocardiogram (ECG) | Single 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. | Baseline and up to 36 days |
| Safety and tolerability assessed by number of subjects with adverse events (AEs) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
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| Calcium Carbonate 1200 mg | Drug | Two tablets (2 X 600 mg) will be administered orally as a single dose in three out of four periods to Cohort 1 only per the random code. Calcium carbonate will be given in fasted state, fed state and 2 hours before dolutegravir administration. |
|
| Ferrous Fumarate 324 mg | Drug | One tablet (324 mg) will be administered orally as a single dose in three out of four periods to Cohort 2 only per the random code. Ferrous fumarate will be given in fasted state, fed state and 2 hours before dolutegravir administration. |
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AEs will be collected from the start of Study Treatment and until the follow-up contact |
| up to 36 days |
| Safety and tolerability assessed by toxicity grading of clinical laboratory tests | Clinical laboratory tests include hematology, clinical chemistry, pregnancy test, alcohol and drug of abuse screen, and other additional parameters | up to 36 days |
| Single dose plasma DTG PK assessed by AUC (0-24) | To evaluate the single dose PK of DTG, area under the concentration-time curve from time zero to 24 hrs post dose (AUC [0-24]) will be assessed when DTG will be given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hrs separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted) | Blood samples (2 mL) for plasma PK parameter will be collected on day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose), Day 2 (24 and 36 hrs post-dose) and Day 3 (48 hrs post- dose) in each of the four treatment periods. |
| Single dose plasma DTG PK assessed by tlag, tmax, and t1/2 | To evaluate the single dose PK of DTG, lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), and terminal phase half-life (t1/2) will be assessed when DTG will be given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hrs separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted). | Blood samples (2 mL) for plasma PK parameter will be collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose), Day 2 (24 and 36 hrs post-dose) and Day 3 (48 hrs post- dose) in each of the four treatment periods. |
| Single dose plasma DTG PK assessed by CL/F | To evaluate the single dose PK of DTG, apparent clearance following oral dosing (CL/F) will be assessed when DTG will be given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hrs separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted). | Blood samples (2 mL) for plasma PK parameter will be collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose), Day 2 (24 and 36 hrs post-dose) and Day 3 (48 hrs post- dose) in each of the four treatment periods. |
| Safety and tolerability assessed by change from baseline in blood pressure | Blood pressure (BP) measurement will include systolic and diastolic BP measurement. BP will be measured after resting in a semi-supine position for 5 minutes | Baseline and up to 36 days |
| Safety and tolerability assessed by change from baseline in Pulse rate | Pulse rate will be measured after resting in a semi-supine position for 5 minutes | Baseline and up to 36 days |
| 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 |
| 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 |
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| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D002119 | Calcium Carbonate |
| C031621 | ferrous fumarate |
| ID | Term |
|---|---|
| D017610 | Calcium Compounds |
| D007287 | Inorganic Chemicals |
| D002254 | Carbonates |
| D002255 | Carbonic Acid |
| D017554 | Carbon Compounds, Inorganic |
| D008903 | Minerals |
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