A Study to Evaluate the Effects of Calcium Carbonate and Ferrous Fumarate on Pharmacokinetics of Dolutegravir in Healthy Adult Subjects
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    


Intervention name(s): Dolutegravir 50 mg; Calcium Carbonate 1200 mg; Ferrous Fumarate 324 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): One tablet ( 50 mg) will be administered orally as a single dose in each period per the random code; 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.; 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.
Intervention MeSH terms: Ferrous fumarate; Dolutegravir; Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dolutegravir, pharmacokinetics, calcium, iron, drug interaction, healthy volunteers