The Effect of Antacids on the Pharmacokinetics (PK) of Raltegravir in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-824)

Study Overview
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Brief Summary
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In order to define the safe windows for co-dosing of metal-cation antacids with once daily administered raltegravir, this study will evaluate the effect of both calcium carbonate and magnesium/aluminum hydroxide antacids on the pharmacokinetics of raltegravir, due to dosage of 1200 mg raltegravir in HIV-infected participants already taking 400 mg raltegravir twice daily as part of their HIV treatment regimen.

Official Title
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A Study to Evaluate the Influence of Metal Cation-Containing Antacids on MK-0518 Pharmacokinetics in HIV-Infected Subjects on a Stable Raltegravir-Containing Regimen

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Raltegravir 1200 mg
* Drug: TUMS
* Drug: Leader Antacid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is HIV positive Is on a stable raltegravir-containing (400 mg every 12hr) antiretroviral (ARV) regimen for at least 1 month prior to study entry, with no changes, including dose adjustments; and agrees to maintain their current ARV therapy throughout the study. Be male, or a non-pregnant and non-breast feeding female at least 18 years of age at the pre-trial (screening) Has a Body Mass Index (BMI) =< 32 kg/m^2 Exclusion Criteria: Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases (excluding HIV) Has a history of gastric bypass surgery Has a history of cancer (malignancy) Has a history of chronic diarrhea within approximately 3 months prior to the pre-trial visit Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-trial visit Has participated in another investigational trial within 4 weeks prior to the pre-trial visit Is currently taking rifampin or atazanavir or is unable to refrain from the use of 1) any proton pump inhibitor from two weeks prior to the study through the completion of Period 4, and 2) any H2-blockers, over-the-counter antacids, calcium supplements or multivitamins from one week prior to the study through the completion of Period 4 Consumes greater than 3 glasses of alcoholic beverages or distilled spirits per day Consumes greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day Is currently a regular user (including recreational use) of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raltegravir Pre- and 4 Period Sequence<br>Starting five days prior to Period 1 participants will be treated with 1200 mg raltegravir, once daily for five days. In Period 1 participants will be treated with 1200 raltegravir alone; this is followed by Period 2 where participants will be treated with 1200 mg raltegravir and TUMS concomitantly; this is followed by Period 3 where participants will be treated with 1200 mg raltegravir and 12 hours later with Leader Antacid; followed by Period 4 where participants will be treated with 1200 mg raltegravir and 12 hours later with TUMS. The wait between Periods is 2-7 days. | Drug: Raltegravir 1200 mg<br>* Two tablets of 600 mg raltegravir administered orally, once daily, over 5 days of Pre-treatment, and once at the start of Periods 1-4.<br>Drug: TUMS<br>* Three tablets of TUMS Ultra Strength (US) 1000, taken orally, concomitantly with raltegravir in Period 2, and 12 hours after raltegravir in Period 4<br>Drug: Leader Antacid<br>* 20 mL Leader Antacid Maximum Strength (MS) taken orally 12 hours after raltegravir, in Period 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir | In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS Ultra Strength (US) 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid Maximum Strength (MS) taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and analysis of variance (ANOVA) modeling was performed on natural log-transformed values to derive geometric least-squares means. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | 
| Maximum Plasma Concentration (Cmax) of Raltegravir Following Once Daily Administration of Raltegravir | In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | 
| Plasma Concentration at 24 Hrs Post-dose (C24hr) of Raltegravir Following Once Daily Administration of Raltegravir | In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected at 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means. | 24 hours post-dose |