The Effect of Antacids and Multivitamins on Raltegravir

Study Overview
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Brief Summary
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This study seeks to address the question of whether antacids or multivitamins influence the pharmacokinetics of raltegravir when co-administered. The aim of this study is to optimise the dosing of raltegravir when co-administered with antacids or multivitamins.

Official Title
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A 3 Arm, 5 Phase Study to Determine the Effect of Divalent and Monovalent Metal Containing Antacids and Multivitamins on the Pharmacokinetics of Raltegravir in Healthy Volunteers

Conditions
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HIV

Intervention / Treatment
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* Dietary Supplement: Multivitamins
* Dietary Supplement: Sodium bicarbonate
* Drug: Maalox Plus extra
* Drug: Raltegravir 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements. ≥ 18 years Male or female subjects A female may be eligible to enter and participate in the study if she: Is of non-child-bearing potential defined as ether post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age)or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or Is of child-bearing potential with a negative pregnancy test at screening and agrees to use one of the following methods of contraception to avoid pregnancy Complete abstinence from intercourse from 2 weeks prior to administration of IP, throughout the study and for at least 4 weeks after discontinuation of all study medication Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide) Any intrauterine device (IUD) with published data showing that the expected failure rate is < 1 % per year Any other method with published data showing that the expected failure rate is < 1 % per year Hormonal contraception plus a barrier method. Hormonal contraception alone will not be considered adequate for inclusion into or participation in this study Male subjects with a female partner of childbearing potential must agree to use effective contraception as above unless vasectomized All subjects participating in the study will be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom) Exclusion Criteria: Any significant acute or chronic medical condition Pregnant or lactating women Women of childbearing age unless using non hormonal contraception Evidence of organ dysfunction or any clinically significant deviation from normal during screening including laboratory determinations Abnormal LFTs (ALT > 2.5 x ULN, bilirubin > 1.5 x ULN) Positive blood screen for HIV-1 and 2 antibodies Positive blood screen for hepatitis B or C antibodies Current or recent (within 3 months) gastrointestinal disease Clinically relevant alcohol or drug use or history of alcohol or drug use that will hinder compliance with treatment, follow up procedures or evaluation of adverse effects Use of proton pump inhibitors Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug Consumption of grapefruit and oranges or products containing grapefruit or oranges within 1 week of first study drug and for the duration of the study Use of any other drugs including over-the-counter medications and herbal preparations, within 2 weeks prior to first dose of study drug Previous allergy to any of the constituents of the pharmaceuticals in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maalox Plus extra<br>Subjects will receive doses of raltegravir 400 mg and maalox plus extra | Drug: Maalox Plus extra<br> <br> Drug: Raltegravir 400 mg<br> <br> |
| Active Comparator: Multivitamin<br>Subjects will receive doses of raltegravir 400 mg along with a multivitamin tablet | Dietary Supplement: Multivitamins<br> <br> Drug: Raltegravir 400 mg<br> <br> |
| Active Comparator: Sodium bicarbonate<br>Subjects will receive doses of raltegravir 400 mg along with sodium bicarbonate | Dietary Supplement: Sodium bicarbonate<br> <br> Drug: Raltegravir 400 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in raltegravir Area under the curve (AUC)0-12h | The primary endpoint will be a change in raltegravir AUC0-12 h, following dosing of antacid or multivitamin | Day 1, 6, 11, 16 and 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of gastrointestinal pH | Correlation between gastric pH and raltegravir pharmacokinetics | Day 1, 6, 11, 16 and 21 | 
| Number of adverse events |  | Day 1 up to end of study Day 27 |