The Effect of Antacids and Multivitamins on Raltegravir

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Dietary supplement: Sodium bicarbonate; Drug: Maalox Plus extra; Drug: Raltegravir 400 mg; Dietary supplement: Multivitamins

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Helen Reynolds
• Investigators: Principal Investigator: Saye Khoo, Prof, University of Liverpool

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 28, 2013
• First Submitted That Met QC Criteria: February 1, 2013
• First Posted (Estimate): February 5, 2013

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 4347