Clinical trial NCT01622673: A Pharmacokinetic Study to Evaluate the Effect of Antacids on Raltegravir (MK-0518) in HIV-Infected Participants (MK-0518-247)
Official title: A Study to Evaluate the Effect of Metal Cation-Containing Antacids on Raltegravir Pharmacokinetics in HIV-Infected Subjects on a Stable Raltegravir-Containing Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-06-19
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will evaluate: (1) the effect of co-administration of single doses of calcium carbonate antacid and magnesium/aluminum hydroxide antacid on the steady-state plasma pharmacokinetic profile of raltegravir in human immunodeficiency virus (HIV)-infected participants; and (2) the effect of staggered dosing of a single dose of a magnesium/aluminum hydroxide antacid 2 hours before and 2 hours after administration of raltegravir on the steady-state plasma pharmacokinetic profile of raltegravir in the same participants.

The study will determine whether (1) the C12hrs of steady-state raltegravir after co-administration of single doses of calcium carbonate antacid is decreased to a clinically meaningful degree compared with C12hrs after administration of raltegravir alone; and whether (2) the C12hrs of steady-state raltegravir after co-administration of a single dose of magnesium/aluminum hydroxide antacid is decreased to a clinically meaningful degree compared with the C12hrs after administration of raltegravir alone.


Eligibility criteria: Inclusion Criteria:

* HIV-infected participant on a stable raltegravir dose (400 mg every 12 hours) as part of a stable anti-retroviral regimen (ARV) for at least 1 month and will maintain current ARV therapy throughout the study
* Body Mass Index ≤32 kg/m\^2
* Good general health
* Can be a current smoker and/or user of nicotine or nicotine-containing products, but use of nicotine-containing products will not be permitted during the stay at the clinical research site

Exclusion Criteria:

* History of gastric bypass surgery
* Pregnant or nursing
* Mentally or legally incapacitated, has significant emotional problems, or has a history of a clinically significant psychiatric disorder; participants who have had situational depression may be enrolled at the discretion of the investigator.
* History of stroke, chronic seizures, or major neurological disorder
* History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases (excluding HIV); participants with a history of uncomplicated kidney stones or childhood asthma may be enrolled at the discretion of the investigator.
* Active neoplastic disease deemed unstable or progressing by the investigator
* Currently taking rifampin or unable to refrain from use of any proton pump inhibitor and any histamine-2 (H2)-blockers, over-the-counter antacids, calcium supplements, or multivitamins during the study
* Consumes excessive amounts of alcohol
* Consumes excessive amounts of coffee, tea, cola, or other caffeinated beverages
* Major surgery or blood donation within the past 4 weeks
* History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Regular user of any illicit drugs or history of drug (including alcohol) abuse within the past 6 months; current methadone or suboxone use is allowed.

Primary outcomes:
measure: Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
timeFrame: 12 hours postdose
measure: Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
timeFrame: 12 hours postdose
measure: Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
measure: Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
measure: Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
measure: Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
measure: Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
measure: Number of Participants With Any Clinical or Laboratory Adverse Event (AE)
timeFrame: Up to 7 days after the last dose of study drug
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Kiser JJ, Bumpass JB, Meditz AL, Anderson PL, Bushman L, Ray M, Predhomme JA, Rower J, Mawhinney S, Brundage R. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Antimicrob Agents Chemother. 2010 Dec;54(12):4999-5003. doi: 10.1128/AAC.00636-10. Epub 2010 Oct 4.