A Pharmacokinetic Study to Evaluate the Effect of Antacids on Raltegravir (MK-0518) in HIV-Infected Participants (MK-0518-247)

Phase 1

Completed

Conditions: HIV Infections

Interventions: Drug: Raltegravir
Drug: TUMS® Ultra Strength
Drug: MINTOX® Maximum Strength

Registration Number: NCT01622673

Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL	TUMS® Ultra Strength	Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL	TUMS® Ultra Strength	Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours After Raltegravir in treatment period 5. There was a 2-day washout between treatment periods.
RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL	MINTOX® Maximum Strength	Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours After Raltegravir in treatment period 5. There was a 2-day washout between treatment periods.
TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL	Raltegravir	Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL	TUMS® Ultra Strength	Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL	MINTOX® Maximum Strength	Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL	TUMS® Ultra Strength	Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL	MINTOX® Maximum Strength	Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL	MINTOX® Maximum Strength	Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL	TUMS® Ultra Strength	Participants received TUMS® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL	MINTOX® Maximum Strength	Participants received TUMS® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL	TUMS® Ultra Strength	Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL	MINTOX® Maximum Strength	Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL	Raltegravir	Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours After Raltegravir in treatment period 5. There was a 2-day washout between treatment periods.
MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL	Raltegravir	Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL	Raltegravir	Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL	Raltegravir	Participants received TUMS® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL	Raltegravir	Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.

Primary Outcome Measures

Name	Time	Method
Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	12 hours postdose	Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	Participant blood samples were collected to measure the steady state maximum plasma concentration of raltegravir when administered alone or with a single dose of antacid. The primary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when coadministered with TUMS® or MINTOX®.
Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	12 hours postdose	Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	Participant blood samples were collected to measure the maximum steady state plasma concentration of raltegravir after administration alone or before or after a single dose of antiacid. The secondary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when administered 2 hours before or after MINTOX®.
Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	Participant blood samples were collected to measure the time to achieve the maximum steady state plasma concentration of raltegravir when administered alone or with a single dose of antacid
Number of Participants With Any Clinical or Laboratory Adverse Event (AE)	Up to 7 days after the last dose of study drug	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.