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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Drug: TUMS® Ultra Strength; Drug: Raltegravir; Drug: MINTOX® Maximum Strength

Study type: Interventional

Funder types: Industry

Identifiers

NCT01622673

0518-247

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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27 participants in 6 patient groups

RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength

TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength

MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength

RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength

TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength

MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL

Experimental group

Description:

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.

Treatment:

Drug: MINTOX® Maximum Strength

Drug: Raltegravir

Drug: TUMS® Ultra Strength