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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01622673
• Other study ID #: 0518-247
• Status: Completed
• Phase: Phase 1
• First received: June 15, 2012
• Last updated: February 6, 2015
• Start date: June 2012
• Est. completion date: October 2012

Study information

• Verified date: February 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Raltegravir
Raltegravir 400 mg oral tablet taken with 240 mL water every 12 hours Throughout the study, participants will continue to take raltegravir along with their other HIV medications. On the day of co-dosing and intensive pharmacokinetic (PK) sampling, raltegravir will be dosed in the morning in a fasted state in all periods.
• TUMS® Ultra Strength
3 tablets TUMS® Ultra Strength (US) 1000 mg Throughout the study, participants will continue to take raltegravir every 12 hours along with their other HIV medications. There will be a minimum of 2 days washout between treatment periods. On the day of co-dosing and intensive PK sampling, raltegravir will be dosed in the morning in a fasted state in all periods.
• MINTOX® Maximum Strength
20 mL MINTOX® Maximum Strength (MS) Throughout the study, participants will continue to take raltegravir every 12 hours along with their other HIV medications. There will be a minimum of 2 days washout between treatment periods. On the day of co-dosing and intensive PK sampling, raltegravir will be dosed in the morning in a fasted state in all periods.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	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®.	12 hours postdose	No
Primary	Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	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®.	12 hours postdose	No
Primary	Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	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®.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	No
Primary	Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	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®.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	No
Primary	Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)	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®.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	No
Primary	Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)	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®.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	No
Primary	Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir	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	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose	No
Primary	Number of Participants With Any Clinical or Laboratory Adverse Event (AE)	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.	Up to 7 days after the last dose of study drug	Yes