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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01622673
First received: June 15, 2012
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Raltegravir
Drug: TUMS® Ultra Strength
Drug: MINTOX® Maximum Strength
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) [ Time Frame: 12 hours postdose ] [ Designated as safety issue: No ]
    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 Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) [ Time Frame: 12 hours postdose ] [ Designated as safety issue: No ]
    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 Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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 Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 7 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 27
Study Start Date: June 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid
Experimental: TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid
Experimental: MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid
Experimental: RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid
Experimental: TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid
Experimental: MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL
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.
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.

Other Names:
  • RAL
  • ISENTRESS™
  • MK-0518
Drug: 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.

Other Names:
  • TUMS
  • calcium carbonate antacid
Drug: 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.

Other Names:
  • MINTOX
  • magnesium/aluminum hydroxide antacid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01622673     History of Changes
Other Study ID Numbers: 0518-247
Study First Received: June 15, 2012
Results First Received: July 11, 2013
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Aluminum Hydroxide
Aluminum hydroxide, magnesium hydroxide, drug combination
Aluminum hydroxide, magnesium hydroxide, simethicone drug combination
Antacids
Anti-Ulcer Agents
Magnesium Hydroxide
TEMPO
Adjuvants, Immunologic
Antioxidants
Gastrointestinal Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014