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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Raltegravir
TUMS® Ultra Strength
MINTOX® Maximum Strength
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

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

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

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

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

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

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

    Arm 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.

    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.

    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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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®.
    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®.
    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®.
    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®.
    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®.
    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®.
    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
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    June 15, 2012
    Last Updated
    February 14, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01622673
    Brief Title
    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

    2. Study Status

    Record Verification Date
    February 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2012 (undefined)
    Primary Completion Date
    October 2012 (Actual)
    Study Completion Date
    October 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    27 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Raltegravir
    Other Intervention Name(s)
    RAL, ISENTRESS™, MK-0518
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    TUMS® Ultra Strength
    Other Intervention Name(s)
    TUMS, calcium carbonate antacid
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    MINTOX® Maximum Strength
    Other Intervention Name(s)
    MINTOX, magnesium/aluminum hydroxide antacid
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
    Description
    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®.
    Time Frame
    12 hours postdose
    Title
    Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
    Description
    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®.
    Time Frame
    12 hours postdose
    Title
    Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
    Description
    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®.
    Time Frame
    Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
    Title
    Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
    Description
    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®.
    Time Frame
    Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
    Title
    Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
    Description
    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®.
    Time Frame
    Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
    Title
    Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
    Description
    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®.
    Time Frame
    Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
    Title
    Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir
    Description
    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
    Time Frame
    Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
    Title
    Number of Participants With Any Clinical or Laboratory Adverse Event (AE)
    Description
    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.
    Time Frame
    Up to 7 days after the last dose of study drug

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    20921313
    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.
    Results Reference
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    A Pharmacokinetic Study to Evaluate the Effect of Antacids on Raltegravir (MK-0518) in HIV-Infected Participants (MK-0518-247)

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