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A Pharmacokinetic Study to Evaluate the Effect of MAALOX on Raltegravir (MK-0518) in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-295)

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Raltegravir (ISENTRESS™)
MAALOX (MAL)
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:

  • On a stable raltegravir dose as part of a stable antiretroviral regimen for ≥1 month before the study
  • If female, is not pregnant or breast feeding
  • Body mass index ≤32 kg/m^2

Exclusion Criteria:

  • Mentally or physically incapacitated, has significant emotional problems, or history of clinically significant psychiatric disorder within ≤10 years
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease (excluding HIV)
  • History of gastric bypass surgery
  • History of cancer, except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years before the study
  • History of chronic diarrhea within ≤3 months before the study
  • History of significant multiple and/or severe allergies (food, drug, latex), or had an anaphylactic reaction or significant intolerability to drugs or food
  • Had major surgery or donated or lost ≥1 unit of blood (500 mL) ≤4 weeks before the study
  • Participated in another investigational trial ≤4 weeks before the study
  • Taking rifampin or is unable to refrain from the use of 1) any proton pump inhibitor from 2 weeks before and throughout the study, or 2) any histamine H2-blockers, antacids, calcium supplements, or multivitamins from 2 weeks before and throughout the study
  • Consumes >3 glasses of alcoholic beverages per day
  • Consumes excessive amounts of caffeine beverages (coffee, tea, cola, energy drinks, or other caffeinated drinks) per day
  • Currently uses or has a history of drug abuse within ≤6 months before the study

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

    Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL

    MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL

    Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL

    Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt

    MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt

    Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt

    Arm Description

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Raltegravir (Ralt) alone in Period 1, MAALOX (MAL) followed 4 hrs later by Ralt in Period 2, Ralt followed 4 hrs later by MAL in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt followed 4 hrs later by MAL in Period 2, Ralt alone in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, Ralt alone in Period 2, MAL followed 4 hrs later by Ralt in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt alone in Period 1, Ralt followed 4 hrs later by MAL in Period 2, MAL followed 4 hrs later by Ralt in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt alone in Period 2, Ralt followed 4 hrs later by MAL in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5

    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, MAL followed 4 hrs later by Ralt in Period 2, Ralt alone in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5

    Outcomes

    Primary Outcome Measures

    Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1
    Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
    Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 1
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir in order to determine the geometric mean area under the curve plasma concentration versus time.
    Maximum Plasma Concentration (C Max) of Raltegravir in Part 1
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.
    Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 2
    Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
    Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 2
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean area under the curve plasma concentration versus time.
    Maximum Plasma Concentration (C Max) of Raltegravir in Part 2
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.

    Secondary Outcome Measures

    Full Information

    First Posted
    August 23, 2013
    Last Updated
    July 25, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01930045
    Brief Title
    A Pharmacokinetic Study to Evaluate the Effect of MAALOX on Raltegravir (MK-0518) in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-295)
    Official Title
    A Study to Evaluate the Effect of Staggered Dosing of a Magnesium/Aluminum Antacid on Raltegravir Pharmacokinetics in HIV-Infected Subjects on a Raltegravir-Containing Regimen
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 1, 2013 (Actual)
    Primary Completion Date
    December 10, 2013 (Actual)
    Study Completion Date
    December 10, 2013 (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 evaluated the effect of single doses of a magnesium/aluminum antacid (MAALOX) given 4 and 6 hours before or after administration of raltegravir, on the pharmacokinetics of raltegravir in human immunodeficiency virus (HIV)-infected participants. The study consisted of Part 1 (Periods 1, 2, and 3) and Part 2 (Periods 4 and 5), with each study period separated by a washout period of at least 2 days; Part 1 was separated from Part 2 by a Pause. Each study period had a duration of ≥2 days, and paused for evaluation of Part 1 pharmacokinetics results before continuing to Part 2. The same participants participated in Parts 1 and 2. The primary hypothesis tested (in Part 1) was that raltegravir plasma concentration 12 hours after administration (C 12 hrs) would not differ significantly from raltegravir C 12 hrs when antacid is administered 4 hours before or 4 hours after raltegravir.

    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
    18 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Raltegravir (Ralt) alone in Period 1, MAALOX (MAL) followed 4 hrs later by Ralt in Period 2, Ralt followed 4 hrs later by MAL in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5
    Arm Title
    MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt followed 4 hrs later by MAL in Period 2, Ralt alone in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5
    Arm Title
    Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, Ralt alone in Period 2, MAL followed 4 hrs later by Ralt in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5
    Arm Title
    Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt alone in Period 1, Ralt followed 4 hrs later by MAL in Period 2, MAL followed 4 hrs later by Ralt in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5
    Arm Title
    MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt alone in Period 2, Ralt followed 4 hrs later by MAL in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5
    Arm Title
    Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt
    Arm Type
    Experimental
    Arm Description
    Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, MAL followed 4 hrs later by Ralt in Period 2, Ralt alone in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5
    Intervention Type
    Drug
    Intervention Name(s)
    Raltegravir (ISENTRESS™)
    Intervention Description
    Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
    Intervention Type
    Drug
    Intervention Name(s)
    MAALOX (MAL)
    Other Intervention Name(s)
    MAALOX® MS
    Intervention Description
    MAL (or generic equivalent) 20 mL oral single dose on Day 1
    Primary Outcome Measure Information:
    Title
    Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1
    Description
    Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
    Time Frame
    12 hours after dosing on Day 1 of each period
    Title
    Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 1
    Description
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir in order to determine the geometric mean area under the curve plasma concentration versus time.
    Time Frame
    Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period
    Title
    Maximum Plasma Concentration (C Max) of Raltegravir in Part 1
    Description
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.
    Time Frame
    Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period
    Title
    Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 2
    Description
    Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
    Time Frame
    12 hours after dosing on Day 1 of each period
    Title
    Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 2
    Description
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean area under the curve plasma concentration versus time.
    Time Frame
    Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period
    Title
    Maximum Plasma Concentration (C Max) of Raltegravir in Part 2
    Description
    Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.
    Time Frame
    Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: On a stable raltegravir dose as part of a stable antiretroviral regimen for ≥1 month before the study If female, is not pregnant or breast feeding Body mass index ≤32 kg/m^2 Exclusion Criteria: Mentally or physically incapacitated, has significant emotional problems, or history of clinically significant psychiatric disorder within ≤10 years History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease (excluding HIV) History of gastric bypass surgery History of cancer, except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years before the study History of chronic diarrhea within ≤3 months before the study History of significant multiple and/or severe allergies (food, drug, latex), or had an anaphylactic reaction or significant intolerability to drugs or food Had major surgery or donated or lost ≥1 unit of blood (500 mL) ≤4 weeks before the study Participated in another investigational trial ≤4 weeks before the study Taking rifampin or is unable to refrain from the use of 1) any proton pump inhibitor from 2 weeks before and throughout the study, or 2) any histamine H2-blockers, antacids, calcium supplements, or multivitamins from 2 weeks before and throughout the study Consumes >3 glasses of alcoholic beverages per day Consumes excessive amounts of caffeine beverages (coffee, tea, cola, energy drinks, or other caffeinated drinks) per day Currently uses or has a history of drug abuse within ≤6 months before the study
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=0518-295&kw=0518-295&tab=access

    Learn more about this trial

    A Pharmacokinetic Study to Evaluate the Effect of MAALOX on Raltegravir (MK-0518) in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-295)

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