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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01930045
First received: August 23, 2013
Last updated: October 29, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Raltegravir (ISENTRESS™)
Drug: MAALOX (MAL)
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 Staggered Dosing of a Magnesium/Aluminum Antacid on Raltegravir Pharmacokinetics in HIV-Infected Subjects on a Raltegravir-Containing Regimen

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1 [ Time Frame: 12 hours after dosing on Day 1 of each period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 hours after dosing on Day 1 of each period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period ] [ Designated as safety issue: No ]
    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.


Enrollment: 18
Study Start Date: October 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS
Experimental: MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS
Experimental: Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS
Experimental: Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS
Experimental: MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS
Experimental: Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt
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
Drug: Raltegravir (ISENTRESS™)
Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.
Drug: MAALOX (MAL)
MAL (or generic equivalent) 20 mL oral single dose on Day 1
Other Name: MAALOX® MS

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01930045

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01930045     History of Changes
Other Study ID Numbers: 0518-295
Study First Received: August 23, 2013
Results First Received: October 29, 2014
Last Updated: October 29, 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
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Aluminum hydroxide, magnesium hydroxide, drug combination
Antacids
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 24, 2014