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

NCT01930045 | Completed Phase 1 Results

• 1 other identifier: 0518-295
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (6)

• 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.

  12 hours after dosing on Day 1 of each period

• 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.

  Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period

• 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.

  Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period

• 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.

  12 hours after dosing on Day 1 of each period

• 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.

  Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period

• 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.

  Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period

Study Arms (6)

Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt

EXPERIMENTAL

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™); Drug: MAALOX (MAL)

Interventions

Raltegravir (ISENTRESS™) DRUG

Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study.

MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL; MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt; Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt; Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL; Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL; Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt

MAALOX (MAL) DRUG

MAL (or generic equivalent) 20 mL oral single dose on Day 1

Also known as: MAALOX® MS

MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL; MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt; Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt; Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL; Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL; Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; aluminum hydroxide, magnesium hydroxide, drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: August 28, 2013
• Study Start: October 1, 2013
• Primary Completion: December 10, 2013
• Study Completion: December 10, 2013
• Last Updated: August 24, 2018
• Results First Posted: November 3, 2014

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share