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

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: Raltegravir (ISENTRESS™); Drug: MAALOX (MAL)

• Registration Number: NCT01930045
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-23
• Study First Submitted QC: 2013-08-23
• Study First Posted: 2013-08-28
• Study Start: 2013-10-01
• Primary Completion: 2013-12-10
• Study Completion: 2013-12-10
• Results First Submitted: 2014-10-29
• Results First Submitted QC: 2014-10-29
• Results First Posted: 2014-11-02
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-25
• Last Update Posted: 2018-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL	Raltegravir (ISENTRESS™)	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
Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt	Raltegravir (ISENTRESS™)	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
MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt	Raltegravir (ISENTRESS™)	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
Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL	MAALOX (MAL)	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
Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL	Raltegravir (ISENTRESS™)	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
MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL	MAALOX (MAL)	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
Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL	MAALOX (MAL)	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
Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL	Raltegravir (ISENTRESS™)	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
Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt	MAALOX (MAL)	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
MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt	MAALOX (MAL)	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
Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt	Raltegravir (ISENTRESS™)	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
Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt	MAALOX (MAL)	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

Primary Outcome Measures

Name	Time	Method
Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1	12 hours after dosing on Day 1 of each period	Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
Maximum Plasma Concentration (C Max) of Raltegravir in Part 1	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period	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.
Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 2	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period	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	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period	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.
Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 1	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period	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.
Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 2	12 hours after dosing on Day 1 of each period	Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.