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

NCT01622673 | Completed Phase 1 Results

• 1 other identifier: 0518-247
• Study Type: interventional
• Target: 27
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (8)

• 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®.

  12 hours postdose

• 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®.

  12 hours postdose

• 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®.

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

• 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®.

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

• 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®.

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

• 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®.

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

• 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

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

• 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.

  Up to 7 days after the last dose of study drug

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

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

EXPERIMENTAL

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.

Drug: Raltegravir; Drug: TUMS® Ultra Strength; Drug: MINTOX® Maximum Strength

Interventions

Raltegravir DRUG

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.

Also known as: RAL, ISENTRESS™, MK-0518

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

TUMS® Ultra Strength DRUG

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.

Also known as: TUMS, calcium carbonate antacid

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

MINTOX® Maximum Strength DRUG

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.

Also known as: MINTOX, magnesium/aluminum hydroxide antacid

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 20921313 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; aluminum hydroxide, magnesium hydroxide, simethicone drug combination; Magnesium; Aluminum Hydroxide

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; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals; Hydroxides; Alkalies; Aluminum Compounds; Anions; Ions; Electrolytes

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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: June 15, 2012
• First Posted: June 19, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 21, 2017
• Results First Posted: September 17, 2013

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share