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

NCT ID: NCT01622673

Last Updated: 2017-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2012-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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.

TUMS® Ultra Strength

Intervention Type: 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.

MINTOX® Maximum Strength

Intervention Type: 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.

Interventions

Raltegravir

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.

Intervention Type: DRUG

TUMS® Ultra Strength

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.

Intervention Type: DRUG

MINTOX® Maximum Strength

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.

Intervention Type: DRUG

Other Intervention Names

RAL; ISENTRESS™; MK-0518; TUMS; calcium carbonate antacid; MINTOX; magnesium/aluminum hydroxide antacid

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: RESULT

PMID: 20921313 (View on PubMed)

Other Identifiers

0518-247

Identifier Type: -

Identifier Source: org_study_id