The Effect of Antacids on the Pharmacokinetics (PK) of Raltegravir in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-824)

NCT ID: NCT02473367

Last Updated: 2018-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-23
• Study Completion Date: 2015-10-09

Brief Summary

In order to define the safe windows for co-dosing of metal-cation antacids with once daily administered raltegravir, this study will evaluate the effect of both calcium carbonate and magnesium/aluminum hydroxide antacids on the pharmacokinetics of raltegravir, due to dosage of 1200 mg raltegravir in HIV-infected participants already taking 400 mg raltegravir twice daily as part of their HIV treatment regimen.

Conditions

HIV Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Raltegravir Pre- and 4 Period Sequence

Starting five days prior to Period 1 participants will be treated with 1200 mg raltegravir, once daily for five days. In Period 1 participants will be treated with 1200 raltegravir alone; this is followed by Period 2 where participants will be treated with 1200 mg raltegravir and TUMS concomitantly; this is followed by Period 3 where participants will be treated with 1200 mg raltegravir and 12 hours later with Leader Antacid; followed by Period 4 where participants will be treated with 1200 mg raltegravir and 12 hours later with TUMS. The wait between Periods is 2-7 days.

Group Type: EXPERIMENTAL

Raltegravir 1200 mg

Intervention Type: DRUG

Two tablets of 600 mg raltegravir administered orally, once daily, over 5 days of Pre-treatment, and once at the start of Periods 1-4.

TUMS

Intervention Type: DRUG

Three tablets of TUMS Ultra Strength (US) 1000, taken orally, concomitantly with raltegravir in Period 2, and 12 hours after raltegravir in Period 4

Leader Antacid

Intervention Type: DRUG

20 mL Leader Antacid Maximum Strength (MS) taken orally 12 hours after raltegravir, in Period 3

Interventions

Raltegravir 1200 mg

Two tablets of 600 mg raltegravir administered orally, once daily, over 5 days of Pre-treatment, and once at the start of Periods 1-4.

Intervention Type: DRUG

TUMS

Three tablets of TUMS Ultra Strength (US) 1000, taken orally, concomitantly with raltegravir in Period 2, and 12 hours after raltegravir in Period 4

Intervention Type: DRUG

Leader Antacid

20 mL Leader Antacid Maximum Strength (MS) taken orally 12 hours after raltegravir, in Period 3

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Is HIV positive
• Is on a stable raltegravir-containing (400 mg every 12hr) antiretroviral (ARV) regimen for at least 1 month prior to study entry, with no changes, including dose adjustments; and agrees to maintain their current ARV therapy throughout the study.
• Be male, or a non-pregnant and non-breast feeding female at least 18 years of age at the pre-trial (screening)
• Has a Body Mass Index (BMI) =< 32 kg/m^2

Exclusion Criteria

• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases (excluding HIV)
• Has a history of gastric bypass surgery
• Has a history of cancer (malignancy)
• Has a history of chronic diarrhea within approximately 3 months prior to the pre-trial visit
• Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-trial visit
• Has participated in another investigational trial within 4 weeks prior to the pre-trial visit
• Is currently taking rifampin or atazanavir or is unable to refrain from the use of 1) any proton pump inhibitor from two weeks prior to the study through the completion of Period 4, and 2) any H2-blockers, over-the-counter antacids, calcium supplements or multivitamins from one week prior to the study through the completion of Period 4
• Consumes greater than 3 glasses of alcoholic beverages or distilled spirits per day
• Consumes greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
• Is currently a regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months of screening

• 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

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Krishna R, East L, Larson P, Valiathan C, Butterfield K, Teng Y, Hernandez-Illas M. Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir. J Pharm Pharmacol. 2016 Nov;68(11):1359-1365. doi: 10.1111/jphp.12632. Epub 2016 Sep 27.

Reference Type: RESULT

PMID: 27671833 (View on PubMed)

Other Identifiers

0518-824

Identifier Type: -

Identifier Source: org_study_id