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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV Infection

Treatments: Drug: Raltegravir 1200 mg; Drug: TUMS; Drug: Leader Antacid

Study type: Interventional

Funder types: Industry

Identifiers

NCT02473367

0518-824

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

Raltegravir Pre- and 4 Period Sequence

Experimental group

Description:

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.

Treatment:

Drug: Raltegravir 1200 mg

Drug: TUMS

Drug: Leader Antacid