NCT04258475

The Influence of Concurrent Oral Calcium Carbonate Supplementation on Steady State Pharmacokinetics of Oral Raltegravir.

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Ottawa Hospital Research Institute · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to measure change in raltegravir serum pharmacokinetics in steady state, when co-administered with calcium carbonate formulated as antacid.

Detailed description

Raltegravir (Isentress®) is a familiar, well-tolerated oral HIV integrase inhibitor drug. This class of HIV integrase inhibitor drug is a preferred component of combination anti-retroviral therapy (ART). Calcium supplementation is sometimes recommended for persons with HIV due to risk of bone mineral density loss associated with aging and with other medications, including ART. Due to the chemical structure of raltegravir, which contains two metal-binding motifs, drug-drug interactions can occur when co-administered with divalent metal cations. This interaction can lead to the chelation of the drug and a reduction in drug absorption. Previous work reported a notable decrease in oral absorption when raltegravir was administered concomitantly with a 3,000 mg dose of calcium carbonate antacid. Given that current standard daily calcium typically consists of 1000 mg elemental calcium, the proposed study will investigate the impact of a lower dose (500 and 1,000 mg) of calcium carbonate antacid as TUMS® on the pharmacokinetics of a 1200 mg raltegravir once daily dose. The patient population will consist of volunteers who are taking ART with good virological and immunological effect, and are willing and able to separate once-daily ART dosing from study medications of raltegravir and calcium, by taking other medications in the evening and study medications in the morning, at least 8 hours apart. This study consists of three periods: Period 1) Each study participant will take two oral raltegravir 600 mg tablets with breakfast once daily alone for 7 days and have serial PK measures of drug levels from serial phlebotomies over 6 hours and at 24-hour follow-up prior to next daily dosage. Period 2) Starting day 8, participants will take the two raltegravir 600 mg tablets orally concurrent with 500 mg calcium carbonate antacid daily, and similarly have PK as on days 7/8 prior, on days 14/15. Period 3) Starting on day 15, participants will take the two tablets of raltegravir 600 mg concurrent with 1,000 mg calcium carbonate antacid daily and have PK as before on days 21/22. The primary objective of this study is to measure and compare the minimum serum concentration of raltegravir at 24 hours (C24h) from daily dosing in the steady state, after raltegravir administration alone, and with calcium carbonate 500 mg and 1000 mg. A secondary objective is to determine full serum pharmacokinetic measures, for area-under-the-time-concentration curve from 0 to 24 (AUC0-24h) hours, time to and maximum concentration (Tmax and Cmax) and elimination half-life (t1/2).

Conditions

• Calcium Supplementation in HIV Patients Using Raltegravir

Interventions

Type	Name	Description
DRUG	Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily.	Raltegravir will be dosed in a fasted state in all periods. Participants will take Raltegravir along with other ART medication.
DRUG	Calcium carbonate antacid tablet	PK analysis of different doses of calcium carbonate antacid in patients undergoing ART treatment for HIV using Raltegravir.

Timeline

• Start date: 2020-12-09
• Primary completion: 2024-06-15
• Completion: 2025-01-01
• First posted: 2020-02-06
• Last updated: 2023-12-12

Locations

1 site across 1 country: Canada