Raltegravir and Calcium Supplementation Interaction in HIV Treatment

(RCPK Trial)

Overseen By CIU Clinical Investigation Unit

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: Antiretrovirals

Must not be taking: Micronutrients, Minerals

Disqualifiers: BMI > 30, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the HIV medication raltegravir (also known as Isentress or Isentress HD) interacts with calcium supplements when taken together. Researchers aim to determine if simultaneous intake affects raltegravir levels in the body. Suitable candidates for this study are healthy individuals managing HIV with stable treatment, maintaining a very low viral load (less than 50 copies/mL), and able to manage their medication schedule as required. Participants must commit to several monitoring visits and agree to temporarily discontinue herbal products. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for more patients, offering participants an opportunity to contribute to valuable research.

Will I have to stop taking my current medications?

You can continue your current HIV treatment, but you must stop using any herbal or natural health products for 2 weeks before the study and during it. You also cannot take any medications that might affect the study drugs, except for oral contraception and your stable HIV treatment.

What is the safety track record for Raltegravir and Calcium?

Research shows that raltegravir, a drug for treating HIV, is usually well-tolerated by patients. In past studies, common side effects included headache, nausea, and diarrhea. Although serious skin reactions like Stevens-Johnson syndrome have been reported, they remain rare.

Raltegravir is often combined with other HIV drugs and has been safely used by many patients. The FDA has approved it, indicating it has passed strict safety tests for its intended use.

This study tests raltegravir with calcium carbonate, a common antacid. While specific safety data for this combination is not available, both are widely used and generally safe when taken as directed.

Participants should always inform the study team about any unusual symptoms. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about exploring the interaction between raltegravir and calcium supplementation in HIV treatment. Unlike other antiretroviral treatments that may not consider interactions with common supplements, this study focuses on understanding how calcium carbonate, a regularly used antacid, affects raltegravir, a key integrase inhibitor. By investigating this interaction, researchers aim to optimize dosing and ensure that patients can safely use both treatments without compromising the effectiveness of raltegravir in managing HIV.

What evidence suggests that raltegravir and calcium supplementation could be effective in HIV treatment?

Studies have shown that raltegravir effectively treats HIV. For instance, the ONCEMRK study found that 81.5% of patients taking a once-daily dose of raltegravir experienced a significant reduction in the virus in their blood after 96 weeks. Raltegravir is generally well-tolerated, with no serious side effects reported in several studies. However, taking raltegravir with calcium carbonate can lower the drug's level in the blood by about 32%. This trial will investigate this interaction by measuring the pharmacokinetics of raltegravir when taken alone and with calcium carbonate, which might affect its efficacy. ^{6 7 8 9 10}

Who Is on the Research Team?

Bill Cameron, MD

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for healthy HIV-infected men and women aged 18-65, with a stable viral load under 50 copies/mL. They must be on effective antiretroviral therapy that's compatible with the study drugs or can be timed around them. Participants need to avoid herbal products two weeks before and during the study.

Inclusion Criteria

I am on a stable HIV treatment that fits with the study's medication schedule.

I am HIV positive but otherwise healthy.

I am willing to stop taking herbal or natural products 2 weeks before and during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period 1

Participants take raltegravir 1200 mg alone daily for 7 days with serial PK measures

1 week

2 visits (in-person)

Treatment Period 2

Participants take raltegravir 1200 mg with 500 mg calcium carbonate daily for 7 days with serial PK measures

1 week

2 visits (in-person)

Treatment Period 3

Participants take raltegravir 1200 mg with 1000 mg calcium carbonate daily for 7 days with serial PK measures

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Calcium
• Raltegravir

Trial Overview The trial tests how taking calcium carbonate (an antacid) affects the levels of Raltegravir, an HIV medication, in the blood when they are taken together. The goal is to see if calcium changes how well Raltegravir works.

How Is the Trial Designed?

Group I: Raltegravir-Calcium PK measure Experimental Treatment 2 Interventions

Period 1: Raltegravir 1200 mg alone; Period 2: Calcium carbonate antacid 500 mg and 1200 mg of raltegravir given concomitantly; Period 3: two tablets of calcium carbonate antacid 500 mg and 1200 mg of raltegravir given concomitantly. Patients will have a total of 8 visits during the study. Day 1 visit: Raltegravir 1200 mg oral daily until day 7. Day 7 visit: Timed serial phlebotomy before dosing t(0) and 0.5, 1, 1.5, 2, 3, 4, 6 hours after observed dosing. Day 8 visit: 24 h PK sampling followed by Raltegravir 1200 mg + Calcium carbonate 500 mg oral daily until day 14. Day 14 visit: Timed serial phlebotomy before dosing t(0) and 0.5, 1, 1.5, 2, 3, 4, 6 hours after observed dosing. Day 15 visit: 24 h PK Sampling followed by Raltegravir 1200 mg + Calcium carbonate 1000 mg oral daily until day 21. Day 21 visit: Timed serial phlebotomy before dosing t(0) and 0.5, 1, 1.5, 2, 3, 4, 6 hours after observed dosing. Day 22 visit: 24 h PK Sampling. Day 51 visit: Final safety visit.

Raltegravir is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Isentress for:

• HIV infection in adults and children

Approved in European Union as Isentress for:

• HIV infection in adults and children

Approved in United States as Isentress HD for:

• HIV infection in adults and children weighing at least 40 kg

Approved in United Kingdom as Raltegravir for:

• HIV infection in adults and pediatric patients weighing at least 40 kg

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12228467/

Influence of concurrent oral calcium carbonate ... Patiño Escarcina JE, Netto EM, Brites C. Long-term outcomes of highly experienced people with HIV undergoing salvage therapy with raltegravir.

2. hivclinic.ca hivclinic.ca/wp-content/plugins/php/app3.php?r=4&c=calcium

Raltegravir & Calcium When calcium carbonate antacid 3000 mg single dose was given with raltegravir 400 mg BID, raltegravir Cmin was decreased by 32%. This interaction was not ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40617620/

Influence of concurrent oral calcium carbonate ... This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral ...

4. merck.com merck.com/news/merck-announces-week-96-results-from-oncemrk-a-study-evaluating-once-daily-isentress-hd-raltegravir-in-combination-with-other-antiretroviral-agents-for-the-treatment-of-hiv-1-infection-in-a/

Merck Announces Week 96 Results from ONCEMRK, A ... Week 96 data from the ONCEMRK study showed that 81.5 percent of the 531 patients taking once-daily ISENTRESS HD 1200 mg (2 x 600 mg) achieved viral suppression ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/perinatal-hiv/safety-toxicity-arv-agents-integrase-inhibitors-raltegravir-isentress-perinatal.pdf

Raltegravir (Isentress, Isentress HD, RAL) In the P1026s study, P1081 study, and PANNA study, RAL was well tolerated, with no treatment- related serious adverse events observed in ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/022145s044,203045s017,205786s009lbl.pdf

Isentress - accessdata.fda.gov The safety of ISENTRESS was evaluated in HIV-infected treatment-naïve subjects in 2 Phase III studies: STARTMRK evaluated ISENTRESS 400 mg twice daily versus ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/raltegravir-oral-route/description/drg-20071335

Raltegravir (oral route) - Side effects & dosage Raltegravir will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/022145s029lbl.pdf

Isentress (raltegravir) tablets label - accessdata.fda.gov Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome,.

9. webmd.com webmd.com/drugs/2/drug-149324-1036/isentress-oral/raltegravir-oral/details

Isentress (raltegravir) - Uses, Side Effects, and More Interactions · There are no known interactions between Isentress and foods or drinks. · It is unknown if drinking alcohol will affect Isentress. · Always tell your ...

10. pdf.hres.ca pdf.hres.ca/dpd_pm/00073112.PDF

isentress ISENTRESS HD® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients weighing ...