Calcium Supplementation in HIV Patients Using RaltegravirPhase 4RCPKNCT04258475
The Influence of Concurrent Oral Calcium Carbonate Supplementation on Steady State Pharmacokinetics of Oral Raltegravir.
A Phase 4 study testing Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily. and Calcium carbonate antacid tablet in people with Calcium Supplementation in HIV Patients Using Raltegravir, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Calcium Supplementation in HIV Patients Using Raltegravir
- What is being tested?
- Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily. and Calcium carbonate antacid tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 9 Dec 2020to 1 Jan 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be a healthy HIV infected male or female.
- Patient must be between the ages of 18 and 65.
- Patient must be undergoing stable effective ART and must be compatible with once a-day study raltegravir or be separable from study calcium co-administration by at least 8 hours in a twice-a-day dosing schedule.
- Patient must have a viral load < 50 copies/mL within 3 months of study Day 1.
- Patient must be medically stable at time of study, with no evidence of acute illness as per physician assessment.
- Patient must be able to read, understand and sign a written informed consent prior to initiation of the study.
- Patients must be willing to stop using any herbal or natural health products for 2 weeks prior to Day 1 and during the study.
Who cannot join
- Patient on any medications that can alter the drug absorption of study medications other than oral contraception and stable effective ART. This includes no micronutrient mineral and trace element supplementation (except calcium).
- Patient donated blood with the 30 days prior to study start.
- Persons with prior gastric or enteric surgery, acute medical illness, or anticipated use of other medications, supplements or treatments.
- Patient has a BMI > 30
- Patient is unable to understand, consent and adhere to study protocol and procedures.
- Women who are pregnant, breast-feeding, and not willing to practice contraception during the study period plus one month.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
The Ottawa Hospital General Campus
Ottawa, Ontario, K1H 8L6
Nancy Tremblay, RN, 613-737-8899 ext. 71893, nantremblay@toh.ca
Bill Cameron, M.D
About this study
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.
Read the 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).
- Being tested
- Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily., Calcium carbonate antacid tablet
- Keywords
- Raltegravir, Calcium, PK
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily.Drug
Also called RAL, Isentress®
Raltegravir will be dosed in a fasted state in all periods. Participants will take Raltegravir along with other ART medication.
Calcium carbonate antacid tabletDrug
Also called TUMS® Ultra Strength (US) 500 mg
PK analysis of different doses of calcium carbonate antacid in patients undergoing ART treatment for HIV using Raltegravir.
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir-Calcium PK measure | Experimental | 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. Receives: Drug: Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily.; Drug: Calcium carbonate antacid tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-state serum pharmacokinetics analysis of raltegravir in patients undergoing ART treatment (with raltegravir) and concurrent calcium supplementation.
Determine the minimum (C24h) serum concentration in the steady state of raltegravir 24 hours after dosing of raltegravir 1200 mg alone and when administered concomitantly with calcium carbonate 500 mg or 1000 mg.
Measured: 22 days
Secondary outcomes (5)
Time to peak maximum plasma concentration PK parameter analysis within study duration.
To determine other pharmacokinetic measures including time from observed dosing to maximum plasma concentration, under the same conditions as the primary objectives.
Measured: 22 days
Maximum concentration PK parameter analysis within study duration.
To determine pharmacokinetic measure of maximum concentration under the same conditions as the primary objectives.
Measured: 22 days
Area-under-the-time-concentration curve from 0 to 24 hours PK parameter analysis within study duration.
To determine pharmacokinetic measure of area-under-the-time-concentration curve from 0 to 24 hours under the same conditions as the primary objectives.
Measured: 22 days
Elimination half-life PK parameter analysis within study duration.
To determine pharmacokinetic measure of elimination half-life under the same conditions as the primary objectives.
Measured: 22 days
24-hour concentration (Cmin, Ctrough) of raltegravir PK parameter analysis within study duration within study duration.
To determine pharmacokinetic measure of the 24-hour concentration (Cmin, Ctrough) of raltegravir under the same conditions as the primary objectives.
Measured: 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start9 Dec 2020
- Primary completion15 Jun 2024 (estimated)
- Study completion1 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Calcium Supplementation in HIV Patients Using RaltegravirStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bill Cameron, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04258475
- Sponsor's protocol ID
- 20190750-01H
- Acronym
- RCPK
- Status last verified
- Nov 2023
- First submitted
- 3 Feb 2020
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share IPD
Publications
Teixeira Nunes Porto LL, Doyle MA, Zhang G, Tremblay N, Yazji B, Kanji S, Cameron DW. Influence of concurrent oral calcium carbonate supplementation on steady-state pharmacokinetics of once daily oral raltegravir in persons with HIV: a protocol for a prospective open-label non-randomised study in Canada. BMJ Open. 2025 Jul 5;15(7):e094384. doi: 10.1136/bmjopen-2024-094384.
PubMed 40617620
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Concurrent Oral Calcium Carbonate Supplementation on Steady State Pharmacokinetics of Oral Raltegravir.
- ClinicalTrials.gov ID
- NCT04258475
- Acronym / sponsor ID
- RCPK / 20190750-01H
- Keywords
- Raltegravir, Calcium, PK
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 9 Dec 2020 (actual)
- Primary completion
- 15 Jun 2024 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 6 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Raltegravir-Calcium PK measure | Experimental | Drug: Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily., Drug: Calcium carbonate antacid tabletPeriod 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient must be a healthy HIV infected male or female.
- Patient must be between the ages of 18 and 65.
- Patient must be undergoing stable effective ART and must be compatible with once a-day study raltegravir or be separable from study calcium co-administration by at least 8 hours in a twice-a-day dosing schedule.
- Patient must have a viral load < 50 copies/mL within 3 months of study Day 1.
- Patient must be medically stable at time of study, with no evidence of acute illness as per physician assessment.
Key exclusion criteria (6 listed)
- Patient on any medications that can alter the drug absorption of study medications other than oral contraception and stable effective ART. This includes no micronutrient mineral and trace element supplementation (except calcium).
- Patient donated blood with the 30 days prior to study start.
- Persons with prior gastric or enteric surgery, acute medical illness, or anticipated use of other medications, supplements or treatments.
- Patient has a BMI > 30
- Patient is unable to understand, consent and adhere to study protocol and procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily.Also: RAL, Isentress®Raltegravir will be dosed in a fasted state in all periods. Participants will take Raltegravir along with other ART medication. | Drug | Raltegravir-Calcium PK measure |
| Calcium carbonate antacid tabletAlso: TUMS® Ultra Strength (US) 500 mgPK analysis of different doses of calcium carbonate antacid in patients undergoing ART treatment for HIV using Raltegravir. | Drug | Raltegravir-Calcium PK measure |
Primary outcome
Steady-state serum pharmacokinetics analysis of raltegravir in patients undergoing ART treatment (with raltegravir) and concurrent calcium supplementation.
Time frame: 22 days
Determine the minimum (C24h) serum concentration in the steady state of raltegravir 24 hours after dosing of raltegravir 1200 mg alone and when administered concomitantly with calcium carbonate 500 mg or 1000 mg.
5 secondary outcomes
Time to peak maximum plasma concentration PK parameter analysis within study duration.
Time frame: 22 days
Maximum concentration PK parameter analysis within study duration.
Time frame: 22 days
Area-under-the-time-concentration curve from 0 to 24 hours PK parameter analysis within study duration.
Time frame: 22 days
Elimination half-life PK parameter analysis within study duration.
Time frame: 22 days
24-hour concentration (Cmin, Ctrough) of raltegravir PK parameter analysis within study duration within study duration.
Time frame: 22 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Derived from this study: PubMed 40617620Teixeira Nunes Porto LL, Doyle MA, Zhang G, Tremblay N, Yazji B, Kanji S, Cameron DW. Influence of concurrent oral calcium carbonate supplementation on steady-state pharmacokinetics of once daily oral raltegravir in persons with HIV: a protocol for a prospective open-label non-randomised study in Canada. BMJ Open. 2025 Jul 5;15(7):e094384. doi: 10.1136/bmjopen-2024-094384.
- Individual participant dataSharing planned: No. No plan to share IPD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bill Cameron, MD principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Raltegravir standard dosage of 1200 mg (two 600 mg tablets) orally once daily. and Calcium carbonate antacid tablet in people with Calcium Supplementation in HIV Patients Using Raltegravir, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact CIU Clinical Investigation Unit (613-737-8811 ext. 78304, CIU@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Steady-state serum pharmacokinetics analysis of raltegravir in patients undergoing ART treatment (with raltegravir) and concurrent calcium supplementation. (time frame: 22 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04258475, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.