HIVPhase 1RIFRALNCT01424826
The Effect of Intermittent Rifampicin on Raltegravir
A Phase 1 study testing Raltegravir and Rifampicin in people with HIV and Tuberculosis, run by Helen Reynolds at 1 site in United Kingdom.
Trial summary
This study seeks to address the question of whether intermittent dosing of rifampicin influences the pharmacokinetics of raltegravir when co-administered. This study aims to look at what happens when rifampicin is taken 3 times a week with the standard dose and an increased dose of raltegravir. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV, Tuberculosis
- What is being tested?
- Raltegravir and Rifampicin
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2012to Jul 2013
- Phase
- Phase 1
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements.
- ≥ 18 years
- Male or female subjects
- A female may be eligible to enter and participate in the study if she:
- Is of non-child-bearing potential defined as ether post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age)or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or
- Is of child-bearing potential with a negative pregnancy test at screening and agrees to use one of the following methods of contraception to avoid pregnancy
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- Complete abstinence from intercourse from 2 weeks prior to administration of IP, throughout the study and for at least 4 weeks after discontinuation of all study medication
- Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
- Any intrauterine device (IUD) with published data showing that the expected failure rate is < 1 % per year
- Any other method with published data showing that the expected failure rate is < 1 % PER YEAR
- Hormonal contraception plus a barrier method. Hormonal contraception alone will not be considered adequate for inclusion into or participation in this study due to one of the study drugs being rifampicin.
- All subjects participating in the study will be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom)
Who cannot join
- Any significant acute or chronic medical condition
- Pregnant or lactating women
- Women of childbearing age unless using non hormonal contraception
- Males who are not using contraception
- Evidence of organ dysfunction or any clinically significant deviation from normal during screening including laboratory determinations such as abnormal LFTs
- Positive blood screen for HIV-1 and 2 antibodies
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- Positive blood screen for hepatitis B or C antibodies
- Positive IGRA screen for TB
- Current or recent (within 3 months) gastrointestinal disease
- Clinically relevant alcohol or drug use or history of alcohol or drug use that will hinder compliance with treatment, follow up procedures or evaluation of adverse effects
- Use of proton pump inhibitors
- Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug
- Consumption of grapefruit and Seville oranges or products containing grapefruit or Seville oranges within 1 week of first study drug and for the duration of the study
- Use of any other drugs including over-the-counter medications and herbal preparations, within 2 weeks prior to first dose of study drug
- Previous allergy to any of the constituents of the pharmaceuticals in this trial
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Liverpool & Broadgreen Univeristy Hospitals NHS Trust
Liverpool, L7 8XP
About this study
Official title: A Single Arm, 3 Phase Study to Determine the Effect of Intermittent Dosing of Rifampicin on the Pharmacokinetics of Raltegravir in Healthy Volunteers
This study seeks to address the question of whether intermittent dosing of rifampicin influences the pharmacokinetics of raltegravir when co-administered. This study aims to look at what happens when rifampicin is taken 3 times a week with the standard dose and an increased dose of raltegravir. This is to find out the best dose of raltegravir to take when taking rifampicin 3 times a week. The study will be conducted in 18 healthy volunteers.
Read the detailed description
The aim of this study is to optimise the dosing of raltegravir when coadministered intermittently with rifampicin. The co-administration of rifampicin and antiretrovirals (ARVs) is both complicated and problematic due to the potent induction of metabolism by rifampicin. Rifampicin induces cytochrome P450 (CYP) enzymes, which results in reduced plasma concentrations of two groups of ARVs, the protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). This pharmacokinetic interaction precludes the use of PIs and severely compromises the effectiveness of the NNRTI, nevirapine, as it potentially results in the loss of antiviral activity due to sub-therapeutic concentrations which will also lead to antiretroviral resistance.
Rifampicin also induces phase II enzymes including UDP-glucuronosyl transferase. The HIV integrase inhibitor, raltegravir, is primarily metabolised by UGT1A1 and therefore, there is the potential for a pharmacokinetic drug interaction with rifampicin. In fact, previous studies have shown a decrease in raltegravir AUC, CMAX, and C12 when co-administered with daily rifampicin. During directly observed therapy (DOTs) for TB, rifampicin is often given intermittently (e.g. 3 times a week). Although several studies have examined the interaction between raltegravir and daily rifampicin, currently there are no data regarding the pharmacokinetics of raltegravir when rifampicin is co-administered intermittently.
- Conditions
- HIV, Tuberculosis
- Being tested
- Raltegravir, Rifampicin
- Keywords
- Healthy volunteers
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
400 mg bd for minimum of 28 days and maximum 35 days
RifampicinDrug
< 50 kg 600 mg 3 times/week for a minimum of 27 days and maximum of 34 days > 50 kg 900 mg 3 times/week for a minimum of 27 days and maximum of 34 days
RaltegravirDrug
800 mg bd for 4 days
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in raltegravir area under the curve (AUC) 0-12h
Measured: Day 28 and day 33
Secondary outcomes (1)
Number of participants with adverse events
Measured: 40 days (up to + 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startJan 2012
- Primary completionJun 2013
- Study completionJul 2013
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 HIVStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helen Reynolds
- Sponsor type
- University, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Helen Reynolds, University of Liverpool
- Investigators
- Saye Khoo, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01424826
- Sponsor's protocol ID
- UoL000643
- Other IDs
- 2010-021461-73
- Acronym
- RIFRAL
- Status last verified
- Oct 2013
- First submitted
- 24 Aug 2011
- Last updated
- 31 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Reynolds HE, Chrdle A, Egan D, Chaponda M, Else L, Chiong J, Back DJ, Khoo SH. Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir. J Antimicrob Chemother. 2015 Feb;70(2):550-4. doi: 10.1093/jac/dku376. Epub 2014 Sep 26.
PubMed 25261424
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, 3 Phase Study to Determine the Effect of Intermittent Dosing of Rifampicin on the Pharmacokinetics of Raltegravir in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01424826
- Acronym / sponsor ID
- RIFRAL / UoL000643
- Conditions
- HIV, Tuberculosis
- Keywords
- Healthy volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Helen ReynoldsUniversity, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust
- Study start
- Jan 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 29 Aug 2011 (estimated)
- 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.
This study seeks to address the question of whether intermittent dosing of rifampicin influences the pharmacokinetics of raltegravir when co-administered. This study aims to look at what happens when rifampicin is taken 3 times a week with the standard dose and an increased dose of raltegravir. This is to find out the best dose of raltegravir to take when taking rifampicin 3 times a week. The study will be conducted in 18 healthy volunteers.
Detailed description
The aim of this study is to optimise the dosing of raltegravir when coadministered intermittently with rifampicin. The co-administration of rifampicin and antiretrovirals (ARVs) is both complicated and problematic due to the potent induction of metabolism by rifampicin. Rifampicin induces cytochrome P450 (CYP) enzymes, which results in reduced plasma concentrations of two groups of ARVs, the protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). This pharmacokinetic interaction precludes the use of PIs and severely compromises the effectiveness of the NNRTI, nevirapine, as it potentially results in the loss of antiviral activity due to sub-therapeutic concentrations which will also lead to antiretroviral resistance.
Rifampicin also induces phase II enzymes including UDP-glucuronosyl transferase. The HIV integrase inhibitor, raltegravir, is primarily metabolised by UGT1A1 and therefore, there is the potential for a pharmacokinetic drug interaction with rifampicin. In fact, previous studies have shown a decrease in raltegravir AUC, CMAX, and C12 when co-administered with daily rifampicin. During directly observed therapy (DOTs) for TB, rifampicin is often given intermittently (e.g. 3 times a week). Although several studies have examined the interaction between raltegravir and daily rifampicin, currently there are no data regarding the pharmacokinetics of raltegravir when rifampicin is co-administered intermittently.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements.
- ≥ 18 years
- Male or female subjects
- A female may be eligible to enter and participate in the study if she:
- Is of non-child-bearing potential defined as ether post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age)or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or
Key exclusion criteria (15 listed)
- Any significant acute or chronic medical condition
- Pregnant or lactating women
- Women of childbearing age unless using non hormonal contraception
- Males who are not using contraception
- Evidence of organ dysfunction or any clinically significant deviation from normal during screening including laboratory determinations such as abnormal LFTs
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 |
|---|---|---|
| Raltegravir400 mg bd for minimum of 28 days and maximum 35 days | Drug | – |
| Rifampicin< 50 kg 600 mg 3 times/week for a minimum of 27 days and maximum of 34 days > 50 kg 900 mg 3 times/week for a minimum of 27 days and maximum of 34 days | Drug | – |
| Raltegravir800 mg bd for 4 days | Drug | – |
Primary outcome
Change in raltegravir area under the curve (AUC) 0-12h
Time frame: Day 28 and day 33
1 secondary outcome
Number of participants with adverse events
Time frame: 40 days (up to + 7 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2013.
- Derived from this study: PubMed 25261424Reynolds HE, Chrdle A, Egan D, Chaponda M, Else L, Chiong J, Back DJ, Khoo SH. Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir. J Antimicrob Chemother. 2015 Feb;70(2):550-4. doi: 10.1093/jac/dku376. Epub 2014 Sep 26.
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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.
Saye Khoo principal investigator
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Raltegravir and Rifampicin in people with HIV and Tuberculosis, run by Helen Reynolds at 1 site in United Kingdom.
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 12 inclusion and 15 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: finished, as of the sponsor's last update on 31 Oct 2013. 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 United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in raltegravir area under the curve (AUC) 0-12h (time frame: Day 28 and day 33). 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 NCT01424826, 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 31 Oct 2013.