HIV InfectionPhase 1NCT01275443
Study in Healthy Volunteers of the Safety and Metabolism of Different Doses of the Anti-HIV Drug TMC278LA.
A Phase 1 study testing 300mg TMC278LA, 150mg TMC278LA and 1200mg TMC278LA in people with HIV Infection, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
TMC278 (also called rilpivirine) is a new drug being developed to treat HIV. Usually TMC278 is taken as a tablet, by mouth, once a day, but a 'long acting' formulation has been developed so the drug stays in the bloodstream for a longer time - this allows the drug to be given by injection and less often. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infection
- What is being tested?
- 300mg TMC278LA, 150mg TMC278LA and 1200mg TMC278LA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2011to Jun 2012
- 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 to 50 years
- All sexes
- Healthy volunteers accepted
- 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 trial requirements.
- Non-pregnant, non-lactating females (at least 40% will be of self-identified African ancestry)
- Age between 18 to 50 years, inclusive.
- Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.
- Negative antibody/antigen combined test for HIV1 and HIV2.
- Absence of any significant health problems (in the opinion of the investigator) on the basis of the screening procedures; including medical history, physical examination, vital signs, ECG.
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- Willing to undergo HIV testing, HIV discussion and receive HIV test results throughout the trial (according to the "UK National Guidelines for HIV Testing 2008", www.bhiva.org).
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception (intrauterine device, condoms, anatomical sterility in self or partner) to avoid pregnancy throughout the trial and for a period of at least four months after the trial follow up visit (oral hormonal methods and implant contraceptives are allowed but only in combination with the additional protection of a barrier method). Males participating in sexual intercourse that could result in pregnancy must use condoms during the duration of the study and for up to four months following the follow up visit.
- Willing to abstain from sexual intercourse (vaginal for females and receptive anal for males) for 48 hours prior to each trial visit (with complete abstinence in the first 28 days post-dose).
- Females willing to refrain from the use of vaginal products or objects including, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 14 days prior to enrolment and for the duration of the trial. Males willing to refrain from the use of anal products or objects including douches, lubricants and vibrators/dildos for 14 days prior to enrolment and for the duration of the trial.
- Likely to remain resident in the UK for the duration of the trial period.
- Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database.
- Willing to provide photographic identification at each visit.
- Registered with a GP in the UK
Who cannot join
- Any significant acute or chronic medical illness.
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
- Positive blood screen for syphilis, hepatitis A (IgM) B (HBs Ag) and/or C antibodies.
- Positive blood screen for HIV-1 and/or HIV-2 antibodies.
- Positive screen for sexually transmitted infections at screening visit (if bacterial vaginosis or candidiasis detected at screen, these may be treated with test-of-cure prior to enrolment).
- Prolonged QT interval on screening ECG, or clinically significant change as judged by investigator.
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- High-risk behaviour for HIV infection which is defined as having one of the following within six months before trial day 0 (first dose):
- had unprotected vaginal or anal sex with a known HIV infected person or a casual partner.
- engaged in sex work for money or drugs. iii. acquired a sexually transmitted disease. iv. having a high risk partner either currently or in the previous six months
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events.
- Exposure to any investigational drug or placebo within 30 days of first dose of trial drug (additional check to be made on TOPS www.tops.org.uk).
- History of severe drug allergy that in the opinion of the Investigator may increase the risk of developing an allergic reaction to the trial drug.
- Use of any drug, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of trial drug (unless approved or prescribed by the Investigator (for exceptions see section 5.2).
- Females who are pregnant or breast-feeding..
- Clinically significant laboratory abnormalities (according to normal range as defined by central laboratory).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacokinetic Evaluation of the Exposure and Distribution of TMC278LA for Use as Pre-exposure Prophylaxis, in Plasma and Genital Tract / Rectal Compartments, Following a Single Intramuscular Dose at Different Doses in HIV-negative Healthy Volunteers.
TMC278 (also called rilpivirine) is a new drug being developed to treat HIV. Usually TMC278 is taken as a tablet, by mouth, once a day, but a 'long acting' formulation has been developed so the drug stays in the bloodstream for a longer time - this allows the drug to be given by injection and less often. It is hoped that this injectable version of the drug may be used to help prevent HIV transmission in the future by giving it to people who are at risk of HIV. This is similar to the way travellers to areas with malaria may take antibiotics to prevent infection. The investigators aim to investigate the feasibility of using TMC278 as a preventative medication by performing this study.
The purpose of this study is to investigate the levels of drug which can be measured in the blood, as well as the tissues and fluids of the rectum (the lowest part of the bowels just before the opening of the anus) as well as the safety of the drug and how well tolerated it is when given as a single dose. In this study, the investigators will not be investigating whether the drug prevents HIV so the investigators will recruit people who are HIV negative, and whose lifestyle does not put them at risk of becoming infected before or during the study.
If the study shows the drug is well tolerated and produces appropriate levels of the drug (in the bloodstream and the rectal compartment) to suggest that it could be effective, it will help design future studies looking at preventing HIV.
Read the detailed description
The trial will examine the pharmacokinetics of doses of 300mg and 600mg, as well as either 150mg or 1200mg, of TMC278LA, given as a single intramuscular dose to HIV-negative participants. Investigation of drug pharmacokinetics in plasma, female genital secretions and tissue samples, and male rectal fluid and tissue samples (at the 600mg dose) will be also carried out in order to provide data on relative drug exposure following drug administration. Additionally, ex-vivo assays to assess viral inhibition in fluid from genital secretions and rectal compartments will provide partial information on pharmacodynamic characteristics of TMC278; this may usefully inform future selection decisions on the appropriate target concentrations required for prevention.
The target concentration for a prophylactic use of TMC278 in plasma, genital or rectal tissues and fluids is unknown. It is possible that a target lower than that required for treatment of established infection would be suitable. However, there is currently no pharmacodynamic data to usefully inform what this target concentration might be. In the absence of population PK data in an efficacy trial of TMC278 as a prophylactic agent, the investigators aim to obtain useful indirect data from ex-vivo viral inhibition assays to at least guide future decisions on dose selection.
Up to 60 evaluable female participants will be enrolled, with more than 40% being of African ancestry. Six male participants will also be enrolled. This will provide data on plasma pharmacokinetics and the relative distribution kinetics in the female genital tract and male rectal compartment in order to support expanded safety studies and a phase III global efficacy trial.
- Conditions
- HIV Infection
- Being tested
- 300mg TMC278LA, 150mg TMC278LA, 1200mg TMC278LA, 600mg TMC278LA
- Keywords
- HIV
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
300mg TMC278LADrug
Also called rilpivirine long-acting
300mg TMC278LA intramuscular injection
150mg TMC278LADrug
Also called rilpivirine long-acting
150mg TMC278LA intramuscular injection
1200mg TMC278LADrug
Also called rilpivirine long-acting
1200mg TMC278LA intramuscular injection
600mg TMC278LADrug
Also called rilpivirine long-acting
600mg TMC278LA intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| 300mg TMC278LA | Experimental | Single gluteal intramuscular injection (300mg) at day 1 Receives: Drug: 300mg TMC278LA |
| 1200mg TMC278LA | Experimental | Single gluteal intramuscular injection (1200mg) at day 1 Receives: Drug: 1200mg TMC278LA |
| 600mg TMC278LA | Experimental | Single gluteal intramuscular injection (600mg) at day 1 Receives: Drug: 600mg TMC278LA |
| 150mg TMC278LA | Experimental | This arm was included in the adaptive design of the study, but was not recommended for use based on the review of results from 300mg and 600mg arms by the protocol steering committee Receives: Drug: 150mg TMC278LA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma pharmacokinetics
The plasma pharmacokinetics of TMC278LA at different dose levels up to 84 days after a single intramuscular administration
Measured: 84 days
TMC278LA concentrations in the genital tract and rectal compartments.
TMC278LA concentrations in the genital tract and rectal compartments following the administration of different doses in HIV-negative healthy volunteers.
Measured: 84 days
Secondary outcomes (2)
Safety and tolerability of TMC278LA
The safety and tolerability of up to four different doses of TMC278LA administered as a single dose intramuscularly assessed by clinical and laboratory tests and adverse event reporting
Measured: 84 days
HIV replication in vitro
The effect of the genital and rectal fluid drug concentrations on HIV replication in vitro (pharmacodynamic [PD] analysis)
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJun 2012
- Study completionJun 2012
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 HIV InfectionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, Dr, Principal investigator, St Stephen's AIDS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275443
- Sponsor's protocol ID
- SSAT 040
- Status last verified
- Jun 2017
- First submitted
- 11 Jan 2011
- Last updated
- 26 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Jackson AG, Else LJ, Mesquita PM, Egan D, Back DJ, Karolia Z, Ringner-Nackter L, Higgs CJ, Herold BC, Gazzard BG, Boffito M. A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. Clin Pharmacol Ther. 2014 Sep;96(3):314-23. doi: 10.1038/clpt.2014.118. Epub 2014 May 26.
PubMed 24862215
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Evaluation of the Exposure and Distribution of TMC278LA for Use as Pre-exposure Prophylaxis, in Plasma and Genital Tract / Rectal Compartments, Following a Single Intramuscular Dose at Different Doses in HIV-negative Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01275443
- Acronym / sponsor ID
- SSAT 040
- Conditions
- HIV Infection
- Keywords
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 12 Jan 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.
TMC278 (also called rilpivirine) is a new drug being developed to treat HIV. Usually TMC278 is taken as a tablet, by mouth, once a day, but a 'long acting' formulation has been developed so the drug stays in the bloodstream for a longer time - this allows the drug to be given by injection and less often. It is hoped that this injectable version of the drug may be used to help prevent HIV transmission in the future by giving it to people who are at risk of HIV. This is similar to the way travellers to areas with malaria may take antibiotics to prevent infection. The investigators aim to investigate the feasibility of using TMC278 as a preventative medication by performing this study.
The purpose of this study is to investigate the levels of drug which can be measured in the blood, as well as the tissues and fluids of the rectum (the lowest part of the bowels just before the opening of the anus) as well as the safety of the drug and how well tolerated it is when given as a single dose. In this study, the investigators will not be investigating whether the drug prevents HIV so the investigators will recruit people who are HIV negative, and whose lifestyle does not put them at risk of becoming infected before or during the study.
If the study shows the drug is well tolerated and produces appropriate levels of the drug (in the bloodstream and the rectal compartment) to suggest that it could be effective, it will help design future studies looking at preventing HIV.
Detailed description
The trial will examine the pharmacokinetics of doses of 300mg and 600mg, as well as either 150mg or 1200mg, of TMC278LA, given as a single intramuscular dose to HIV-negative participants. Investigation of drug pharmacokinetics in plasma, female genital secretions and tissue samples, and male rectal fluid and tissue samples (at the 600mg dose) will be also carried out in order to provide data on relative drug exposure following drug administration. Additionally, ex-vivo assays to assess viral inhibition in fluid from genital secretions and rectal compartments will provide partial information on pharmacodynamic characteristics of TMC278; this may usefully inform future selection decisions on the appropriate target concentrations required for prevention.
The target concentration for a prophylactic use of TMC278 in plasma, genital or rectal tissues and fluids is unknown. It is possible that a target lower than that required for treatment of established infection would be suitable. However, there is currently no pharmacodynamic data to usefully inform what this target concentration might be. In the absence of population PK data in an efficacy trial of TMC278 as a prophylactic agent, the investigators aim to obtain useful indirect data from ex-vivo viral inhibition assays to at least guide future decisions on dose selection.
Up to 60 evaluable female participants will be enrolled, with more than 40% being of African ancestry. Six male participants will also be enrolled. This will provide data on plasma pharmacokinetics and the relative distribution kinetics in the female genital tract and male rectal compartment in order to support expanded safety studies and a phase III global efficacy trial.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 300mg TMC278LA | Experimental | Drug: 300mg TMC278LASingle gluteal intramuscular injection (300mg) at day 1 |
| 1200mg TMC278LA | Experimental | Drug: 1200mg TMC278LASingle gluteal intramuscular injection (1200mg) at day 1 |
| 600mg TMC278LA | Experimental | Drug: 600mg TMC278LASingle gluteal intramuscular injection (600mg) at day 1 |
| 150mg TMC278LA | Experimental | Drug: 150mg TMC278LAThis arm was included in the adaptive design of the study, but was not recommended for use based on the review of results from 300mg and 600mg arms by the protocol steering committee |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 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 trial requirements.
- Non-pregnant, non-lactating females (at least 40% will be of self-identified African ancestry)
- Age between 18 to 50 years, inclusive.
- Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.
- Negative antibody/antigen combined test for HIV1 and HIV2.
Key exclusion criteria (15 listed)
- Any significant acute or chronic medical illness.
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
- Positive blood screen for syphilis, hepatitis A (IgM) B (HBs Ag) and/or C antibodies.
- Positive blood screen for HIV-1 and/or HIV-2 antibodies.
- Positive screen for sexually transmitted infections at screening visit (if bacterial vaginosis or candidiasis detected at screen, these may be treated with test-of-cure prior to enrolment).
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 |
|---|---|---|
| 300mg TMC278LAAlso: rilpivirine long-acting300mg TMC278LA intramuscular injection | Drug | 300mg TMC278LA |
| 150mg TMC278LAAlso: rilpivirine long-acting150mg TMC278LA intramuscular injection | Drug | 150mg TMC278LA |
| 1200mg TMC278LAAlso: rilpivirine long-acting1200mg TMC278LA intramuscular injection | Drug | 1200mg TMC278LA |
| 600mg TMC278LAAlso: rilpivirine long-acting600mg TMC278LA intramuscular injection | Drug | 600mg TMC278LA |
Primary outcome
Plasma pharmacokinetics
Time frame: 84 days
The plasma pharmacokinetics of TMC278LA at different dose levels up to 84 days after a single intramuscular administration
TMC278LA concentrations in the genital tract and rectal compartments.
Time frame: 84 days
TMC278LA concentrations in the genital tract and rectal compartments following the administration of different doses in HIV-negative healthy volunteers.
2 secondary outcomes
Safety and tolerability of TMC278LA
Time frame: 84 days
HIV replication in vitro
Time frame: 84 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 26 Jun 2017.
- Results publication: PubMed 24862215Jackson AG, Else LJ, Mesquita PM, Egan D, Back DJ, Karolia Z, Ringner-Nackter L, Higgs CJ, Herold BC, Gazzard BG, Boffito M. A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. Clin Pharmacol Ther. 2014 Sep;96(3):314-23. doi: 10.1038/clpt.2014.118. Epub 2014 May 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.
Marta Boffito, Dr principal investigator
St Stephen's AIDS Trust
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 300mg TMC278LA, 150mg TMC278LA and 1200mg TMC278LA in people with HIV Infection, run by St Stephens Aids Trust 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 14 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 26 Jun 2017. 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?
Plasma pharmacokinetics (time frame: 84 days). The study lists 2 primary outcomes in all. 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 NCT01275443, 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 26 Jun 2017.