HIVPhase 3NCT00258557
TMC114-C211: Trial of an Investigational Protease Inhibitor TMC114 With Ritonavir ("TMC114/r") in HIV-1 Infected Patients Who Have Never Been Treated With Antiretroviral Medications.
A Phase 3 study testing LPV/RTV and TMC-114/RTV in people with HIV, run by Tibotec Pharmaceuticals, Ireland at 89 sites in 25 countries.
Trial summary
The purpose of this study is to compare the efficacy, safety and tolerability of TMC114/r versus Kaletra (a combination pill of lopinavir and ritonavir, ("lpv/rtv") in HIV-1 infected patients who have never been treated with anti-retroviral medications (referred to as "treatment-naïve" patients). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- LPV/RTV and TMC-114/RTV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 692 participants
- Where
- 89 sitesin 25 countries
- Study dates
- Sep 2005to May 2012
- Phase
- Phase 3
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with documented HIV-1 infection
- Screening plasma HIV-1 RNA >= 5000 copies/mL
- Patients qualify for treatment initiation based on the investigator's assessments and/or according to treatment guidelines
- Patients who can comply with the protocol requirements
- General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.
Who cannot join
- Presence of any currently active AIDS defining illness or receiving treatment for primary HIV infection
- Life expectancy of less than 6 months
- Previous or current use of antiretroviral medications (ARVs) for the treatment of HIV-infection or hepatitis B infection with anti-HIV activity
- Female -patients who are pregnant or breast-feeding, or are of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period
- -patients with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading, or a calculated creatinine clearance (CLCr) < 70 mL/min
Trial locations and contacts
89 sites in 25 countries.
89 sites in 25 countries
United States24 sites
Study site
Baltimore, Maryland
Study site
Beverly Hills, California
Study site
Boston, Massachusetts
Study site
Brooklyn, New York
Study site
Chapel Hill, North Carolina
Study site
Columbia, South Carolina
Study site
Fort Lauderdale, Florida
Study site
Houston, Texas
Study site
Jacksonville, Florida
Study site
Las Vegas, Nevada
Study site
Long Beach, California
Study site
Los Angeles, California
Study site
Miami, Florida
Study site
Miami Beach, Florida
Study site
Orlando, Florida
Study site
Philadelphia, Pennsylvania
Study site
Phoenix, Arizona
Study site
Sacramento, California
Study site
Safety Harbor, Florida
Study site
San Francisco, California
Study site
Tampa, Florida
Study site
Vero Beach, Florida
Study site
Washington D.C., District of Columbia
Study site
Winston-Salem, North Carolina
Germany8 sites
Study site
Berlin
Study site
Cologne
Study site
Erlangen
Study site
Freiburg im Breisgau
Study site
Hamburg
Study site
Mannheim
Study site
München
Study site
Munich
Russia7 sites
Study site
Kazan'
Study site
Krasnodar
Study site
Moscow
Study site
Saint Petersburg
Study site
Smolensk
Study site
Volgograd
Study site
Voronezh
France5 sites
Study site
Bobigny
Study site
Lyon
Study site
Nice
Study site
Orléans
Study site
Paris
Australia4 sites
Study site
Brisbane
Study site
Darlinghurst
Study site
Surry Hills
Study site
Westmead
Canada4 sites
Study site
Montreal, Quebec
Study site
Ottawa, Ontario
Study site
Toronto, Ontario
Study site
Vancouver, British Columbia
Mexico4 sites
Study site
Del Tlalpan
Study site
Guadalajara
Study site
Mex Ctity
Study site
Mexico City
South Africa4 sites
Study site
Cape Town
Study site
Dundee
Study site
Johannesburg
Study site
Pretoria
Argentina3 sites
Study site
Buenos Aires
Study site
Mar del Plata
Study site
Neuquén
About this study
Official title: Phase III Randomized, Controlled, Open-label Trial to Investigate the Antiviral Activity, Tolerability and Safety of TMC114/r in Treatment- Naive HIV-1 Infected Patients.
The purpose of this study is to compare the efficacy, safety and tolerability of TMC114/r versus Kaletra (a combination pill of lopinavir and ritonavir, ("lpv/rtv") in HIV-1 infected patients who have never been treated with anti-retroviral medications (referred to as "treatment-naïve" patients).
Read the detailed description
This is a randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r) versus lpv/rtv in treatment-naive HIV-1 infected patients. Six hundred sixty treatment-naïve HIV-1 infected patients will be randomized in a 1:1 ratio to either 800/100 mg of TMC114/r once daily, or a total daily dose of 800/200 mg of lpv/rtv. All patients will take TMC114/r or lpv/rtv in combination with an NRTI background of Truvada (a combination pill of tenofovir and emtricitabine, "TDF/FTC"). The trial will consist of a screening period of approximately 14 to 28 days and a 96-week treatment period, followed by a 4-week follow-up period. The anti HIV-1 therapy initiated at baseline cannot be changed until the end of the treatment period. After the end of the treatment period (maximum of 96 weeks), patients will be followed for an additional 4 weeks to follow-up on any adverse events or laboratory abnormalities until resolution. Patients who fail either virologically or due to intolerance from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.
The primary efficacy parameter is virologic response defined as a confirmed viral load < 50 copies/mL at Week 48 the objective of this study is to establish non-inferiority of TMC114/r versus lpv/rtv in terms of virologic response at Week 48 using a non-inferiority margin of 12%. To test this hypothesis, a two-sided 95% confidence interval (CI) of the difference in response rate between TMC114/r and lpv/rtv will be derived: If the lower bound of the CI exceeds -12%, non-inferiority will be concluded. Patients will take oral doses for up to 96 weeks of either 800/100mg of TMC114/r 1x/day or 800/200mg of lpv/rtv once daily, each in combination with TDF/FTC. (The 400/100 mg 2x/day dose of lpv/rtv will be used where the 1x/day use of lpv/rtv is not approved).
- Conditions
- HIV
- Being tested
- LPV/RTV, TMC-114/RTV
- Keywords
- HIV, Anti-Retroviral agents, HIV-1, TMC114/r, Treatment naïve patients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LPV/RTVDrug
400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks
TMC-114/RTVDrug
two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks
| Study group | Role | What they receive |
|---|---|---|
| 002 | Experimental | TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks Receives: Drug: TMC-114/RTV |
| 001 | Active comparator | LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks Receives: Drug: LPV/RTV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48
Measured: 48 weeks
Secondary outcomes (1)
Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment
Measured: 192 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2005 (estimated)
- Study startSep 2005
- Primary completionJun 2007
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 692 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00258557
- Sponsor's protocol ID
- CR002800
- Other IDs
- TMC114-C211
- Status last verified
- Jun 2013
- First submitted
- 22 Nov 2005
- Last updated
- 26 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mills AM, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard PM, Workman C, Dierynck I, Sekar V, Abeele CV, Lavreys L. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009 Aug 24;23(13):1679-88. doi: 10.1097/QAD.0b013e32832d7350.
PubMed 19487905Orkin C, DeJesus E, Khanlou H, Stoehr A, Supparatpinyo K, Lathouwers E, Lefebvre E, Opsomer M, Van de Casteele T, Tomaka F. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naive patients in the ARTEMIS trial. HIV Med. 2013 Jan;14(1):49-59. doi: 10.1111/j.1468-1293.2012.01060.x. Epub 2012 Oct 23.
PubMed 23088336
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized, Controlled, Open-label Trial to Investigate the Antiviral Activity, Tolerability and Safety of TMC114/r in Treatment- Naive HIV-1 Infected Patients.
- ClinicalTrials.gov ID
- NCT00258557
- Acronym / sponsor ID
- CR002800
- Conditions
- HIV
- Keywords
- HIV, Anti-Retroviral agents, HIV-1, TMC114/r, Treatment naïve patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 692 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Sep 2005
- Primary completion
- Jun 2007 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 24 Nov 2005 (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.
The purpose of this study is to compare the efficacy, safety and tolerability of TMC114/r versus Kaletra (a combination pill of lopinavir and ritonavir, ("lpv/rtv") in HIV-1 infected patients who have never been treated with anti-retroviral medications (referred to as "treatment-naïve" patients).
Detailed description
This is a randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r) versus lpv/rtv in treatment-naive HIV-1 infected patients. Six hundred sixty treatment-naïve HIV-1 infected patients will be randomized in a 1:1 ratio to either 800/100 mg of TMC114/r once daily, or a total daily dose of 800/200 mg of lpv/rtv. All patients will take TMC114/r or lpv/rtv in combination with an NRTI background of Truvada (a combination pill of tenofovir and emtricitabine, "TDF/FTC"). The trial will consist of a screening period of approximately 14 to 28 days and a 96-week treatment period, followed by a 4-week follow-up period. The anti HIV-1 therapy initiated at baseline cannot be changed until the end of the treatment period. After the end of the treatment period (maximum of 96 weeks), patients will be followed for an additional 4 weeks to follow-up on any adverse events or laboratory abnormalities until resolution. Patients who fail either virologically or due to intolerance from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.
The primary efficacy parameter is virologic response defined as a confirmed viral load < 50 copies/mL at Week 48 the objective of this study is to establish non-inferiority of TMC114/r versus lpv/rtv in terms of virologic response at Week 48 using a non-inferiority margin of 12%. To test this hypothesis, a two-sided 95% confidence interval (CI) of the difference in response rate between TMC114/r and lpv/rtv will be derived: If the lower bound of the CI exceeds -12%, non-inferiority will be concluded. Patients will take oral doses for up to 96 weeks of either 800/100mg of TMC114/r 1x/day or 800/200mg of lpv/rtv once daily, each in combination with TDF/FTC. (The 400/100 mg 2x/day dose of lpv/rtv will be used where the 1x/day use of lpv/rtv is not approved).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 002 | Experimental | Drug: TMC-114/RTVTMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks |
| 001 | Active comparator | Drug: LPV/RTVLPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with documented HIV-1 infection
- Screening plasma HIV-1 RNA >= 5000 copies/mL
- Patients qualify for treatment initiation based on the investigator's assessments and/or according to treatment guidelines
- Patients who can comply with the protocol requirements
- General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.
Key exclusion criteria (5 listed)
- Presence of any currently active AIDS defining illness or receiving treatment for primary HIV infection
- Life expectancy of less than 6 months
- Previous or current use of antiretroviral medications (ARVs) for the treatment of HIV-infection or hepatitis B infection with anti-HIV activity
- Female -patients who are pregnant or breast-feeding, or are of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period
- -patients with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading, or a calculated creatinine clearance (CLCr) < 70 mL/min
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 |
|---|---|---|
| LPV/RTV400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks | Drug | 001 |
| TMC-114/RTVtwo 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks | Drug | 002 |
Primary outcome
Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48
Time frame: 48 weeks
1 secondary outcome
Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment
Time frame: 192 weeks
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 2013.
- Results publication: PubMed 19487905Mills AM, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard PM, Workman C, Dierynck I, Sekar V, Abeele CV, Lavreys L. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009 Aug 24;23(13):1679-88. doi: 10.1097/QAD.0b013e32832d7350.
- Derived from this study: PubMed 23088336Orkin C, DeJesus E, Khanlou H, Stoehr A, Supparatpinyo K, Lathouwers E, Lefebvre E, Opsomer M, Van de Casteele T, Tomaka F. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naive patients in the ARTEMIS trial. HIV Med. 2013 Jan;14(1):49-59. doi: 10.1111/j.1468-1293.2012.01060.x. Epub 2012 Oct 23.
- Phase III randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r in treatment- naive HIV-1 infected patients.Link provided by the sponsor.
- Phase III randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r in treatment- naive HIV-1 infected patients.Link provided by the sponsor.
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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.
Tibotec Pharmaceuticals Clinical Trial study director
Tibotec Pharmaceutical Limited
89 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LPV/RTV and TMC-114/RTV in people with HIV, run by Tibotec Pharmaceuticals, Ireland at 89 sites in 25 countries.
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 5 inclusion and 5 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 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 89 sites in United States, Germany, Russia, France, Australia and 20 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48 (time frame: 48 weeks). 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 NCT00258557, which also lists 2 linked publications.
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 2013.