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.

Tracking Information
First Submitted Date ICMJE	November 22, 2005
First Posted Date ICMJE	November 24, 2005
Last Update Posted Date	June 26, 2013
Study Start Date ICMJE	September 2005
Actual Primary Completion Date	June 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 19, 2007)	Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48 [ Time Frame: 48 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: November 22, 2005)	Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48
Change History	Complete list of historical versions of study NCT00258557 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 19, 2007)	Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment [ Time Frame: 192 weeks ]
Original Secondary Outcome Measures ICMJE; (submitted: November 22, 2005)	Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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.
Official Title ICMJE	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.
Brief 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).
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 Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV
Intervention ICMJE	Drug: LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks; Drug: TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks
Study Arms	Experimental: 002 TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks Intervention: Drug: TMC-114/RTV; Active Comparator: 001 LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks Intervention: Drug: LPV/RTV
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.; Orkin 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-naïve 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 2, 2009)	692
Original Enrollment ICMJE; (submitted: November 22, 2005)	660
Actual Study Completion Date	May 2012
Actual Primary Completion Date	June 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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. Exclusion Criteria: 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belgium, Canada, Chile, Costa Rica, Denmark, France, Germany, Greece, Guatemala, Malaysia, Mexico, Panama, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Removed Location Countries	Brazil, Hungary, Italy, Netherlands, Peru, Poland, Portugal, Uganda, Venezuela
Administrative Information
NCT Number ICMJE	NCT00258557
Other Study ID Numbers ICMJE	CR002800; TMC114-C211 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Tibotec Pharmaceuticals, Ireland
Study Sponsor ICMJE	Tibotec Pharmaceuticals, Ireland
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
PRS Account	Tibotec Pharmaceuticals, Ireland
Verification Date	June 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP