Clinical trial NCT00258557: 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: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: HIV
Anti-Retroviral agents
HIV-1
TMC114/r
Treatment naïve patients
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2005-11-24
Enrollment: 692
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.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).

Eligibility criteria: 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

Primary outcomes:
measure: Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment
timeFrame: 192 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Fort Lauderdale
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Safety Harbor
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Las Vegas
country: United States
state: Nevada
city: Brooklyn
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Mar Del Plata N/A
country: Argentina
city: Neuquen
country: Argentina
city: Brisbane
country: Australia
city: Darlinghurst
country: Australia
city: Surry Hills
country: Australia
city: Westmead N/A
country: Australia
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Providencia
country: Chile
city: Santiago
country: Chile
city: Costa Rica
country: Costa Rica
city: San Jose
country: Costa Rica
city: Aalborg
country: Denmark
city: Copenhagen Ø
country: Denmark
city: Hvidovre
country: Denmark
city: Bobigny
country: France
city: Lyon
country: France
city: Nice
country: France
city: Orleans Cedex 2
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
city: Mannheim
country: Germany
city: Munich
country: Germany
city: München
country: Germany
city: Athens
country: Greece
city: Guatemala
country: Guatemala
city: Sungai Buloh
country: Malaysia
city: Ciudad De Mexico
country: Mexico
city: Del Tlalpan
country: Mexico
city: Guadalajara N/A
country: Mexico
city: Mex Ctity
country: Mexico
city: Panama
country: Panama
city: San Juan
country: Puerto Rico
city: Kazan
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Sint Petersburg
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Singapore
country: Singapore
city: Cape Town
country: South Africa
city: Dundee
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Barcelona N/A
country: Spain
city: Barcelona
country: Spain
city: Zurich N/A
country: Switzerland
city: Taipei
country: Taiwan
city: Tiachung
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Brighton
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceutical Limited
name: Tibotec Pharmaceuticals Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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-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.