Clinical trial NCT00524368: A Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN)
Official title: A Randomized, Open-label Trial to Compare the Efficacy, Safety and Tolerability of DRV/Rtv (800mg/100mg) q.d Versus DRV/Rtv (600mg/100mg) b.i.d in Early Treatment-experienced HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus - Type 1
Keywords: Human immunodeficiency virus - type 1
HIV-1 Infection
TMC-114
Darunavir
Ritonavir
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2007-09-03
Enrollment: 590
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 test if being treated with darunavir/ritonavir (DRV/rtv) 800/100 mg daily is as effective as being treated with DRV/rtv 600/100 mg twice daily, in early antiretroviral (ARV)-experienced patients when given along with selected optimized background regimen (OBR).

Detailed description: This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention) study in which 590 patients will be randomly assigned to receive either DRV/rtv 800/100 mg daily or DRV/rtv 600/100 mg twice daily along with the selected OBR. An OBR will consist of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) selected by the investigator. The study will include a 4 week screening period, 48-weeks of treatment period and 4-weeks of follow-up. The study will also consists of extension phase after Week 48: in regions where DRV is not yet commercially available or reimbursed by the health care system, patients who complete the 48 weeks of treatment with DRV/rtv and who continue to benefit from this treatment, will have the opportunity to continue DRV treatment as a 600 mg twice daily dosage until DRV is reimbursed and available via the public and/or private health care system or until its development is discontinued. Safety evaluation will consists of adverse events (including specific toxicities), clinical laboratory tests, vital signs, electrocardiogram, physical and skin examination.

Eligibility criteria: Inclusion Criteria:

* Patients with documented human immunodeficiency virus - Type 1 (HIV-1) infection
* Patients with a viral load greater than 1,000 HIV-1 ribonucleic acid (RNA) copies/mL
* Stable highly active antiretroviral therapy (HAART) regimen for at least 12 weeks at screening
* In the investigator's opinion, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not a valid treatment option, because of the patient's antiretroviral (ARV) treatment history, ARV resistance testing, medication-taking behavior, safety and tolerability concerns, or other patient-related factors
* Prescreening or/and screening plasma HIV-1 RNA greater than 1,000 copies/mL on HAART regimen at screening

Exclusion Criteria:

* Presence of any currently active conditions that fit the definition of the World Health Organization (WHO) Clinical Stage 4, with the following exceptions: stable cutaneous kaposi's sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study time period, wasting syndrome
* Patients for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine
* Previous or current use of enfuvirtide (ENF), tipranavir and/or DRV
* Life expectancy of less than 12 months
* Pregnant or breast-feeding females
* Any active clinically significant disease (eg, tuberculosis \[TB\], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study

Primary outcomes:
measure: Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
timeFrame: 48 Weeks
Secondary outcomes:
measure: Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL)
timeFrame: 48 weeks
measure: Change in log10 Viral Load From Baseline at Week 48
timeFrame: 48 weeks
measure: Time to Reach First Virologic Response
timeFrame: 48 weeks
measure: Time to Loss of Virologic Response
timeFrame: 48 weeks
measure: Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks
timeFrame: 48 weeks
measure: Change in CD4+ Cell Count From Baseline
timeFrame: 48 Weeks
measure: Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
timeFrame: 48 weeks
measure: Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48
timeFrame: 48 weeks
measure: Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv
timeFrame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48.
measure: Predose Plasma Concentration (C0h) of DRV and Rtv.
timeFrame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48
measure: Number of Participants Developing Mutations at Endpoint
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Oakland
country: United States
state: California
city: Palm Springs
country: United States
state: California
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Laudersale
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: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Massachusetts
city: Berkley
country: United States
state: Michigan
city: Newark
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Huntersville
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Harlingen
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Guernica
country: Argentina
city: Neuquen
country: Argentina
city: Rosario
country: Argentina
city: Darlinghurst
country: Australia
city: Surry Hills
country: Australia
city: Wien
country: Austria
city: Curitiba
country: Brazil
city: Distrito Barao Geraldo-Campina
country: Brazil
city: Pinheiros
country: Brazil
city: Recife
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Providencia
country: Chile
city: Santiago
country: Chile
city: Lyon
country: France
city: Nice
country: France
city: Orleans Cedex 2
country: France
city: Paris Cedex 10
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Guatemala
country: Guatemala
city: Budapest
country: Hungary
city: Ipoh
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Pulau Pinang
country: Malaysia
city: Sungai Buloh
country: Malaysia
city: Panama
country: Panama
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Constanta
country: Romania
city: Iasi
country: Romania
city: Timisoara
country: Romania
city: Cape Town
country: South Africa
city: Cyrildene Johannesburg Gauteng
country: South Africa
city: Dundee
country: South Africa
city: Durban
country: South Africa
city: Houghton, Johannesburg
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Westdene Johannesburg Gauteng
country: South Africa
city: Barcelona N/A
country: Spain
city: Madrid
country: Spain
city: Kaohsiung County
country: Taiwan
city: Taichung 407
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Nonthaburi
country: Thailand
city: London
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Lathouwers E, De La Rosa G, Van de Casteele T, Baeten B, Tomaka F, De Meyer S, Picchio G. Virological analysis of once-daily and twice-daily darunavir/ritonavir in the ODIN trial of treatment-experienced patients. Antivir Ther. 2013;18(3):289-300. doi: 10.3851/IMP2569. Epub 2013 Apr 4.