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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00524368
First received: August 30, 2007
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

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).


Condition Intervention Phase
Human Immunodeficiency Virus - Type 1
Drug: Darunavir (DRV)
Drug: Ritonavir (rtv)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • 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 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.


Secondary Outcome Measures:
  • Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Number of participants with confirmed plasma viral load less than 400 copies/mL at Week 48.

  • Change in log10 Viral Load From Baseline at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Time to Reach First Virologic Response [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Time (in weeks) to achieve viral load less than 50 copies/mL by the participants.

  • Time to Loss of Virologic Response [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Time taken to lose the virologic response ie, plasma viral load less than 50 copies/mL by participants.

  • Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Change in CD4+ Cell Count From Baseline [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    CD4+ cell count was calculated using the Last Observation Carried Forward (LOCF) algorithm.

  • Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    The FAHI is a 44-item questionnaire and incorporates 5 functional scales (physical well-being, emotional well-being/living with HIV, functional and global well-being, social well-being, and cognitive functioning). Each scale included several questions (all 5 scales include total 44 questions). For each question, participants gave a score of either 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). Total FAHI imputed score is calculated by adding scores for each question. The range of total FAHI score is 0 to 176. Higher scores indicate worsening.

  • Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Self-reported adherence to the ARV medications was measured. The M-MASRI asks participants to report the number of doses taken, as well as the number of doses taken during the last 30 days prior to the study visit by means of a horizontal visual analogue scale (VAS) that generates a self-rated percentage of doses of all the ARV medications taken during the past 30 days.

  • Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter AUC24h was assessed from the time of study medication administration upto 24 hour postdose. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.

  • Predose Plasma Concentration (C0h) of DRV and Rtv. [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter C0h was assessed. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.

  • Number of Participants Developing Mutations at Endpoint [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Development of Mutations in Virologic Failures (Plasma Viral Load less than 50 Copies/mL) at endpoint.


Enrollment: 590
Study Start Date: October 2007
Study Completion Date: October 2011
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DRV/rtv 800/100 mg once daily
Two 400 mg darunavir (DRV) ie, TMC114 tablets + one 100 mg ritonavir (rtv) capsule once daily.
Drug: Darunavir (DRV)
DRV/rtv 800/100 mg once daily group: 2 tablets of 400 mg of DRV administered orally once daily. DRV/rtv 600/100 mg twice daily group: 1 tablet of 600 mg DRV administered orally twice daily.
Other Name: TMC114
Drug: Ritonavir (rtv)
DRV/rtv 800/100 mg once daily group: One capsule of 100 mg of ritonavir administered orally once daily. DRV/rtv 600/100 mg twice daily group: One capsule of 100 mg of ritonavir administered orally twice daily.
Other Name: rtv
Experimental: DRV/rtv 600/100 mg twice daily
One 600 mg TMC114 tablet + one 100 mg capsule of rtv twice daily.
Drug: Darunavir (DRV)
DRV/rtv 800/100 mg once daily group: 2 tablets of 400 mg of DRV administered orally once daily. DRV/rtv 600/100 mg twice daily group: 1 tablet of 600 mg DRV administered orally twice daily.
Other Name: TMC114
Drug: Ritonavir (rtv)
DRV/rtv 800/100 mg once daily group: One capsule of 100 mg of ritonavir administered orally once daily. DRV/rtv 600/100 mg twice daily group: One capsule of 100 mg of ritonavir administered orally twice daily.
Other Name: rtv

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00524368

  Show 87 Study Locations
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

No publications provided by Tibotec Pharmaceuticals, Ireland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00524368     History of Changes
Obsolete Identifiers: NCT00613990
Other Study ID Numbers: CR013783, TMC114-TiDP31-C229, 2007-001939-61
Study First Received: August 30, 2007
Results First Received: August 27, 2010
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration
Great Britain: Research Ethics Committee

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Human immunodeficiency virus - type 1
HIV-1 Infection
TMC-114
Darunavir
Ritonavir

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014