DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
Gregory Huhn, Ruth M. Rothstein CORE Center
ClinicalTrials.gov Identifier:
NCT01423812
First received: August 24, 2011
Last updated: July 16, 2013
Last verified: July 2013
  Purpose

Darunavir is a nonpeptidic protease inhibitor with a high genetic barrier to resistance that evolved from a prototype compound synthesized using structure-based design strategies. Once-daily darunavir at 800mg boosted with 100mg of ritonavir is an effective antiretroviral agent indicated for HIV-infected treatment-naïve patients. In treatment-experienced patients, darunavir was initially approved for twice-daily administration boosted with twice-daily ritonavir at 600mg and 100mg, respectively. Recently, once-daily darunavir/ritonavir was approved for use in treatment-experienced adult patients with viremia with no darunavir resistance mutations. In treatment-experienced patients with viral suppression, switching from an antiretroviral taken twice-daily to a once-daily dose is an attractive option to promote greater patient acceptability and adherence, and potentially minimize side effects and toxicities. Because of darunavir/ritonavir's high genetic barrier to resistance and well-established safety profile at a once-daily dose, switching patients with virologic suppression from twice-daily darunavir/ritonavir to once-daily darunavir/ritonavir will likely confer attributes more favorable to patients through a simplified dosing schedule and lower potential for lipid elevation without the loss of virologic control. DRIVESHAFT is a 48-week Phase 4, randomized, open label, comparative study. The study will be conducted in 60 HIV-1 infected, antiretroviral experienced, virologically-suppressed patients on regimens containing darunavir 600mg/ ritonavir 100mg twice-daily and a minimum of two other antiretrovirals, with a history of 0-1 darunavir-associated resistance mutations. Subjects will be randomized 1:1 to switch to darunavir 800mg/ ritonavir 100mg once-daily or continue on their current regimen. Rates of virologic suppression of once-daily darunavir/ritonavir regimens relative to darunavir/ritonavir twice-daily regimens will be compared, and safety, change from baseline fasting lipid parameters, and adherence will be evaluated.


Condition Intervention Phase
HIV
Drug: Twice-daily Darunavir/ritonavir
Drug: Once-daily Darunavir/ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DRIVESHAFT : Darunavir/Ritonavir In Virologically-suppressed Experienced Subjects Halving an Antiretroviral by Finetuning Therapy - A Phase IV Randomized, Open-Label Study to Evaluate in HIV-1 Infected , Virologically-suppressed Patients on Regimens With Darunavir 600mg/ Ritonavir 100mg Twice-daily Switching to Darunavir 800mg/ Ritonavir 100mg Once-daily Versus Continuing Darunavir 600mg/ Ritonavir 100mg Twice-daily Containing Regimens

Resource links provided by NLM:


Further study details as provided by Ruth M. Rothstein CORE Center:

Primary Outcome Measures:
  • Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects [ Time Frame: 48 weeks after randomization to study medication ] [ Designated as safety issue: No ]
    Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using a Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA's "snapshot" algorithm


Secondary Outcome Measures:
  • Secondary Efficacy Endpoints [ Time Frame: Within 48 weeks after randomization to study medication ] [ Designated as safety issue: Yes ]
    • Proportion of subjects with plasma HIV-1 RNA <50 c/mL and <400 c/mL at Week 24
    • Proportion of subjects with plasma HIV-1 RNA <400 c/mL at Week 48

  • Safety Assessment [ Time Frame: Within 48 weeks of randomization to study medications ] [ Designated as safety issue: Yes ]
    •Compare the tolerability, safety, and change in lipid parameters(total cholesterol, LDL, HDL, triglycerides) of once-daily versus twice-daily darunavir/ritonavir containing regimens over 48 weeks

  • Immunologic Endpoints [ Time Frame: 48 weeks after randomization to study medications ] [ Designated as safety issue: No ]
    •Absolute values and changes from baseline in CD4+ and CD8+ over time

  • Assessment of Virologic Failure [ Time Frame: Within 48 weeks of randomization to study medications ] [ Designated as safety issue: No ]
    •Assess the development of viral resistance in subjects experiencing virological failure

  • Medication Adherence Assessment [ Time Frame: Within 48 weeks of randomization to study medications ] [ Designated as safety issue: No ]
    Characterize adherence to once-daily versus twice-daily darunavir/ritonavir containing regimens using the Modified Medication Adherence Self-Report Inventory (M-MASRI) scale


Estimated Enrollment: 60
Study Start Date: January 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Once-daily Darunavir/ritonavir
Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily
Drug: Once-daily Darunavir/ritonavir
Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks
Active Comparator: Twice-daily Darunavir/ritonavir
Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily
Drug: Twice-daily Darunavir/ritonavir
Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ART-experienced, HIV-1 infected subjects ≥18 years of age.
  2. A female subject is eligible to enter and participate in the study if she:

    1. is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or,
    2. is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy:

      • Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications.
      • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide).
      • Approved hormonal contraception may be administered with darunavir/ritonavir
      • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year
      • Any other method with published data showing that the expected failure rate is <1% per year.

    Any contraception method must be used consistently and in accordance with the approved product label. All subjects participating in the study should be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom/spermicide).

  3. CD4 >50 cells/mm3
  4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen
  5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals
  6. Negative serum pregnancy test at screening visit

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

  1. Known hypersensitivity reaction to agents being utilized in the study
  2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype
  3. Pregnant or breast feeding woman
  4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01423812

Locations
United States, Illinois
Ruth M. Rothstein CORE Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Ruth M. Rothstein CORE Center
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
  More Information

No publications provided

Responsible Party: Gregory Huhn, Attending Physician, Ruth M. Rothstein CORE Center
ClinicalTrials.gov Identifier: NCT01423812     History of Changes
Other Study ID Numbers: TMC114HIV4063
Study First Received: August 24, 2011
Last Updated: July 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ruth M. Rothstein CORE Center:
HIV
treatment-experienced
protease inhibitor
adherence
lipids

Additional relevant MeSH terms:
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 April 22, 2014