DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects (DRIVESHAFT)
This study has been completed.
Sponsor:
Ruth M. Rothstein CORE Center
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: April 20, 2015
Last verified: April 2015
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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
| Enrollment: | 60 |
| Study Start Date: | January 2012 |
| Study Completion Date: | April 2015 |
| Primary Completion Date: | May 2014 (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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- ART-experienced, HIV-1 infected subjects ≥18 years of age.
-
A female subject is eligible to enter and participate in the study if she:
- 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,
-
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).
- CD4 >50 cells/mm3
- HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen
- Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals
- Negative serum pregnancy test at screening visit
Exclusion Criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
- Known hypersensitivity reaction to agents being utilized in the study
- >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
- Pregnant or breast feeding woman
- Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis
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: NCT01423812
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
Additional Information:
Publications:
1. De Meyer S, et al. Antiviral activity of TMC 114, a potent next generation protease inhibitor against more than 4000 recent recombinant clinical isolates exhibiting a wide range of protease inhibitor resistance profile. Antiviral Ther 2003;8:3S19. 2. De Meyer S, et al. In vitro selection experiments demonstrate an increased genetic barrier to resistance development to TMC 114 as compared with currently licensed protease inhibitors. Antiviral Ther 2002;7(Suppl 1):S5. 3. De Meyer SD, et al. Phenotypic and genotypic determinants of resistance to TMC 114: pooled analysis of POWER 1,2, and 3. Antiviral Ther 2006;11:S83. 4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December 1,2009;1-161. Available at http://www.aidsinfo.nih.gov/ContentFiles/Adultand AdolescentGL.pdf. Accessed September 15, 2010. 5. Clotet B, et al. Efficacy and Safety of Darunavir/ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: A Pooled Subgroup Analysis of Data from Two Randomized Trials. The Lancet 2007;369:1169-78. 6. Cahn PK, et al. Efficacy and Safety at 48 Weeks of Once-daily vs Twice-daily DRV.r in Treatment-experienced HIV-1-positive Patients with No DRV Resistance-associated Mutations: The ODIN Trial. Abstract 57. 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. 7. Moltó J, et al. Treatment simplification to once daily darunavir/ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients. Antivir Ther. 2010;15(2):219-25. 8. Paterson DL, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133:21-30.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | April 20, 2015 |
| 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 |
Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |
ClinicalTrials.gov processed this record on September 28, 2016