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

Condition(s) targeted: HIV

Intervention: Twice-daily Darunavir/ritonavir (Drug); Once-daily Darunavir/ritonavir (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Ruth M. Rothstein CORE Center

Overall contact:
Andrew Sigman, Phone: 312-572-4542, Email: asigman@cookcountyhhs.org

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects

Secondary outcome:

Secondary Efficacy Endpoints

Safety Assessment

Immunologic Endpoints

Assessment of Virologic Failure

Medication Adherence Assessment

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Andrew Sigman, Phone: 312-572-4542, Email: asigman@cookcountyhhs.org

Ruth M. Rothstein CORE Center, Chicago, Illinois 60612, United States; Recruiting
Andrew Sigman, Phone: 312-572-4559, Email: asigman@cookcountyhhs.org
Gregory D Huhn, MD, MPHTM, Principal Investigator

Starting date: January 2012
Last updated: July 31, 2012