Clinical trial NCT01348763: The Maraviroc Darunavir/Ritonavir Once Daily Pharmacokinetic Study
Official title: A Phase 1 Pharmacokinetic Study to Assess the Steady State Pharmacokinetic Profile and Short Term Safety of Maraviroc Dosed With Darunavir/Ritonavir All Once Daily, With and Without Nucleoside Analogues, in HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Keywords: HIV
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2011-05-05
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This is a phase I, open label, prospective, two phase pharmacokinetic study. Subjects currently attending for HIV care at St. Mary's Hospital, London will be eligible.

Detailed description: The study will describe the steady state pharmacokinetic parameters and short term safety of maraviroc/darunavir/ritonavir dosed at 150/800/100 mg once daily with and without tenofovir/emtricitabine 245/200 mg once daily in HIV-1 infected subjects.

Fifteen HIV-1 infected subjects will be recruited. Eligible subjects will currently be receiving antiretroviral therapy comprising:

* tenofovir/emtricitabine 245/200 mg daily plus
* darunavir/ritonavir 800/100 mg daily

On day 1, subjects will modify their current antiretroviral therapy to the following:

* tenofovir/emtricitabine 245/200 mg daily plus
* darunavir/ritonavir 800/100 mg daily plus
* maraviroc 150 mg daily On day 10 subjects will undergo an intensive pharmacokinetic visit.

On day 11, subjects will modify their current antiretroviral therapy to the following:

* darunavir/ritonavir 800/100 mg daily plus
* maraviroc 150 mg daily (i.e. tenofovir/emtricitabine will be discontinued) On day 20 subjects will undergo an intensive pharmacokinetic visit. Following completion of this study phase, subjects will recommence their usual antiretroviral treatment regimen and attend for a study follow up visit.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected males or females
* signed informed consent
* plasma HIV RNA \< 50 copies/mL at screening and on at least one other occasion over the last 3 months
* currently receiving an antiretroviral regimen comprising of: tenofovir 245 mg daily,emtricitabine 200 mg daily, darunavir 800 mg daily and ritonavir 100 mg daily
* no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing if an HIV resistance test available
* Between 18 to 65 years of age, inclusive
* subjects in good health upon medical history, physical exam, and laboratory testing
* BMI above or equal to 18 and below 32
* Female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening until 8 weeks after completion of the study:
* barrier contraceptives (condom OR diaphragm PLUS spermicide) or oral, implant or injectable hormonal contraceptive PLUS a barrier contraceptive or
* IUD /IUS PLUS a barrier contraceptive
* Female subjects of childbearing potential must have a negative urine pregnancy test.
* Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study.
* Have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen and no serologic evidence of hepatitis C virus infection evidenced by a negative HCV antibody at screening.
* Have screening laboratory results (haematology and chemistry that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance
* CCR5 tropic HIV virus based on a genotypic tropism assay from either a stored plasma sample where available or fresh plasma

Exclusion Criteria:

* current alcohol abuse or drug dependence
* positive urine drug of abuse screening
* pregnancy
* active opportunistic infection or significant co-morbidities
* current disallowed concomitant medication

Primary outcomes:
measure: The Ratio of the Maximum Plasma Concentration of Maraviroc Between 20 and 10 Day
timeFrame: 10 day, 20 days
Secondary outcomes:
measure: Number of Participants With Changes in Haematology and Biochemistry Laboratory Tests
timeFrame: 35 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Alan Winston, MB BH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mora-Peris B, Croucher A, Else LJ, Vera JH, Khoo S, Scullard G, Back D, Winston A. Pharmacokinetic profile and safety of 150 mg of maraviroc dosed with 800/100 mg of darunavir/ritonavir all once daily, with and without nucleoside analogues, in HIV-infected subjects. J Antimicrob Chemother. 2013 Jun;68(6):1348-53. doi: 10.1093/jac/dkt006. Epub 2013 Jan 30.