The Maraviroc Central Nervous System (CNS) Study

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: Maraviroc

• Registration Number: NCT00982878
• Lead Sponsor: Imperial College London

Brief Summary

The purpose of this study is to describe the Central Nervous System exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state.

Detailed Description

15 HIV-1 infected subjects currently receiving stable antiretroviral therapy will be recruited. At study entry, within 14 days of screening procedures, subjects will commence maraviroc dosed at 150 mg twice daily. For the rest of study period antiretroviral therapy will comprise:

* Truvada™ one tablet once daily at 0900

* Kaletra™ two tablets twice daily 0900 and 2100

* maraviroc 150 mg twice daily at 0900 and 2100

Subjects will attend for regular clinic visits during study treatment phase.

On day 15, subjects will attend the unit in the morning prior to usual dosing time. Blood with be drawn to assess plasma maraviroc concentration pre dose and pre lumbar puncture. A lumbar puncture will be performed under standard aseptic techniques to asses CSF maraviroc concentration and routine CSF parameters.

On completion of this study visit, subjects will cease maraviroc, continue on their usual antiretroviral regimen and attend for a follow up visit 10 days later.

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-22
• Study First Submitted QC: 2009-09-22
• Study First Posted: 2009-09-23
• Primary Completion: 2010-07
• Study Completion: 2011-02
• Results First Submitted: 2019-09-23
• Status Verified: 2019-10
• Results First Submitted QC: 2019-10-15
• Last Update Submitted: 2019-10-15
• Results First Posted: 2019-11-04
• Last Update Posted: 2019-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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 a stable antiretroviral regimen comprising of:

  • tenofovir 245 mg daily
  • emtricitabine 200 mg daily
  • a boosted protease inhibitor

• no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing

• Between 18 to 65 years of age, inclusive

• subjects in good health upon medical history, physical exam, and laboratory testing

• 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 through completion of the study including 30 days following last dose of study drug:

  • barrier contraceptives (condom, diaphragm with spermicide)
  • IUD PLUS a barrier contraceptive

• Female subjects of childbearing potential must have a negative 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 including 30 days following last dose of study drug.

• Have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen and no serologic evidence of hepatitis C virus infection by a HCV antibody or HCV PCR.

• Have screening laboratory results (haematology, chemistry, and urinalysis) 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

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Exclusion Criteria

• current alcohol abuse or drug dependence

• active opportunistic infection or significant co-morbidities including dementia

• current prohibited concomitant medication (as listed in section 4.1.4)

• Have a body mass index (BMI) > 32

• Contraindication to lumbar puncture examination. Such as:

  • Existing neurological diseases
  • Bleeding disorders

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Maraviroc	Maraviroc	-

Primary Outcome Measures

Name	Time	Method
CSF (Cerebrospinal Fluid) : Plasma Ratio of Maraviroc 1H Magnetic Resonance Spectroscopy (1H-MRS)	15 days	To describe the CNS exposure of maraviroc in HIV-1 infected subjects receiving a stable antiretroviral regimen, including maraviroc, at steady state.; It were assessed by in vivo cerebral (1)H magnetic resonance spectroscopy ((1)H-MRS).; Cerebral MRS imaging (T1- and T2-weighted images) was performed on a Phillips Achieva™ 1.5 Tesla magnetic resonance (MR) scanner (Phillips NV, Best, Netherlands) and studied by an experienced neuroradiologist

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	15 days	To evaluate the short term safety and tolerability of maraviroc in HIV-1 infected subjects on stable antiretroviral therapy

Trial Locations

Locations (1)

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom