The Maraviroc Central Nervous System (CNS) Study

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00982878
• Collaborator: Pfizer (Industry)
• Enrollment: 13
• Location: 1
• Arm: 1
• Actual Duration (Months): 17
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Maraviroc	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Penetration of Maraviroc Into the Central Nervous System in HIV-1 Infected Subjects on Stable Antiretroviral Therapy; a Phase I Pharmacokinetic Study
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maraviroc	Drug: Maraviroc; 150mg twice daily

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College Healthcare NHS Trust	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Imperial College London
• Pfizer

Investigators

• Principal Investigator: Alan Winston, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alan Winston, Reader and Honorary HIV consultant, Imperial College London
• ClinicalTrials.gov Identifier: NCT00982878
• Other Study ID Numbers: 2008-008437-10
• First Posted: Sep 23, 2009
• Last Update Posted: Nov 4, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alan Winston, Reader and Honorary HIV consultant, Imperial College London: treatment experienced
• Additional relevant MeSH terms: HIV Infections; Maraviroc

Study Results

Participant Flow

Arm/Group Title	Maraviroc
Arm/Group Description	Maraviroc: 150mg twice daily
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Maraviroc
Arm/Group Description	Maraviroc: 150mg twice daily
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (7.9)
Sex: Female, Male (Count of Participants)
Female	3 25%
Male	9 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 58.3%
White	4 33.3%
More than one race	1 8.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	12 100%
Years since HIV diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11 (4.6)
Baseline CD4 cell count (cells/ul) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/ul]	503 (199)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28 (3.5)

Outcome Measures

1. Primary Outcome

Title	CSF (Cerebrospinal Fluid) : Plasma Ratio of Maraviroc 1H Magnetic Resonance Spectroscopy (1H-MRS)
Description	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
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	Maraviroc: 150mg twice daily
Measure Participants	12
Mean (Full Range) [ratio]	1.01

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	Maraviroc: 150mg twice daily
Measure Participants	12
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	15 days
Arm/Group Title	Maraviroc
Arm/Group Description	Maraviroc: 150mg twice daily
All Cause Mortality
	Maraviroc
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.