The Maraviroc Darunavir/Ritonavir Once Daily Pharmacokinetic Study

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01348763
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 7
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: Maraviroc; Drug: Truvada; Drug: Darunavir	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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 Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Truvada, Darunavir/r and Maraviroc Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada	Drug: Maraviroc; Maraviroc 150 mg daily; Drug: Truvada; daily until 10. day then stop; Drug: Darunavir; daily until 10. day then stop

Outcome Measures

Primary Outcome Measures

1. The Ratio of the Maximum Plasma Concentration of Maraviroc Between 20 and 10 Day [10 day, 20 days]

   On day 10 of the study the maximum concentractions of maraviroc will be measured . On day 20 of the study the maximum plasma concentractions maraviroc will be measured .

Secondary Outcome Measures

1. Number of Participants With Changes in Haematology and Biochemistry Laboratory Tests [35 days]

   Haematology and biochemistry laboratory tests such as full blood count, elelectrolytes and lipids will be measured to assess for changes.

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 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

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

Investigators

• Principal Investigator: Alan Winston, MB BH, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT01348763
• Other Study ID Numbers: MRV_DRV_PK; 2009-014924-42
• First Posted: May 5, 2011
• Last Update Posted: Oct 31, 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 Imperial College London: HIV
• Additional relevant MeSH terms: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Maraviroc; Darunavir

Study Results

Participant Flow

Arm/Group Title	Truvada, Darunavir/r and Maraviroc
Arm/Group Description	Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada Maraviroc: Maraviroc 150 mg daily
Period Title: With Tenofovir/Emtricitabine (10 Days)
STARTED	13
COMPLETED	11
NOT COMPLETED	2
Period Title: With Tenofovir/Emtricitabine (10 Days)
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Truvada, Darunavir/r and Maraviroc
Arm/Group Description	Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada Maraviroc: Maraviroc 150 mg daily
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (8.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
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	3 27.3%
White	8 72.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	11 100%

Outcome Measures

1. Primary Outcome

Title	The Ratio of the Maximum Plasma Concentration of Maraviroc Between 20 and 10 Day
Description	On day 10 of the study the maximum concentractions of maraviroc will be measured . On day 20 of the study the maximum plasma concentractions maraviroc will be measured .
Time Frame	10 day, 20 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Truvada, Darunavir/r and Maraviroc
Arm/Group Description	Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada Maraviroc: Maraviroc 150 mg daily
Measure Participants	11
Mean (95% Confidence Interval) [ratio]	0.99

2. Secondary Outcome

Title	Number of Participants With Changes in Haematology and Biochemistry Laboratory Tests
Description	Haematology and biochemistry laboratory tests such as full blood count, elelectrolytes and lipids will be measured to assess for changes.
Time Frame	35 days

Outcome Measure Data

Analysis Population Description

No data reported

Arm/Group Title	Truvada, Darunavir/r and Maraviroc
Arm/Group Description	Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada Maraviroc: Maraviroc 150 mg daily
Measure Participants	11
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	1 year
Arm/Group Title	Truvada, Darunavir/r and Maraviroc
Arm/Group Description	Participants will be taking Truvada, Darunavir/r before entering the study. On day 1 they will add maraviroc then on day 11 they will stop the Truvada Maraviroc: Maraviroc 150 mg daily
All Cause Mortality
	Truvada, Darunavir/r and Maraviroc
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Truvada, Darunavir/r and Maraviroc
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Truvada, Darunavir/r and Maraviroc
	Affected / at Risk (%)	# Events
Total	0/11 (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.