Trial Outcomes & Findings for Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS) (NCT NCT01276236)
NCT ID: NCT01276236
Last Updated: 2021-03-05
Results Overview
To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.
COMPLETED
PHASE2
13 participants
Up to 96 weeks
2021-03-05
Participant Flow
Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines.
Participant milestones
| Measure |
Treatment Arm (Maraviroc)
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Overall Study
STARTED
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13
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Overall Study
Week 36 Visit
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13
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Overall Study
Week 56 Visit
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9
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Overall Study
Week 76 Visit
|
8
|
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Overall Study
COMPLETED
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7
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Overall Study
NOT COMPLETED
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6
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Reasons for withdrawal
| Measure |
Treatment Arm (Maraviroc)
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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Overall Study
Lack of Efficacy
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2
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Overall Study
Withdrawal by Subject
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4
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Baseline Characteristics
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
Baseline characteristics by cohort
| Measure |
Treatment Arm (Maraviroc)
n=13 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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Age, Continuous
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51.5 years
STANDARD_DEVIATION 3.0 • n=93 Participants
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Sex: Female, Male
Female
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0 Participants
n=93 Participants
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Sex: Female, Male
Male
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13 Participants
n=93 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=93 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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13 Participants
n=93 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=93 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=93 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=93 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=93 Participants
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Race (NIH/OMB)
White
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13 Participants
n=93 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=93 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=93 Participants
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Region of Enrollment
United States
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13 participants
n=93 Participants
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Mean duration of Human Immunodeficiency Virus (HIV) diagnosis
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18.3 years
STANDARD_DEVIATION 2.5 • n=93 Participants
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Mean duration of Kaposi's Sarcoma (KS) diagnosis
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7.5 years
STANDARD_DEVIATION 2.4 • n=93 Participants
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Mean cluster of differentiation 4 (CD4) count
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578.3 cells in a cubic millimetre (cells/mm3)
STANDARD_DEVIATION 86.3 • n=93 Participants
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Number of Kaposi's Sarcoma (KS) Lesions at Baseline
>50 lesions
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4 Participants
n=93 Participants
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Number of Kaposi's Sarcoma (KS) Lesions at Baseline
<=50 lesions
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9 Participants
n=93 Participants
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PRIMARY outcome
Timeframe: Up to 96 weeksTo assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=13 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area
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11 Participants
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PRIMARY outcome
Timeframe: Up to 96 weeksUp to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96.
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=13 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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Percent Change in KS Total Surface Area
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-28.1 percentage change
Standard Deviation 7.9
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PRIMARY outcome
Timeframe: Up to 96 weeksPopulation: Only seven patients total had measurable edema at any time during the study
The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema.
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=7 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Change in Edema Grade
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-0.7 scores on a scale
Standard Deviation 0.3
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SECONDARY outcome
Timeframe: Up to 96 weeksPopulation: Data was not collected for this endpoint
Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 96 weeksPopulation: Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.
Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=5 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Percent Change in CCR5 Levels on CD4+ T-Cells
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22.8 percentage change
Standard Deviation 5.9
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SECONDARY outcome
Timeframe: Up to 96 weeksPopulation: Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.
Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=5 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Percent Change in CCR5 Levels on CD8+ T-cells
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21.6 percentage change
Standard Deviation 3.5
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SECONDARY outcome
Timeframe: Up to 96 weeksPopulation: Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.
Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=5 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells
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89.7 percentage change
Standard Deviation 48.2
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SECONDARY outcome
Timeframe: Up to 96 weeksPopulation: Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.
Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells
Outcome measures
| Measure |
Treatment Arm (Maraviroc)
n=5 Participants
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells
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50.5 percentage change
Standard Deviation 35.9
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Adverse Events
Treatment Arm (Maraviroc)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Arm (Maraviroc)
n=13 participants at risk
The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.
Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.
Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.
Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.
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|---|---|
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General disorders
Fatigue
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30.8%
4/13 • Number of events 4 • Up to 96 weeks
No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.
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Respiratory, thoracic and mediastinal disorders
Cough
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23.1%
3/13 • Number of events 3 • Up to 96 weeks
No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.
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Nervous system disorders
Headache
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15.4%
2/13 • Number of events 2 • Up to 96 weeks
No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.
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Gastrointestinal disorders
Diarrhea
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15.4%
2/13 • Number of events 2 • Up to 96 weeks
No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.
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Gastrointestinal disorders
Nausea
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7.7%
1/13 • Number of events 1 • Up to 96 weeks
No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.
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Additional Information
Dr. Toby Maurer, MD
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place