Human Immunodeficiency Virus 1
Conditions
Keywords
Human immunodeficiency virus 1, Acquired immunodeficiency syndrome, Immunologic deficiency syndrome, Darunavir/ritonavir, Darunavir, Ritonavir, Nucleoside reverse transcriptase inhibitors (NRTIs), Prezista
Brief summary
The purpose of this study is to compare change of brachial artery flow mediated vasodilatation using Darunavir/Ritonavir (DRV/r) 800/100 mg once daily as a monotherapy (use of a single medication) versus a triple combination therapy containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) and DRV/r in Human immunodeficiency virus-1 (HIV-1) infected participants.
Detailed description
This is a Phase II, randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), controlled, single centre study. The study consists of 3 phases including, the screening phase (4 weeks before administration of study medication), treatment phase (48 weeks), and the follow-up phase (4 weeks). In the treatment phase, HIV-infected participants who have not changed their first-line treatment of highly active antiretroviral therapy (HAART) for at least 8 weeks and have documented evidence of their HIV- ribonucleic acid (RNA) measurements being virologically suppressed (HIV-RNA less than 50 copies/mL) for at least 24 weeks prior to the screening, will be randomly assigned equally in two treatment arms: triple combination therapy arm (DRV/r 800/100 mg once daily plus 2 NRTIs) or monotherapy arm (DRV/r 800/100 mg once daily). Participants in the triple combination arm who are already on 2 NRTIs prior to randomization may remain on these or switch them at baseline, where the participants on the monotherapy arm will discontinue HAART at baseline and will start DRV/r 800/100 mg once daily. Safety evaluations will include assessment of adverse events, significant vital signs, and significant laboratory tests. The total duration of the study will be 56 weeks.
Interventions
DRUGDarunavir(DRV)
Oral administration of tablet DRV 800 mg (2 tablets of 400 mg) once daily at the same time, within 30 minutes after food for 48 weeks
DRUGRitonavir
Oral administration of tablet ritonavir 100 mg once daily at the same time, within 30 minutes after food for 48 weeks
DRUG2 nucleoside reverse transcriptase inhibitors (NRTIs)
2 NRTIs will be administered as per the package inserts.
Sponsors
Janssen-Cilag S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Human immunodeficiency virus-1 (HIV-1) infected participants on their first-line treatment with highly active antiretroviral therapy (HAART) (combination of 2 or 3 nucleoside reverse transcriptase inhibitors \[NRTIs\] with at least 1 additional antiretroviral \[ARV\] from the non-nucleoside reverse transcriptase inhibitor \[NNRTI\] and/or protease inhibitors \[PI\] class) for at least 24 weeks, provided the same ARV combination for at least 8 weeks before screening * Participants' preference for a more convenient regimen and/or any current or history of toxicity on actual regimen * Plasma HIV-1 ribonucleic acid (RNA) less than 50 cp/ml for at least 24 weeks before screening, where single viral blips of more than 50 copies/mL are allowed * Cluster of differentiation 4 (CD4) count more than 100/mm3 at the start of HAART and more than 200/mm3 at screening * Healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram performed at screening * Agrees to protocol-defined use of effective contraception * Postmenopausal, surgically sterile, or abstinent female participants
Exclusion criteria
* History of coronary heart disease, uncontrolled hypertension, peripheral vascular disease and or cerebrovascular disease * History of virological failure on highly active antiretroviral therapy, plasma HIV-1 ribonucleic acid more than 500 copies/mL after initial full virological suppression while on ARV therapy and any PI mutations * Participants with significantly hepatic and liver insufficiency or diagnosed with acute viral hepatitis or have active clinically significant diseases and acquired immune deficiency syndrome (AIDS) defining illness at screening * Current significant tobacco use, active drug or alcohol use or dependence * Use of lipid-lowering drugs within 4 weeks prior to study entry and use of testosterone, anabolic steroids, oral contraceptives or hormonal replacement within 12 weeks prior to study entry or previous or current use of darunavir * Use of systemic glucocorticoids, long-acting inhaled steroids (inhaled via mouth or nose), or other immunomodulators within 30 days prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%) | Baseline (Day 1 of Week 1) to Week 24 | Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52) | — |
| Change From Baseline to Week 48 in Circulating Endothelial Cells | Baseline to Week 48 | — |
| Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells | Baseline to Week 48 | — |
| Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL | Baseline (Day1 of Week 1), Week 24, and Week 48 | — |
| Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL | Baseline, Week 24, and Week 48 | — |
| Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides | Baseline, Week 24, and Week 48 | — |
| Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline, Week 24, and Week 48 | The Homeostatic Model Assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. HOMA-IR is reflected in the diminished effect of insulin on hepatic glucose production. HOMA-IR is calculated as: (Glucose \[mg/dL\] X Insulin \[pmol/L\]) / (405 X 6.945). Higher scores indicate worse insulin resistance. |
| Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%) | Baseline to Week 48 | Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. |
| Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) | Baseline to Week 48 | Leg fat content will be analyzed by Dual Energy X-ray Absortiometry (DEXA scan). |
| Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT) | Baseline to Week 48 | Visceral fat content in abdomen will be analyzed with median change in VAT by an abdomen Computerized Tomography. |
| Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score | Baseline to Week 48 | T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density. |
| Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score | Baseline to Week 48 | Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density. |
| Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score | Baseline to Week 48 | T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density. |
| Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score | Baseline to Week 48 | Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density. |
| Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48 | Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52) | — |
| Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score | Baseline, Week 24, and Week 48 | The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of a participant. It is calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, and systolic blood pressure. The framingham risk score is calculated as: for males: 0 point (1 percentage) up to 17 points (30 percentages); whereas for females: 0 to 9 points (1 percentage) up to 25 points (30 percentage). Higher scores indicate high cardiovascular risk. |
Participant flow
Recruitment details
30 participants were enrolled at a single site in Italy.
Pre-assignment details
30 participants were randomly assigned to 2 treatment groups (15 participants in each group) and all participants received the study medication.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) administered once daily | 15 |
| Combination Therapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Monotherapy | Combination Therapy | Total |
|---|---|---|---|
| Age Continuous | 44.8 Years | 43.0 Years | 44.6 Years |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 15 | 11 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%)
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Time frame: Baseline (Day 1 of Week 1) to Week 24
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%) | -4.8 Percentage of brachial artery diameter |
| Combination Therapy | Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%) | -0.6 Percentage of brachial artery diameter |
p-value: 0.08Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48
Time frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52)
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48 | Week 48 | 100.1 CD4 cells |
| Monotherapy | Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48 | Week 24 | 6 CD4 cells |
| Combination Therapy | Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48 | Week 24 | -12 CD4 cells |
| Combination Therapy | Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48 | Week 48 | 60 CD4 cells |
Secondary
Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
The Homeostatic Model Assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. HOMA-IR is reflected in the diminished effect of insulin on hepatic glucose production. HOMA-IR is calculated as: (Glucose \[mg/dL\] X Insulin \[pmol/L\]) / (405 X 6.945). Higher scores indicate worse insulin resistance.
Time frame: Baseline, Week 24, and Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 24 | -0.2 HOMA score |
| Monotherapy | Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 48 | -0.6 HOMA score |
| Combination Therapy | Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 24 | -0.3 HOMA score |
| Combination Therapy | Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Week 48 | -0.5 HOMA score |
p-value: 0.83Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score
The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of a participant. It is calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, and systolic blood pressure. The framingham risk score is calculated as: for males: 0 point (1 percentage) up to 17 points (30 percentages); whereas for females: 0 to 9 points (1 percentage) up to 25 points (30 percentage). Higher scores indicate high cardiovascular risk.
Time frame: Baseline, Week 24, and Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score | Week 24 | 0 Framingham risk score |
| Monotherapy | Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score | Week 48 | 1 Framingham risk score |
| Combination Therapy | Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score | Week 24 | 0 Framingham risk score |
| Combination Therapy | Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score | Week 48 | 1 Framingham risk score |
p-value: 0.66Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL
Time frame: Baseline, Week 24, and Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL | Week 24 | -1 mg/dL |
| Monotherapy | Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL | Week 48 | -4 mg/dL |
| Combination Therapy | Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL | Week 24 | -6 mg/dL |
| Combination Therapy | Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL | Week 48 | -6 mg/dL |
p-value: 0.12Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL
Time frame: Baseline (Day1 of Week 1), Week 24, and Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL | Week 24 | 17 mg/dL |
| Monotherapy | Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL | Week 48 | 14 mg/dL |
| Combination Therapy | Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL | Week 48 | 5 mg/dL |
| Combination Therapy | Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL | Week 24 | 6 mg/dL |
p-value: 0.02Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides
Time frame: Baseline, Week 24, and Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides | Week 24 | 15 mg/dL |
| Monotherapy | Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides | Week 48 | 24 mg/dL |
| Combination Therapy | Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides | Week 24 | -1 mg/dL |
| Combination Therapy | Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides | Week 48 | 6 mg/dL |
p-value: 0.71Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%)
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%) | -4.4 Percentage of brachial artery diameter |
| Combination Therapy | Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%) | -3 Percentage of brachial artery diameter |
p-value: 0.88Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Circulating Endothelial Cells
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Circulating Endothelial Cells | Baseline | 5.09 Endothelial cells |
| Monotherapy | Change From Baseline to Week 48 in Circulating Endothelial Cells | Week 48 | 37 Endothelial cells |
| Combination Therapy | Change From Baseline to Week 48 in Circulating Endothelial Cells | Baseline | 14.6 Endothelial cells |
| Combination Therapy | Change From Baseline to Week 48 in Circulating Endothelial Cells | Week 48 | 64 Endothelial cells |
p-value: 0.37Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score | 0.2 T score |
| Combination Therapy | Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score | -0.1 T score |
p-value: 0.11Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score | 0.2 Z score |
| Combination Therapy | Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score | 0.0 Z score |
p-value: 0.18Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total)
Leg fat content will be analyzed by Dual Energy X-ray Absortiometry (DEXA scan).
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) | -57 Percentage of fat |
| Combination Therapy | Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) | -288 Percentage of fat |
p-value: 0.76Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score | 0.1 T score |
| Combination Therapy | Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score | 0.0 T score |
p-value: 0.03Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score | 0.1 Z score |
| Combination Therapy | Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score | 0.0 Z score |
p-value: 0.04Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells | Baseline | 16 Endothelial cells |
| Monotherapy | Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells | Week 48 | 120 Endothelial cells |
| Combination Therapy | Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells | Baseline | 18 Endothelial cells |
| Combination Therapy | Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells | Week 48 | 108 Endothelial cells |
p-value: 0.66Nonparametric Wilcoxon rank sum test
Secondary
Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT)
Visceral fat content in abdomen will be analyzed with median change in VAT by an abdomen Computerized Tomography.
Time frame: Baseline to Week 48
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monotherapy | Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT) | -4 cm square |
| Combination Therapy | Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT) | -4 cm square |
p-value: 0.56Nonparametric Wilcoxon rank sum test
Secondary
Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL
Time frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52)
Population: Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Screening (Week -4) | 0 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 1 (Day 1) | 1 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 4 | 0 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 12 | 0 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 24 | 0 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 36 | 2 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 48 | 1 Participants |
| Monotherapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Follow up (Week 52) | 2 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Follow up (Week 52) | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Screening (Week -4) | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 24 | 1 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 1 (Day 1) | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 48 | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 4 | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 36 | 0 Participants |
| Combination Therapy | Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL | Week 12 | 1 Participants |
p-value: 0.31Nonparametric Wilcoxon rank sum test