A Phase 2 interventional study of Darunavir(DRV) and Ritonavir in Human Immunodeficiency Virus 1, sponsored by Janssen-Cilag S.p.A.. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-06-27.
Sponsored by Janssen-Cilag S.p.A. · Phase 2, Interventional, and Treatment
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.
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.
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This study's enrollment of 30 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.
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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
Exclusion Criteria:
Monotherapy: darunavir/ritonavir (DRV/r) will be administered for 48 weeks.
Drug: Darunavir(DRV) · Drug: Ritonavir
DRV/r along with 2 nucleoside reverse transcriptase inhibitors (NRTIs) will be administered for 48 weeks and whenever possible, participants should take these medications at the same time. Switch of NRTIs will be allowed in the event of suspected toxicity/intolerance, providing this change can be linked to a documented adverse event (AE)/serious AE.
Drug: Darunavir(DRV) · Drug: Ritonavir · Drug: 2 nucleoside reverse transcriptase inhibitors (NRTIs)
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
Also known as: Prezista
Oral administration of tablet ritonavir 100 mg once daily at the same time, within 30 minutes after food for 48 weeks
2 NRTIs will be administered as per the package inserts.
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
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
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)
Change From Baseline to Week 48 in Circulating Endothelial Cells
Time frame: Baseline to Week 48
Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells
Time frame: Baseline to Week 48
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
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
Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides
Time frame: 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)
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
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
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
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
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
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
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
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
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)
30 participants were enrolled at a single site in Italy.
| Milestone | Monotherapy | Combination Therapy |
|---|---|---|
| Started | 15 | 15 |
| Completed | 15 | 15 |
| Not completed | 0 | 0 |
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.
| Percentage of brachial artery diameter | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%) | -4.8 (-7.0 to 0.3) | -0.6 (-4.7 to 3.3) |
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.
| Percentage of brachial artery diameter | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%) | -4.4 (-6.2 to 2.6) | -3 (-4.5 to 4.0) |
| Participants | Monotherapy | Combination Therapy |
|---|---|---|
| Screening (Week -4) | 0 (-6.2 to 2.6) | 0 (-4.5 to 4.0) |
| Week 1 (Day 1) | 1 | 0 |
| Week 4 | 0 | 0 |
| Week 12 | 0 | 1 |
| Week 24 | 0 | 1 |
| Week 36 | 2 | 0 |
| Week 48 | 1 | 0 |
| Follow up (Week 52) | 2 | 0 |
| Endothelial cells | Monotherapy | Combination Therapy |
|---|---|---|
| Baseline | 5.09 (0 to 105.6) | 14.6 (0 to 551.4) |
| Week 48 | 37 (0 to 5533) | 64 (0 to 4256) |
| Endothelial cells | Monotherapy | Combination Therapy |
|---|---|---|
| Baseline | 16 (0 to 60) | 18 (0 to 93) |
| Week 48 | 120 (0 to 519) | 108 (0 to 715) |
| mg/dL | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | 17 (0 to 40) | 6 (-17 to 20) |
| Week 48 | 14 (7 to 42) | 5 (-12 to 19) |
| mg/dL | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | -1 (-6 to 3) | -6 (-9 to 4) |
| Week 48 | -4 (-5 to 0) | -6 (-11 to -1) |
| mg/dL | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | 15 (-18 to 42) | -1 (-28 to 25) |
| Week 48 | 24 (-15 to 64) | 6 (-8 to 38) |
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.
| HOMA score | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | -0.2 (-1.4 to 0.6) | -0.3 (-1.1 to 0.3) |
| Week 48 | -0.6 (-1.1 to 0.0) | -0.5 (-1.6 to -0.1) |
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.
| Framingham risk score | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | 0 (0 to 1) | 0 (-1 to 3) |
| Week 48 | 1 (0 to 2) | 1 (0 to 3) |
Leg fat content will be analyzed by Dual Energy X-ray Absortiometry (DEXA scan).
| Percentage of fat | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) | -57 (-447 to 419) | -288 (-794 to 601) |
Visceral fat content in abdomen will be analyzed with median change in VAT by an abdomen Computerized Tomography.
| cm square | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT) | -4 (-38 to 4) | -4 (-15 to 19) |
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.
| T score | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score | 0.2 (-0.1 to 0.4) | -0.1 (-0.2 to 0.2) |
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.
| Z score | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score | 0.2 (-0.1 to 0.4) | 0.0 (-0.1 to 0.2) |
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.
| T score | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score | 0.1 (0.0 to 0.3) | 0.0 (-0.2 to 0.1) |
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.
| Z score | Monotherapy | Combination Therapy |
|---|---|---|
| Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score | 0.1 (0.0 to 0.3) | 0.0 (-0.2 to 0.1) |
| CD4 cells | Monotherapy | Combination Therapy |
|---|---|---|
| Week 24 | 6 (-48 to 58) | -12 (-67 to 70) |
| Week 48 | 100.1 (32 to 135) | 60 (-69 to 122) |
Collected over 52 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Monotherapy | — | 0/15 (0%) | 10/15 (66.7%) |
| Combination Therapy | — | 0/15 (0%) | 11/15 (73.3%) |
| Event | Monotherapy | Combination Therapy |
|---|---|---|
| Blood cholesterol increasedInvestigations | 4/15 | 0/15 |
| Low density lipoprotein increasedInvestigations | 4/15 | 0/15 |
| DiarrhoeaGastrointestinal disorders | 1/15 | 3/15 |
| PyrexiaGeneral disorders | 3/15 | 1/15 |
| InfluenzaInfections and infestations | 2/15 | 1/15 |
| Blood creatine phosphokinase increasedInvestigations | 0/15 | 2/15 |
| InsomniaPsychiatric disorders | 2/15 | 0/15 |
| MalaiseGeneral disorders | 1/15 | 1/15 |
| Blood triglycerides increasedInvestigations | 1/15 | 1/15 |
| HeadacheNervous system disorders | 1/15 | 1/15 |
| Age Continuous(Years) | Monotherapy | Combination Therapy | Total |
|---|---|---|---|
| Median | 44.8 (34.5 to 55.1) | 43.0 (35.0 to 46.8) | 44.6 (35.0 to 47.4) |
| Sex: Female, Male(Participants) | Monotherapy | Combination Therapy | Total |
|---|---|---|---|
| Female | 3 | 4 | 7 |
| Male | 12 | 11 | 23 |
| Race/Ethnicity, Customized(Participants) | Monotherapy | Combination Therapy | Total |
|---|---|---|---|
| White | 14 | 15 | 29 |
| Black | 1 | 0 | 1 |
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Acquired Immunodeficiency Syndrome→
Janssen-Cilag S.p.A.