A Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients (MONARCH)
This study has been completed.
Sponsor:
Janssen-Cilag S.p.A.
Information provided by (Responsible Party):
Janssen-Cilag S.p.A.
ClinicalTrials.gov Identifier:
NCT01391013
First received: June 23, 2011
Last updated: January 30, 2013
Last verified: January 2013
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Purpose
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 patients.
| Condition | Intervention | Phase |
|---|---|---|
|
Human Immunodeficiency Virus-1 |
Drug: Darunavir(DRV) Drug: Ritonavir Drug: 2 nucleoside reverse transcriptase inhibitors (NRTIs) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomised, Controlled, Open-Label Trial to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg O.D. Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Subjects With Undetectable Plasma HIV-1 RNA on Their Current Treatments. |
Resource links provided by NLM:
Genetics Home Reference related topics:
complement factor I deficiency
MedlinePlus related topics:
HIV/AIDS
U.S. FDA Resources
Further study details as provided by Janssen-Cilag S.p.A.:
Primary Outcome Measures:
- Change in brachial artery flow mediated vasodilatation (FMD) from baseline to Week 24 [ Time Frame: Week 1 (Day 1) and Week 24 ] [ Designated as safety issue: No ]Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter.
Secondary Outcome Measures:
- Change in brachial artery FMD from baseline to Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]
- Number of patients with a human immunodeficiency virus- ribonucleic acid less than 50 copies/mL at Week 48 [ Time Frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up visit ] [ Designated as safety issue: No ]
- Change in circulating endothelial cells and their precursors from baseline to Week 48 [ Time Frame: Week 1 (Day 1) and Week 48 ] [ Designated as safety issue: No ]
- Change in mean LDL-cholesterol from baseline to Week 24 and Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]
- Change in mean HDL-cholesterol from baseline to Week 24 and Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]
- Change in mean triglycerides from baseline to Week 24 and Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]
- Change in insulin sensitivity from baseline to Week 24 and Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]insulin sensitivity will be calculated by homeostasis model of insulin resistance (HOMA-IR), where HOMA-IR=Insulin (μU/mL) x Blood glucose (mmol/L)/22,5
- Change in mean Framingham risk score from baseline to Week 24 and Week 48 [ Time Frame: Week 1 (Day 1), Week 24, and Week 48 ] [ Designated as safety issue: No ]The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of a patient. 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).
- Change in leg fat content and visceral fat content in abdomen from baseline to Week 48 [ Time Frame: Week 1 (Day 1) and Week 48 ] [ Designated as safety issue: No ]Leg fat content will be analyzed by Dual Energy X-ray Absorptiometry (DEXA scan) while visceral fat content in abdomen will be analyzed by abdomen Computerized Tomography.
- The study medication toxicity from baseline to Week 48 [ Time Frame: Week 1 (Day 1) and Week 48 ] [ Designated as safety issue: No ]The study medication toxicity is measure on mitochondrial deoxyribonucleic acid (mtDNA). The mtDNA will be quantified as the amount of mtDNA per cell in isolated cluster of differentiation (CD) 4+ T cell or CD8+ (if not achievable with CD4+ T cells) and soluble factors involved in mitochondrial/metabolic alterations (leptin, adiponectin).
- Change in lumbar and femoral neck T and Z score from baseline to Week 48 [ Time Frame: Week 1 (Day 1) and Week 48 ] [ Designated as safety issue: No ]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 the patient. Z score is the number of standard deviations above or below the mean for the patient's age, sex and ethnicity. These scores are calculated from patients' age, gender and race and skeletal site.
- Change in CD4-cell count from baseline over 48 weeks [ Time Frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up visit ] [ Designated as safety issue: No ]
- Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Up to Week 56 ] [ Designated as safety issue: Yes ]
| Enrollment: | 30 |
| Study Start Date: | June 2009 |
| Study Completion Date: | April 2011 |
| Primary Completion Date: | April 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Monotherapy
Monotherapy: darunavir/ritonavir (DRV/r) will be administered for 48 weeks.
|
Drug: Darunavir(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
Other Name: Prezista
Drug: Ritonavir
Oral administration of tablet ritonavir 100 mg once daily at the same time, within 30 minutes after food for 48 weeks
|
|
Experimental: Combination therapy
DRV/r along with 2 nucleoside reverse transcriptase inhibitors (NRTIs) will be administered for 48 weeks and whenever possible, patients 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)
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
Other Name: Prezista
Drug: Ritonavir
Oral administration of tablet ritonavir 100 mg once daily at the same time, within 30 minutes after food for 48 weeks
Drug: 2 nucleoside reverse transcriptase inhibitors (NRTIs)
2 NRTIs will be administered as per the package inserts.
|
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 patients 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). Patients 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 patients 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria: - Human immunodeficiency virus-1 (HIV-1) infected patients 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
- Patients' 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 cp/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 patients
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
- Patients 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
Contacts and Locations More Information
No publications provided
| Responsible Party: | Janssen-Cilag S.p.A. |
| ClinicalTrials.gov Identifier: | NCT01391013 History of Changes |
| Other Study ID Numbers: | CR017575, TMC114HIV3017, TMC-C-07-IT-016 |
| Study First Received: | June 23, 2011 |
| Last Updated: | January 30, 2013 |
| Health Authority: | Italy: AIFA - Italian Medicines Agency |
Keywords provided by Janssen-Cilag S.p.A.:
|
Human immunodeficiency virus-1 Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndrome Darunavir/ritonavir |
Darunavir Ritonavir Nucleoside reverse transcriptase inhibitors (NRTIs) Prezista |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases Reverse Transcriptase Inhibitors Ritonavir |
Darunavir Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses HIV Protease Inhibitors Protease Inhibitors Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 22, 2013