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:
Information provided by (Responsible Party):
Janssen-Cilag S.p.A.
ClinicalTrials.gov Identifier:
NCT01391013
First received: June 23, 2011
Last updated: May 22, 2013
Last verified: May 2013
  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 participants.


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:


Further study details as provided by Janssen-Cilag S.p.A.:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%) [ Time Frame: Baseline (Day 1 of Week 1) to Week 24 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%) [ Time Frame: Baseline to Week 48 ] [ 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. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.

  • 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) ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 48 in Circulating Endothelial Cells [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides [ Time Frame: Baseline, Week 24, and Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline, Week 24, and Week 48 ] [ Designated as safety issue: No ]
    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 in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score [ Time Frame: Baseline, 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 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.

  • Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52) ] [ Designated as safety issue: No ]

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, 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)
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 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.

  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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01391013

Sponsors and Collaborators
Janssen-Cilag S.p.A.
Investigators
Study Director: Janssen-Cilag S.p.A. Clinical Trial Janssen-Cilag S.p.A.
  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
Results First Received: February 13, 2013
Last Updated: May 22, 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 April 16, 2014