A randomised, controlled, opel-label trial to compare the efficacy, safety and tolerability 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.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006437-40-PT
• Date of registration: 02/03/2007
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A randomised, controlled, opel-label trial to compare the efficacy, safety and tolerability 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.
• Scientific title: A randomised, controlled, opel-label trial to compare the efficacy, safety and tolerability 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.
• Date of first enrolment: 01/06/2007
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006437-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: non-inferiority: DRV/r versus DRV/r + 2 NRTIs

Countries of recruitment

Austria, Denmark, Germany, Hungary, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who meet all of the following criteria are eligible for this trial:

Subjects with documented HIV-1 infection.

Male or female ages > 18 years old.

Subjects who have voluntarily signed and dated the consent form.

Subjects currently receiving HAART for at least 24 weeks.
Note: HAART is defined as the combination of 2 NRTIs with at least 1 additional ARV from the NNRTI and/or PI class. A regimen with 3 NRTIs is allowed.

Plasma HIV-1 RNA < 50 copies/mL for at least 24 weeks prior to screening (two results must be documented).

Subjects taking the same ARV combination for at least 8 weeks before screening.

Subject and physician’s preference to change the current HAART regimen for reasons of simplification and/or toxicity (examples of toxicities include but are not limited to: CNS, gastrointestinal disturbances, jaundice, anaemia, nausea, neuropathy, paresthesia, hyperlipidaemia, glucose intolerance or diabetes, nephrolithiasis, lipodystrophy, hepatotoxicity, rash and skin related events, any other AE or intolerability or laboratory abnormalities caused by current HAART).

CD4 > 100/mm(3) at the start of HAART and > 200/mm(3) at screening.

Subjects can comply with the protocol requirements.



Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting one or more of the following criteria cannot be selected for this trial:·

History of virological failure defined as two consecutive plasma HIV-1 RNA > 500
copies/mL while on previous or current antiretroviral therapy.

History of any primary PI mutations as defined by the IAS-USA guidelines 2006.

Clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).

Subjects diagnosed with acute viral hepatitis at screening.

Subjects co-infected with hepatitis B.
Note: Subects co-infected with hepatitis B are disallowed to avoid a flare-up when discontinuing NRTIs. Subjects co-infected with chronic hepatitis C will be allowed to enter the trial if their condition is clinically stable and is not expected to require treatment during the study period. See section 9.3.3.3. of the protocol for further guidelines on enrolment of hepatitis C co-infected subjects.

Subjects with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading table (see addendum 1 of the protocol: DAIDS AE grading Table), with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
-Subjects with pre-existing diabetes or with asymptomatic glucose grade 3 or 4 elevations.
-Subjects with asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.

Presence of any currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions:
-Stable cutaneous Kaposi’s Sarcoma (i.e., no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.
-Wasting syndrome due to HIV infection.
Note: An AIDS defining illness that is not clinically stabilized for at least 30 days will be considered as currently active.

Pregnant or breastfeeding women.

Active drug abuse, including alcohol or recreational drugs, which, in the opinion of the investigator, is expected to interfere with the subject’s ability to adhere to the study procedures and treatment regimen. Subjects on a methadone program will be accepted if deemed appropriate by the investigator.

Previous or current use of darunavir.

Previous or current use of enfuvirtide.

Any active clinically significant disease (e.g., tuberculosis, cardiac dysfunction, pancreatitis, acute viral infections) or life threatening disease or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subject’s safety or outcome of the study.

Any medical or psychiatric condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the trial protocol.

Previously demonstrated clinically allergy or hypersensitivity to any of the excipients of the investigational medication (DRV).
Note: DRV is a sulfonamide. Subjects who have previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and DRV has been identified in subjects participating in phase II trials.

Hypersensitivity to ritonavir or to any of the other ingredients found in the ritonavir tablet.

Use of disallowed concomitant therapy (see Section 4.4 and addendum 3 of protocol)






Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV-1
MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection

Intervention(s)

Product Name: Darunavir ethanolate (formerly known as TMC114)
Product Code: DRV (formely known as TMC114)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: darunavir
CAS Number: 20636-99-1
Current Sponsor code: DRV (formely known as TMC114)
Other descriptive name: Darunavir ethanolate (formerly known as TMC114)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Norvir
Product Name: Norvir
Product Code: rtv
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ritonavir
CAS Number: 155213-67-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To demonstrate non-inferiority in efficacy of DRV/r versus the triple combination therapy containing DRV/r, with respect to confirmed virologic response, defined as plasma HIV-1 RNA < 50 copies/mL at 48, 96 and 144 weeks.

Secondary Objective: Compare
-safety+tolerabilityTreatmentSimplificationRegimen DRV/r monotherapy vs. triple combination therapy containing DRV/r
-immune response in terms changes CD4+T cell count from baseline over 48,96,144 wks treatment simplification regimen by DRV/r monotherapy with triple combination therapy containing DRV/r
-freq. development at least 1 new mutation in RTandPR gene
-changes laboratory parameters at all time points from baseline to 48,96,144wks,both treatment groups
-subject-reported antiretroviral medication adherence at baseline+evolution adherence over 48,96,144 wks,both treatment groups
-antiretroviral drug treatment cost over 48,96,144 wks,both treatment groups
Assess
-incidence+SeverityBodyCompositionChangesOver48,96,144Wks,BothTreatmentGroups
-+compareResolutionToxicitiesPresentAtScreeningVisitOver48,96,144Wks,BothTreatmentGroups
Evaluate
+compareSubject-reported Health-RelatedQuality ofLife (HRQoL)AtBaseline+evolution HRQoL Over48,96,144Wks,BothTreatmentGroups

Primary end point(s): Percentage of subjects with a plasma HIV-1 RNA < 50 copies/mL at Week 48, 96 and 144 by intent to treat (ITT) analyses.

Secondary ID(s)

TMC114HIV3006

2006-006437-40-GB