E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038997 |
E.1.2 | Term | Retroviral infections |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of 400 mg QD nevirapine extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR) in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
To evaluate safety and pharmacokinetics of NVP XR and NVP IR |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation -HIV-1 infected males or females >=18 years of age with positive serology (ELISA) confirmed by Western blot -No previous antiretroviral treatment -Males with CD4+ counts >50 - <400 cells/microL or females with CD4+ counts >50 - <250 cells/microL -Adequate renal function defined as a calculated creatinine clearance (CLCr) greater than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows: Male: (140 age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) = CLCr (mL/min). Female: (140 age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) x 0.85 = CLCr (mL/min). -Karnofsky score >70 -An HIV-1 viral load of >=1,000 copies/microL -Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important opportunistic infections -Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system during the study. |
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E.4 | Principal exclusion criteria |
-Active drug abuse or chronic alcoholism at the investigators discretion -Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or HCV-RNA-positive -Female patients of child-bearing potential who: a)have a positive serum pregnancy test at screening, b)are breast feeding, c)are planning to become pregnant, d)are not willing to use a barrier method of contraception, or e)are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives Note: During participation in this study, females and males have to use barrier methods of contraception in addition or instead of ethinyl estradiol containing oral contraceptives. These barrier methods are: diaphragm with spermicide substance, femidome (condom for females), cervical caps and condoms. -Laboratory parameters >DAIDS Grade 2 -ALT/AST > DAIDS Grade 1 -Hypersensitivity to any ingredients of the test products -Previous use of Viramune (nevirapine) or any other antiretroviral agents (does not include use of single dose NVP for the prevention of mother to child transmission) -Resistance to NNRTIs or either one of the components of Truvada (emtricitabine or tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance testing report obtained at screening -Patients who are receiving other concomitant treatments which are not permitted, as described in the prescribing information -Use of investigational medications (any experimental agent other than the study regimen) within 30 days before study entry or during the trial -Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2) -Patients who have been diagnosed with malignant disease -Patients who in the opinion of the investigator are not candidates for inclusion in the study -Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma -Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is virologic response by Week 48. Virologic response is defined as VL <50 copies/mL prior to Week 48 and without subsequent virologic rebound or change of ARV therapy prior to Week 48. A virologic rebound is defined by two consecutive measurements of VL >=500 copies/mL, at least two weeks apart, after the measurement of VL <50 copies/mL. If the first VL >=500 copies/mL occurs at Week 48 and this is the first sequential VL value >=500 copies/mL following virologic response, then another measurement at least two weeks later is necessary to confirm whether virologic rebound has occurred. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |