| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| This randomised, controlled, open-label trial will be conducted in HIV-1-infected patients who have received no previous antiretroviral treatment (of more than 7 days in total). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020161 |
| E.1.2 | Term | HIV infection |
|
| 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 |
| The aim of this clinical trial is to compare the efficacy and safety of RTV-boosted atazanavir with nevirapine in two different dosing schedules, each on a background of emtricitabine and tenofovir DF. |
|
| E.2.2 | Secondary objectives of the trial |
•Change in fasting plasma levels of total cholesterol and in its fractions (HDLC and LDLC), the TC : HDLC ratio, in apolipoprotein A1 and B, hsCRP and total triglyceride levels from baseline to after 48, 96 and 144 weeks of treatment
•Change in the estimated cardiovascular risk using the Framingham algorithm of the patients in each treatment group from baseline to after 48, 96 and 144 weeks of treatment
•Change in quality of life from baseline to after 24, 48, 96 and 144 weeks of treatment
•Cost-effectiveness of each treatment regimen in the time periods from baseline to after 24, 48, 96 and 144 weeks of treatment
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Metabolic sub-study, see Section 5.3.1 of protocol: The metabolic sub-study may be performed in the following countries: Australia, Canada, Italy, Mexico, Poland, Romania, Spain, and in the United States.
In the metabolic sub-study the endpoints include (for details please refer to Section 5.3.2 of the protocol):
•Incidence and severity of lipodystrophy and of serum lipid and glycaemic abnormalities.
•Change in NMR (nuclear magnetic resonance spectroscopy) lipoprotein profiles (LDL, HDL, IDL, and VLDL particle number and size), and change in insulin, adinopectin, leptin plasma levels.
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|
| E.3 | Principal inclusion criteria |
1.Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation
2.HIV-1-infected males or females ≥ 18 years of age with positive serology (ELISA) confirmed by Western blot or equivalent test method
3.No previous antiretroviral treatment (of more than 7 days)
4.Males with CD4+ counts of < 400 cells/mm3 and females with CD4+ counts of < 250 cells/mm3
5.NVP- and ATZ/r susceptibility based on HIV-1 genotypic resistance report
6.Adequate renal function defined as a calculated creatinine clearance (CLCr) ≥ 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).
7.Karnofsky score ≥ 70
8.Acceptable medical history, as assessed by the investigator
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|
| E.4 | Principal exclusion criteria |
1.Active drug abuse or chronic alcoholism at the investigator’s discretion
2.Hepatic cirrhosis stage Child-Pugh B or C
3.Female patients of child-bearing potential who:
•have a positive serum pregnancy test at screening or during the study,
•are breast feeding,
•are planning to become pregnant,
•are not willing to use a barrier method of contraception, or are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives
4.Laboratory parameters > DAIDS grade 2 (triglycerides > DAIDS grade 3; total cholesterol no restrictions)
5.Active hepatitis B or C disease, defined as HBsAg-positive or HCV-RNA-positive with AST/ALT > 2.5x ULN (DAIDS grade 1)
6.Hypersensitivity to any ingredients of the test products
7.Patients who are receiving other concomitant treatments which are not permitted, as listed in Appendix 10.6 of the protocol
8.Use of other investigational medications within 30 days before study entry or during the trial
9.Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with prednisone)
10.Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma
11.Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit
12.Patients who are receiving systemic treatment for malignant disease
13.Patients who in the opinion of the investigator are not candidates for inclusion in the study
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the treatment response (TR) at Week 48. TR is defined as HIV viral load of < 50 copies/ml measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of ARV therapy prior to Week 48. If the VL is ≥ 50 copies/ml at Week 48 and this is the first sequential VL value ≥ 50 copies/ml following treatment response, then another measurement at least 2 weeks later is necessary to determine whether rebound has occurred. A rebound is defined by two consecutive measurements of VL ≥ 50 copies/ml, at least two weeks apart, after two consecutive measurements of VL < 50 copies/ml.
A change of ARV therapy is either defined as:
•A permanent discontinuation of study drug or its control
•A change in the dose of ATZ or RTV
A change from NVP once daily to twice daily administration and vice versa is not considered failure for the primary analysis. Therefore, a patient remains a treatment responder in this case if all other criteria are fulfilled.
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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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
Definition see Section 6.2.3 of the protocol:
A post-trial visit will be performed by all patients who complete the entire trial or who are discontinued early. The post-trial visit defines the end of trial overall (last patient out). This post-trial visit must occur 28 to 35 days after the end of trial (EOT) visit. At this visit, the safety of NVP and ATZ/r, following termination of study participation, will be evaluated. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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