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 | LLT |
E.1.2 | Classification code | 10049826 |
E.1.2 | Term | Blood HIV RNA |
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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 assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant. To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant. To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. HIV-1-infected, clinically stable with no AIDS-defining events 2. Adults, aged 18 years - 65 years 3. Sexually active men with partners of childbearing potential and women of childbearing potential (WOCBP, defined as a woman biologically capable of becoming pregnant, includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives) must agree to use an acceptable form of contraception (as determined by the investigator) during participation in the study and for 30 days after the last dose of study drug 4. Plasma HIV-1 RNA levels 5,000 - 150,000 copies/mL at screening (Amplicor HIV-1 Monitor Test, version 1.5, Roche Diagnostic) 5. Genotypically documented M184V variant as assessed by a Trugene HIV-1 kit 6. Positive HIV-1 genotype for K103N if currently receiving Efavirenz or Nevirapine 7. Receiving a stable antiretroviral regimen (defined as no change in antiretroviral therapy for at least 4 weeks prior to randomization) that includes lamivudine or emtricitabine 8. CD4 count of greater or equal to 100 cells/mL 9. Acceptable hematologic and chemistry parameters as follows: Hemoglobin greater or equal to 11 g/dL Absolute neutrophil count (ANC) greater or equal to 2000 cells/mm3 Platelets greater or equal to 100,000 cells/mm3 Alanine transaminase (ALT)/aspartate transaminase (AST) greaer or equal to 1.5 times the upper normal limit (UNL) Bilirubin ≤ 1.5 times UNL 10. Subjects must be able to provide written informed consent prior to screening. |
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E.4 | Principal exclusion criteria |
1. Hepatitis B surface antigen (HBsAg) positive, and/or HBV DNA positive 2. HIV-1 genotype positive for greater or equal to 4 protease primary mutations 3. HIV-1 genotype positive for greater or equal to 2 non-nucleoside reverse transcriptase inhibitors mutations 4. Previous therapy with agents with significant systemic myelosuppressive or cytotoxic potential within 3 months of Study Day 1 or the expected need for such therapy after Study Day 1 5. Previous use or need for bone marrow colony stimulating factors such as erythropoietin (Epogen or Procrit) or filgrastim (Neupogen), etc 6. Evidence or history of cirrhosis 7. Recent (within 3 months of screening) history of alcohol abuse, physical dependence to any opioid, cocaine, LSD or amphetamines, or history of drug addiction 8. Inability to tolerate oral medication 9. Woman who are pregnant or breastfeeding 10. Any clinical condition or prior therapy that, in the investigators opinion, would make them unsuitable for the study or unable to comply with the dosing requirements 11. Participated in a clinical study involving administration of an investigational drug (new chemical entity), or a marketed drug within the past 30 days of Study Day 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
EFFICACY VARIABLES The primary efficacy endpoint will be defined as a log fall greater or equal to 0.5 in HIV-1 RNA levels from baseline to Day 14. METHODS, FREQUENCY AND TIMING OF EFFICACY DATA COLLECTED On Study Days -3, 1, 7, 10, 14, 21 +/- 1, and 28 +/- 1, blood samples will be drawn to assess plasma HIV-1 RNA levels. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 1 |
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 | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |