E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
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 | 10020162 | E.1.2 | Term | HIV infection CDC Group I | |
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 | 1.To evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA™, as measured by proportion of patients achieving HIV RNA <50 copies/mL at Week 48. 2.To evaluate the safety and tolerability of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA™, as assessed by review of the accumulated safety data at Week 48. | |
E.2.2 | Secondary objectives of the trial | 1.Evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA™, as measured by the following parameters at Week 48: proportion of patients achieving HIV RNA <400 copies/mL, change from baseline in CD4 cell counts and at Week 96: proportion of patients achieving HIV RNA <50 copies/mL, proportion of patients achieving HIV RNA <400 copies/mL, change from baseline in CD4 cell counts. 2.To evaluate the safety and tolerability of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA™, as assessed by review of the accumulated safety data up to Week 96. 3.To evaluate the nervous system symptoms associated with the use of MK-0518 400 mg b.i.d. compared with efavirenz 600 mg q.h.s., each in combination therapy with TRUVADA™, as measured by proportion of patients with nervous system symptoms assessed by review of accumulated safety data up to Week 8. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | Patient is a male or female at least 18 years of age Patient is naïve to ART Patient is HIV positive as determined by a positive result by enzyme-linked immunosorbent assay (ELISA) and has screening plasma HIV RNA (determined by the central laboratory) >5000 copies/mL within 60 days prior to the treatment phase of this study, and is indicated for treatment based on physician assessment. Local treatment guidelines should be considered in the decision to initiate therapy. Patient has the following laboratory values: •Serum creatinine ≤2.0 x upper limit of normal •Alkaline phosphatase ≤5.0 x upper limit of normal •AST (SGOT) and ALT (SGPT) ≤5.0 x upper limit of normal Patient has a calculated creatinine clearance at time of screening >30 mL/min, based on the Cockcroft-Gault equation which is as follows (and 0.85X this value for females): Clcr (mL/min) = (140-age) x weight (in kg)/72 x serum creatinine (mg/dL) In the opinion of the investigator, the patient should be considered clinically stable with no signs or symptoms of active infection, at the time of entry into the study; i.e., clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study | |
E.4 | Principal exclusion criteria | Patient has been treated for a viral infection other than HIV, such as hepatitis B, with an agent that is active against HIV including but not limited to adefovir, tenofovir, emtricitabine or lamivudine. Note: Patients may be enrolled if treatment occurred prior to the diagnosis of HIV. Patient has documented resistance to tenofovir, emtricitabine, and/or efavirenz. Patient has used another experimental HIV-integrase inhibitor Patient has a current (active) diagnosis of acute hepatitis due to any cause. Patients with chronic hepatitis, including chronic hepatitis B and/or C, may enter the study as long as they have stable liver function tests and meet all inclusion criteria. Patients who, in the opinion of the investigator, have evidence of impairment of hepatic synthetic function, such as hypoalbuminemia or prolonged PT and PTT should be excluded. Patient has used systemic immunosuppressive therapy within one month prior to treatment in this study. Short courses of corticosteroids (e.g., as for asthma exacerbation) will be allowed. Patient requires hemodialysis. | |
E.5 End points |
E.5.1 | Primary end point(s) | Efficacy: Proportion of patients achieving HIV RNA <50 copies/mL at Wk 48 Safety:Proportion of patients with adverse experiences for the following clinical adverse experiences: 1) at least one; 2)drug related; 3) serious; 4) serious and drug related; 5) discontinued study therapy due to an adverse experience. Proportion of patients with any specified nervous system adverse experience. | |
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 | No |
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) | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |