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 | 10020161 |
E.1.2 | Term | HIV infection |
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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 |
1) To evaluate the change in total cholesterol, triglycerides, non-HDL-C, and LDL-C associated with the use of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as measured by the mean percent change from baseline in total cholesterol, triglycerides, non-HDL-C, and LDL-C at Week 12. 2) To evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as measured by proportion of patients with viral load <50 copies/mL at Week 24. 3) To evaluate the safety and tolerability of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as assessed by review of the accumulated safety data at Week 24. |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the change in total cholesterol, triglycerides, non-HDL-C, and LDL-C associated with the use of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as measured by the mean percent change from baseline in total cholesterol, triglycerides, non-HDL-C, and LDL-C at Week 24. 2) To evaluate the antiretroviral activity of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as measured by the proportion of patients with viral load <50 copies/mL at Week 48. 3) To evaluate the safety and tolerability of MK-0518 400 mg b.i.d. compared with KALETRA 400/100 mg b.i.d., each in combination with background antiretroviral therapy, as assessed by review of the accumulated safety data at Week 48. . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patient is a male or female at least 18 years of age on the day of signing the informed consent. 2) Patient is HIV positive as determined by enzyme-linked immunosorbent assay (ELISA) or HIV RNA from documented medical history PCR. 3) Patient has documented HIV RNA PCR <50 copies/mL (or bDNA <75 copies/ml) for at least 3 months prior to study entry while on a KALETRA (dosed as 400 mg lopinavir/100 mg ritonavir twice daily) based regimen, consisting of KALETRA in combinationwith at least 2nRTIs (reverse transcriptase inhibitors), without a change in antiretroviral therapy and with no documentation of HIV RNA ≥50 copies/mL during this time.
Patients followed with other approved sensitvie assays may be permitted to screen folloiwng approval by the Merck Clinical Monitor. 4) Patient has no history of coronary artery disease. 5) Patient has the following laboratory values within 35 days prior to the treatment phase of this study: a. Alkaline phosphatase ≤ 5.0 x upper limit of normal b. AST (SGOT) and ALT (SGPT) ≤ 5.0 x upper limit of normal. 6) Patient has no clinical evidence of active pulmonary disease. 7) Patient who is of reproductive potential agrees to use an acceptable method of birth control, 8) Patient agrees to remain off prohibited concomitant medications as outlined in Section 3.2.1 of the protocol.
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E.4 | Principal exclusion criteria |
1) Patient is receiving a KALETRA based regimen that includes Stavudine (d4T) as a component of the background antiretroviral therapy. 2) Patient is receiving a KALETRA based regimen that includes a second protease inhibitor in addition to KALETRA. 3) Patient is currently receiving, or has received in the past twelve weeks, agents known to have an effect on lipid levels (for example: fish oils, lipidol, bile-acid sequestrants, HMG-CoA reductase inhibitors [such as simvastatin, atorvastatin, rosuvastatin], ezetimibe, ezetimibe/simvastatin, fibrates, niacin, plant sterols, and/or red yeast). 4) Patient has a medical history which includes diabetes mellitus. 5) patient has a history or current evidence of any condition, therapy, laboratory .abnormality or other circumstnace that might confound the results of the study. 6) Patient has a history of alchol or other substance abuse. 7) Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signed informaed consent. 8) Patient has ever used any experiemental HIV-integrase inhibitor. 9) Patient has used systemic immunosuppressive therapy (e.g. 20 mg or more of prednisone or equivalent per day)within one month prior treatment in this study. Short courses of corticosteroids (e.g. as for asthma exacerbation)will be allowed. 10) Patient require hemodialysis. 11) patient has significant hypersensitivity or toher contraindication to any of the components of the study drugs. 12) Patient has chronic hepatitis, including chronic hepatitis B and/or C, with unstable liver function tests. This includes patients who, in the opinion of the investigator, have evidence of impairment of hepatic function, such as hypoalbuminaemia or porlonged PT and PTT. 13) Patient is pregnant or breastfeeding or expecting to conceive (within the duration of the study). Patient is expecting to donate eggs (within the duration of the study). Patient is expecting to donate sperm (within the duration of the study).
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy - proportion of patients with plasma HIV RNA < 50 copies/mL at Week 24. Safety - mean percent changes from baseline in total cholesterol, triglycerides, non-HDL-C, and LDL-C at Week 12.
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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 | 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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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
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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 | 2 |
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 | 2 |