E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment-naïve, HIV-1 infected subjects |
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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 | 10020162 |
E.1.2 | Term | HIV infection CDC Group I |
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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 compare the safety and tolerability of lopinavir-ritonavir (LPV/r) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) with a nucleoside-sparing regimen consisting of lopinavir/ritonavir + raltegravir (RLT). ● To compare the antiviral efficacy of LPV/r +FTC/TDF and LPV/r+RLT after 48 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
● To compare antiviral efficacy of LPV/r +FTC/TDF and LPV/r+RLT at 96 weeks of treatment. ● To compare viral decay rates between LPV/r +FTC/TDF and LPV/r+RLT. ● To characterize the development of resistance in the two treatment groups. ● To compare the population pharmacokinetics of lopinavir and ritonavir between the LPV/r +FTC/TDF and LPV/r+RLT regimens. ● To compare the effect of LPV/r +FTC/TDF and LPV/r+RLT on metabolic and somatic parameters. ● To compare the effect of LPV/r +FTC/TDF and LPV/r+RLT on patient reported outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. At least 18 years of age. 2. Naïve to antiretroviral treatment (< 7 days of any antiretroviral treatment therapy > 30 days prior to study drug administration). 3. No prior treatment with an HIV-1 integrase inhibitor. 4. If the subject has been treated for an active AIDS-defining opportunistic infection (as denoted by * in Appendix D) within 45 days of planned study drug initiation, but is clinically stable and on stable maintenance therapy, the subject may be eligible for participation in the study, only after the investigator contacts the Abbott Medical Monitor to discuss the issue. 5. Does not require and agrees not to take any drugs that are contraindicated or have significant pharmacokinetic interactions with study drugs during the course of the study. For complete information, refer to the most current product label for locally approved prescribing information for lopinavir/ritonavir (Kaletra®), co-formulated emtricitabine/tenofovir disoproxil fumarate (Truvada®), and raltegravir (Isentress™). 6. Will notify the principal investigator of any drugs taken during the study, including over-the-counter medicines, vitamins, minerals, or herbal remedies. 7. Not breast-feeding. 8. Voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed. 9. If female, subject must be either postmenopausal for at least one year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or she must use a non-hormonal method of birth control that is acceptable to both the subject and investigator, and is consistent with the locally approved prescribing information for lopinavir/ritonavir. ● All female subjects must have a urine pregnancy test performed at the Screening Visit and on Day -1/Baseline, and results of both tests must be negative. 10. Vital signs, physical examination and laboratory results do not exhibit evidence of acute illness. 11. Plasma HIV-1 RNA level of greater than or equal to 1,000 copies/mL at Screening and in the investigator's opinion requires antiretroviral therapy. |
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E.4 | Principal exclusion criteria |
1. History of an allergic reaction or significant sensitivity to lopinavir/ritonavir, emtricitabine/tenofovir disoproxil fumarate, or raltegravir. 2. Resistance to lopinavir/ritonavir, tenofovir or emtricitabine based on the HIV-1 drug resistance genotypic test results at the Screening Visit. 3. Ongoing history of recreational drug or alcohol use, or a psychiatric illness that could preclude adherence with the protocol. 4. Significant medical history of concomitant illness or disease that would adversely affect his/her participating in this study. 5. Any investigational drug or investigational vaccine received within 30 days prior to study drug administration. 6. The investigator considers the subject to be an unsuitable candidate for the study. 7. Any of the following abnormal screening results: ● Hemoglobin ≤ 8.0 g/dL ● Absolute neutrophil count ≤ 750 cells/μL ● Platelet count ≤ 50,000 per mL ● ALT (SGPT) or AST (SGOT) ≥ 3.0 × Upper Limit of Normal (ULN) ● Calculated creatinine clearance < 50 mL/min ● Hepatitis B surface antigen HBsAg is positive |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with HIV-1 RNA < 50 copies/mL at 48 weeks |
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2 treatment combinations compared |
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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.8.4.1 | 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 | 25 |
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 |