E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 investigate whether switching individuals who have central nervous system (CNS) side effects from taking Efavirenz-containing treatment (as Atripla) to Truvada/Raltegravir resolves the CNS side effects after 4 weeks
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E.2.2 | Secondary objectives of the trial |
To investigate whether switching individuals who have central nervous system (CNS) side effects from taking Efavirenz-containing treatment (as Atripla) to Truvada/Raltegravir resolves the CNS side effects after 12 weeks. To investigate the change in CD4 (primary receptor used by HIV-1 to gain entry into host cells)count in individuals switching from Atripla to Truvada/Raltegravir. To investigate continued virus suppression in individuals switching from Atripla to Truvada/Raltegravir. To investigate changes in fasting lipids-cholesterol and triglycerides- in individuals switching from Atripla to Truvada/Raltegravir. To investigate the safety of switching from Atripla to Truvada/efavirenz over 12 weeks To investigate the impact of switching from Atripla to Truvada/raltegravir on drug adherence To investigate the impact of switching from Atripla to Truvada/Raltegravir on CNS side effects as measured by Hospital Anxiety and Depression (HADS) score
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female aged 18 years or above has a documented HIV-1 infection has signed the Informed Consent Form voluntarily is willing to comply with the protocol requirements has an HIV-plasma viral load at screening <50 copies/mL has a CD4 cell count at Screening >50 cells/mm3 has been on a stable ART, with at least 3 licensed agents, one of which being EFV, for at least 12 weeks at Screening, and has been on Atripla for at least 4 weeks at screening; the subject must be willing to stay on treatment until Baseline estimated glomerular filtration rate (by MDRD or CG methods) >50 ml/min. has symptomatic toxicity associated with EFV after at least 12 weeks of therapy if female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs); Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential if a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit |
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E.4 | Principal exclusion criteria |
is infected with HIV-2 is using any concomitant therapy disallowed as per SPC for the study drugs has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions (must be discussed with the sponsor prior to enrolment): Stable cutaneous Kaposi’s Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period CD4 count less than 200 cells/mm3 Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed has acute viral hepatitis including, but not limited to, A, B, or C has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Subjects co-infected with chronic HBV or HCV can enter the trial if clinically stable and not expected to require treatment during the trial period. has received any investigational drug within 30 days prior to the trial drug administration Prior exposure to raltegravir or investigational integrase inhibitors Any tenofovir or emtricitabine associated resistance mutations No baseline resistance test available Clinically significant allergy or hypersensitivity to any trial medication excipients If female, she is pregnant or breastfeeding screening blood results with any grade 3 / 4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed). Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN Resolution of their CNS toxicity between Screening and Baseline visits Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The rate of neuropsychiatric and central nervous system (CNS) toxicity as measured (as defined by the ACTG adverse event scale) after 4 weeks of raltegravir therapy as measured by : i) Sleep questionnaire ii) CNS toxicity questionnaire (based on DAIDS CNS toxicity grading)
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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 | No |
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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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Completion of all trial procedures by participants (e.g. last follow up visit) |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |