E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cognitive function and sleep pattern in HIV-1 patients |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021425 |
E.1.2 | Term | Immune system disorder |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 explore whether chronic Efavirenz therapy is associated with mild cognitive impairment, and if it is improved by switch to Kaletra after 10 weeks. |
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E.2.2 | Secondary objectives of the trial |
1) To explore whether switch from Efavirenz to Kaletra® results in improvement in cerebral metabolites
2) To explore whether switch from Efavirenz to Kaletra® results in improvement in sleep quality
3) To assess recruitment and withdrawal rates and to provide relevant parameter estimates to inform future studies.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Documented HIV-1 RNA viral load (VL) measurement of <50 copies/ml within the 4 months preceding study entry and no VL exceeding 200c/ml within 1 year prior to study entry. This constraint is to remove any CNS effects of active viral replication at baseline, and / or potential change in level of viral replication during the study period
• On HAART (at least 3 anti-retroviral drugs from at least 2 classes) for at least 12 months prior to study entry
• On Efavirenz (EFV, Sustiva) for at least 6 months prior to study entry. This constraint is to remove acute neuropsychiatric effects of EFV which are typically clinically apparent in the first 4-6 weeks of therapy
• Patient has provided written informed consent for participation in the study prior to any study specific procedures
• Age 18 to 65 years inclusive |
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E.4 | Principal exclusion criteria |
• Use of Kaletra or any other HIV protease inhibitor within 6 months of study entry
• Current self-reported (within last 3 months) recreational drug use
• Current self-reported weekly alcohol consumption exceeding 35 units / week
• Known contra-indication to MRI scanning
• Known hypersensitivity to Kaletra, or to ritonavir in pharmacokinetic boosting doses (100 or 200mg Ritonavir daily)
• Currently (within 6 weeks of study entry) receiving interferon therapy for treatment of chronic viral hepatitis, or expected to commence such treatment with the next 4 months
• Severe renal or hepatic impairment
• Pregnancy, or women planning to become pregnant within next 6 months
• breastfeeding
• Use of other investigational study drugs within 30 days prior to study entry (defined as date of randomisation into study)
• Patients on drugs that will interact with Efavirenz and should not be co-administered including: Terfenadine, Astemizole, Cisapride, Midazolam, Triazolam, Pimozide, Bepridil, or ergot alkaloids (for example, Ergotamine, Dihydroergotamine, Ergonovine and Methylergonovine) because competition for CYP3A4 by Efavirenz could result in inhibition of metabolism and create the potential for serious and/or life-threatening undesirable effects (for example, cardiac arrhythmias, prolonged sedation or respiratory depression), herbal preparations containing St. John's wort (Hypericum perforatum).
• Patients on drugs that will interact with Kaletra and should not be co-administered including: Terfenadine, Astemizole, Cisapride, Midazolam, Triazolam, Pimozide, Alfuzosin, Amiodarone, Fusidic Acid, Dihydroergotamine, Ergonovine, Ergotamine, Methylergonovine, Lovastatin, Simvastatin Sildenafil, Vardenafil, herbal preparations containing St. John's wort (Hypericum perforatum), Rivaroxaban.
• Previous participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is change from baseline of CogState neurocognitive score in HIV-1 patients 10 weeks following switch from EFV to Kaletra.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary outcome measure (change in neurocognitive function) will be measured at week 10 of treatment. |
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E.5.2 | Secondary end point(s) |
1. Change from baseline of cerebral metabolites as assessed by MRS in HIV-1 patients 10 weeks following switch from EFV to Kaletra.
2. Change from baseline in resting-state and attentional processing task-based fMRI in HIV-1 patients 10 weeks following switch from EFV to Kaletra
3. Change from baseline of sleep quality in HIV-1 patients 10 weeks following switch from EFV to Kaletra.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary outcome measure of change in MRS and fMRI will be measured at study week 13. The secondary outcome measure of change in sleep will be measured by diary completion from weeks 13-15, and questionnaire at study week 13. |
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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 | No |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Baseline measurements prior to switch from EFV. Not a comparator. |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |