E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous 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 assess the safety of 2 fixed doses of EVP-6124 (2 or 3 mg daily) for up to 52 weeks in subjects with Alzheimer’s disease (AD) who complete (Day 182) studies EVP-6124-024 or EVP-6124-025 |
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E.2.2 | Secondary objectives of the trial |
To assess the duration of clinical effects of EVP-6124 for up to 52 weeks on the following endpoints:
• Cognition using the Mini-Mental State Examination (MMSE)
• Psychiatric and behavioral symptoms using the Neuropsychiatric Inventory (NPI)
• Quality of life using the EuroQol-5D™ (EQ-5D), pharmacoeconomic outcomes using the Resource Utilization in Dementia (RUD-Lite© 3.3), and caregiver perceived burden using the Zarit Burden Interview (ZBI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent form (ICF) for this extension study signed by the subject or legally acceptable representative and an ICF signed by the support person/caregiver before initiation of any study-specific extension procedures
2. Successful completion (Day 182) of study EVP-6124-024 or EVP-6124-025
3. No clinically significant change in the judgment of the investigator in the subject’s medical status during study EVP-6124-024 or EVP-6124-025
4. In the judgment of the investigator, extension treatment is in the best interest of the subject
5. Fertile, sexually active subjects (men and women) must use an effective method of contraception during the study. Female subjects and the female partner of male subjects must be surgically sterile (hysterectomy or Protocol EVP-6124-026; 12 September 2013 Page 9 of 66 Forum Pharmaceuticals Inc. CONFIDENTIAL EVP-6124 bilateral tubal ligation), postmenopausal for at least 1-year, or willing to practice adequate methods of contraception if of childbearing potential (defined as consistent use of combined effective methods of contraception [including at least 1 barrier method])
6. Reliable and capable support person/caregiver, who if not living in the same household, interacts with the subject approximately 4 times per week and will be available to attend clinic visits in person when possible |
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E.4 | Principal exclusion criteria |
1. Significant risk of suicidal or violent behavior in the judgment of the investigator
2. Adverse events (AEs) from the previous study (EVP-6124-024 or EVP-6124-025) that have not resolved, are moderate or severe, judged to be possibly related or related to study drug, and considered by the investigator to be a contraindication to extension study participation
3. Any condition that would make the subject in the judgment of the investigator unsuitable for the study
4. Female subjects who are pregnant, nursing, or planning to become pregnant during the extension study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints for this study include the mean change from baseline to Day 182 in the Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
(MMSE) : baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
(NPI): baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints for this study include the mean change from baseline to Day 182 in the Resource Utilization in Dementia (RUD-Lite© 3.3), Zarit Burden Interview (ZBI), EuroQol-5D (EQ-5D) and Geriatric Depression Scale (GDS). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Resource Utilization in Dementia (RUD-Lite© 3.3): baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
Zarit Burden Interview (ZBI): baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
EuroQol-5D (EQ-5D): baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
Geriatric Depression Scale (GDS): baseline (Extension Study Day 1) and Days 84 and 182 or early termination.
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Portugal |
South Africa |
Spain |
United Kingdom |
United States |
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |