E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease |
Ziekte van Alzheimer |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 continue assessing the safety and tolerability of ANAVEX2-73. Safety and Tolerability Measures: - Physical examination - Vital signs (heart rate, respiratory rate, systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse oximetry, and oral body temperature) - Graded AEs according to common Terminology Criteria for Adverse Events (CTCAE) V4.0.3 - 12-lead ECG - Columbia-Suicide Severity Rating Scale (C-SSRS) - Clinical laboratory tests (hematology including coagulation, clinical chemistry including lipid panel, and urinalysis) - Concomitant medication documentation |
Continueren met het beoordelen van de veiligheid en verdraagbaarheid van ANAVEX2-73. Metingen voor veiligheid en verdraagbaarheid: • Lichamelijk onderzoek • Vitale functies (hartslag, ademhalingsfrequentie, systolische en diastolische bloeddruk, pulse oximetrie en orale lichaamstemperatuur • Gegradeerde AEs volgend de Terminology Criteria for Adverse Events (CTCAE) v4.0.3 • 12-lead ECG • Columbia-Suicide Severity Rating Scale (C-SSRS) • Laboratorium onderzoek (hematologie, stolling, klinische chemie inclusief lipiden panel en urine analyse) • Documentatie van gelijktijdig genomen medicatie |
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E.2.2 | Secondary objectives of the trial |
• Observation of P-tau blood level concentration • To determine whether ANAVEX2-73 modifies cognition, behavior, or QoL, according to the following standardized measures commonly used in AD: - Change from baseline to week 96 in ADAS-Cog - Change from baseline to week 96 in ADCS-ADL - Change from baseline to week 96 in MMSE - Change from baseline to week 96 in NPI-Q - Change from baseline to week 96 in ZBI - Change from baseline to week 96 in QoL-AD |
• Observeren van de P-tau bloedspiegel • Bepalen of ANAVEX2-73 cognitie, gedrag of QoL wijzigt, volgens aan de volgende gestandaardiseerde metingen die vaak worden gebruikt in AD: - Verandering vanaf baseline tot week 96 in ADAS-Cog - Verandering vanaf baseline tot week 96 in ADCS-ADL - Verandering vanaf baseline tot week 96 in MMSE - Verandering vanaf baseline tot week 96 in NPI-Q - Verandering vanaf baseline tot week 96 in ZBI - Verandering vanaf baseline tot week 96 in QoL-AD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previous completion of participation in the ANAVEX2-73-AD-004 double-blind study. 2. Participants may be either outpatients, or residents of an assisted-living facility. 3. Participants must have a designated study partner, who spends at least 10 hr per week with the participant, in order for assessments (e.g., carer burden instruments) to be completed with sufficient knowledge of the participant. 4. No suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months (i.e., active suicidal thought(s) with intent but without specific plan, or active suicidal thought(s) with plan and intent) OR suicidal behavior in the past 2 years (i.e., actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior). 5. Confirmation from the participant that, if of childbearing potential, is not pregnant through urine pregnancy testing. |
1. Eerdere voltooiing van deelname aan de ANAVEX2-73-AD-004 dubbelblind studie. 2. Deelnemers kunnen zowel poliklinisch zijn als bewoners van begeleid wonen. 3. Deelnemers moeten een aangewezen studiepartner hebben, die minimaal 10 uur per week doorbrengt met de deelnemer, zodat beoordelingen (bijv. instrumenten voor mantelzorg) gedaan kunnen worden met voldoende kennis over de deelnemer. 4. Geen type 4 of 5 zelfmoordgedachten volgens de Columbia Suicide Severity Rating Scale (CSSRS) in de afgelopen 3 maanden (d.w.z. actieve zelfmoordgedachten met intentie maar zonder specifiek plan, of actieve suïcidale gedachten met plan en intentie) OF suïcidaal gedrag in de afgelopen 2 jaar (d.w.z. daadwerkelijke poging, onderbroken poging, afgebroken poging, of voorbereidende handelingen of gedrag). 5. Bevestiging van de deelnemer dat deze, indien in de vruchtbare leeftijd, niet zwanger is door middel van urine-zwangerschapstests.
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E.4 | Principal exclusion criteria |
1. Adverse events (AEs) from the previous study (ANAVEX2-73-AD-004) 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. 2. Any condition or laboratory abnormality that would make the subject, in the judgment of the investigator, unsuitable for the study. 3. Significant history of drug addiction (with the exception of nicotine dependence) or abuse (including alcohol, as defined in DSM-5 or in the opinion of the investigator) within the last two years prior to informed consent, or a positive urine drug screen for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at baseline. Prescription medication yielding a positive drug screen are acceptable except for tricyclic antidepressants. 4. Any known hypersensitivity to any of the excipients contained in the study drug formulation. |
1. Ongewenste voorvallen (AE's) uit de vorige studie (ANAVEX2-73-AD-004) die niet zijn verdwenen, matig of ernstig zijn, mogelijk verband houden met of gerelateerd zijn aan het onderzoeksmiddel en door de onderzoeker als een contra-indicatie worden beschouwd studiedeelname te verlengen. 2. Elke aandoening of laboratoriumafwijking die de proefpersoon, naar het oordeel van de onderzoeker, ongeschikt zou maken voor het onderzoek. 3. Significante voorgeschiedenis van drugsverslaving (met uitzondering van nicotineverslaving) of drugsmisbruik (inclusief alcohol, zoals gedefinieerd in DSM-5 of naar de mening van de onderzoeker) in de laatste twee jaar voorafgaand aan toestemming, of een positieve urine drugscreening op cocaïne, opioïde, fencyclidine (PCP), amfetamine of marihuana bij de baseline. Geneesmiddelen op recept die een positieve drugscreening opleveren, zijn acceptabel, behalve voor tricyclische antidepressiva. 4. Elke bekende overgevoeligheid voor de hulpstoffen in de formulering van het onderzoeksmiddel.
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E.5 End points |
E.5.1 | Primary end point(s) |
To continue assessing the safety and tolerability of ANAVEX2-73. Safety and Tolerability Measures: 1. Physical and neurological examination 2. Vital signs (heart rate, respiratory rate, systolic blood pressure [SBP], diastolic blood pressure [DBP], and oral body temperature) 3. Graded Adverse Events (AEs) according to common Terminology Criteria for Adverse Events (CTCAE) V4.0.3 4. 12-lead ECG 5. Clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) 6. Columbia-Suicide Severity Rating Scale (C-SSRS) 7. Documenting concomitant medications |
Continueren met het beoordelen van de veiligheid en verdraagbaarheid van ANAVEX2-73. Metingen voor veiligheid en verdraagbaarheid: • Lichamelijk onderzoek • Vitale functies (hartslag, ademhalingsfrequentie, systolische en diastolische bloeddruk, pulse oximetrie en orale lichaamstemperatuur • Gegradeerde AEs volgend de Terminology Criteria for Adverse Events (CTCAE) v4.0.3 • 12-lead ECG • Columbia-Suicide Severity Rating Scale (C-SSRS) • Laboratorium onderzoek (hematologie, stolling, klinische chemie inclusief lipiden panel en urine analyse) • Documentatie van gelijktijdig genomen medicatie
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Observation of P-tau blood level concentration • To determine whether ANAVEX2-73 modifies cognition, behavior, or QoL, according to the following standardized measures commonly used in AD: - Change from baseline to week 96 in ADAS-Cog - Change from baseline to week 96 in ADCS-ADL - Change from baseline to week 96 in MMSE - Change from baseline to week 96 in NPI-Q - Change from baseline to week 96 in ZBI - Change from baseline to week 96 in QoL-AD
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• Observeren van de P-tau bloedspiegel • Bepalen of ANAVEX2-73 cognitie, gedrag of QoL wijzigt, volgens aan de volgende gestandaardiseerde metingen die vaak worden gebruikt in AD: - Verandering vanaf baseline tot week 96 in ADAS-Cog - Verandering vanaf baseline tot week 96 in ADCS-ADL - Verandering vanaf baseline tot week 96 in MMSE - Verandering vanaf baseline tot week 96 in NPI-Q - Verandering vanaf baseline tot week 96 in ZBI - Verandering vanaf baseline tot week 96 in QoL-AD.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
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 | 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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Australia |
Canada |
Germany |
Netherlands |
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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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LVLS |
Laatste patiënt, laatste visite, |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 4 |