ANAVEX2-73 Study in Parkinson's Disease Dementia

• Sponsor: Anavex Life Sciences Corp.
• Collaborator: Anavex Germany GmbH
• Information provided by (Responsible Party): Anavex Life Sciences Corp.

Study Description

Brief Summary:

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients with Parkinson's Disease with Dementia (PDD)

Condition or disease	Intervention/treatment	Phase
Parkinsons Disease With Dementia	Drug: High dose ANAVEX2-73; Drug: Mid dose ANAVEX2-73; Drug: Placebo oral capsule	Phase 2

Detailed Description:

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, three-arm, 14-week study in PD patients with dementia. The study includes a 2 week Screening / Baseline Observation Period and a 14-week Treatment Period (including a 2 week Titration Period), and a 2-week Safety Follow-Up Period

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Patients With Parkinson's Disease With Dementia
Actual Study Start Date :	July 9, 2018
Estimated Primary Completion Date :	November 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: High dose ANAVEX2-73; High dose ANAVEX2-73	Drug: High dose ANAVEX2-73; Active oral capsule
Experimental: Mid dose ANAVEX2-73; Mid dose ANAVEX2-73	Drug: Mid dose ANAVEX2-73; Active oral capsule
Placebo Comparator: Placebo oral capsule; Placebo oral capsule	Drug: Placebo oral capsule; Placebo oral capsule

Outcome Measures

Primary Outcome Measures :

1. Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention [ Time Frame: 14 weeks ]
   Change from Baseline to End of Treatment in Continuity of Attention as measured by Cognitive Drug Research (CDR) Computerized Assessment System Continuity of Attention test
2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 14 weeks ]
   Assess the safety and tolerability of ANAVEX2-73 compared to placebo

Secondary Outcome Measures :

1. MDS-UPDRS Part III Total Score (Motor Scores) [ Time Frame: 14 weeks ]
   Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores)
2. SDS-CL-25 [ Time Frame: 14 weeks ]
   Incidence of sleep disorders symptoms (SDS-CL-25)

Eligibility Criteria

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Ages Eligible for Study:	50 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson's disease (PD) consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria.
• Diagnosis of probable PD dementia (PDD) according to the Movement Disorder Society Task Force clinical diagnostic criteria.
• Montreal Cognitive Assessment (MoCA) score of 13 to 23, inclusive, at Screening.
• Male or female and aged ≥ 50 years.
• Caregivers and subjects (or legal representative) must understand and have signed approved informed consent.
• Caregivers and subjects (or legal representative) must be able to understand study requirements and be willing to follow instructions.
• Stable regimen of anti-Parkinson's disease medications (including levodopa, dopamine agonists, MAO-B inhibitors, or the COMT inhibitor entacapone), which has been stable for at least 4 weeks prior to Baseline.
• Treatment with cholinesterase inhibitor (rivastigmine, donepezil and galantamine (Exelon®, Aricept®, or Reminyl®) will be permitted, provided the dose has been stable for a minimum of 8 weeks prior to randomization.
• Subjects with history of depression on antidepressant medications will be allowed if depression is controlled and they have been on a stable daily dose of the antidepressant for ≥8 weeks before Baseline.

• Contraception:

  • Women of childbearing potential must use an acceptable method of contraception starting 4 weeks prior to study drug administration and for a minimum of 4 weeks after study completion. Otherwise, women must be postmenopausal (at least one year absence of vaginal bleeding or spotting) as confirmed by FSH greater than or equal to 40 mIU/mL or 40 IU/L or be surgically sterile.
  • Men with a potentially fertile partner must have had a vasectomy or be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation.

Exclusion Criteria:

• History of any significant neurologic or psychiatric disorder other than PD that can contribute to cognitive impairment.
• Any other condition or clinically significant abnormal findings like severe co-morbidities e.g. history of stroke, poor kidney or liver function on the physical or neurological examination, medical and psychiatric history, at screening or at baseline that, in the opinion of the Investigator, would make the subject unsuitable for the study.

• Potential symptomatic causes of cognitive impairment including but not limited to

  1. abnormal thyroid function test at screening (TSH)
  2. abnormal B12 level at screening
  3. MRI findings (by history) pointing to a potential symptomatic cause of cognitive dysfunction, including significant vascular changes, or communicating hydrocephalus.
• Treatment with memantine or amantadine. If appropriate the drugs can be discontinued for a minimum of 4 weeks prior to randomization.
• Use of over the counter (OTC) or prescription medication for sleep on 2 or more occasions per week (less than that is allowed).
• History of depression as measured by Beck Depression Inventory score >17 at screening.
• Treatment with any other investigational drug or device within 4 weeks prior to screening.
• Smoking > 1 pack of cigarettes per day (as assessed for the 4 weeks prior to screening).
• Women who are pregnant or lactating.
• Known allergy or sensitivity to ANAVEX2-73 or any of its components.
• Suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS) of type 4 or type 5, or any suicidal behavior, in the past 6 months. Type 4 indicates active suicidal ideation with some intent to act, without a specific plan. Type 5 indicates active suicidal ideation with a specific plan and intent.
• Use of centrally acting anticholinergic drugs during the 4 weeks before randomization.
• Medications used for overactive bladder will be allowed provided that the regimen has been stable 4 weeks prior to randomization.
• Treatment with any dopamine receptor blocking medications with the exception of low dose quetiapine (≤50 mg/day). Pimavanserin (≤34 mg/day) will be allowed.
• History of neurosurgical intervention (e.g., deep brain stimulation) for PD.
• Unpredictable motor fluctuations that would interfere with administering cognitive assessments in the ON state.

Contacts and Locations

Contacts

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Contact: Study Director	844-689-3939	pdd@anavex.com

Locations

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Spain
Hospital de la Santa Creu i Sant Pau	Recruiting
Barcelona, Spain
Contact: Jaime Kulisevsky
Hospital Universitario Vall d'Hebron	Recruiting
Barcelona, Spain
Contact: Jorge Hernández Vara
Hospital Universitario de Burgos	Recruiting
Burgos, Spain
Contact: Esther Cubo
Hospital del Henares	Recruiting
Coslada, Spain
Contact: Elena Toribio
Hospital General Universitario de Elche	Recruiting
Elche, Spain
Contact: Eric Freire Álvarez
Hospital Arquitecto Marcide	Recruiting
Ferrol, Spain
Contact: Diego Santos García
Hospital Santa Caterina	Recruiting
Girona, Spain
Contact: Berta Solano
Clinica Ruber Internacional	Recruiting
Madrid, Spain
Contact: Monica Kurtis
Clínica Universidad de Navarra (CUN) - Sede Madrid- Servicio de Neurología -	Recruiting
Madrid, Spain
Contact: Antonio Martín Bastida
Hospital Clínico San Carlos	Recruiting
Madrid, Spain
Contact: Rocío García Ramos
Hospital de La Princesa	Recruiting
Madrid, Spain
Contact: Lydia López
Hospital General Universitario Gregorio Marañón	Recruiting
Madrid, Spain
Contact: Francisco Grandas
Hospital Infanta Leónor	Recruiting
Madrid, Spain
Contact: Alberto Esquivel
Hospital HM Puerta del Sur	Recruiting
Móstoles, Spain
Contact: Carmen Gasca-Salas
Hospital Universitario Central de Asturias (HUCA)	Recruiting
Oviedo, Spain
Contact: Marta Blázquez Estrada
Clínica Universidad de Navarra (CUN)	Recruiting
Pamplona, Spain
Contact: María Cruz Rodríguez Oroz
Hospital de Santiago de Compostela	Recruiting
Santiago de Compostela, Spain
Contact: Angel Sesar
Hospital Universitario Virgen del Rocío	Recruiting
Sevilla, Spain
Contact: Pablo Mir

Sponsors and Collaborators

Anavex Life Sciences Corp.

Anavex Germany GmbH

More Information

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Responsible Party:	Anavex Life Sciences Corp.
ClinicalTrials.gov Identifier:	NCT03774459 History of Changes
Other Study ID Numbers:	ANAVEX2-73-PDD-001
First Posted:	December 13, 2018
Last Update Posted:	December 13, 2018
Last Verified:	December 2018

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Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

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Parkinson Disease; Dementia; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases	Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders