A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Parkinson’s Disease with Dementia Patients.

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2017-004335-36-ES
• Date of registration: 11/04/2018
• Prospective Registration: Yes
• Primary sponsor: Anavex Life Sciences Corp.
• Public title: A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Parkinson’s Disease with Dementia Patients.
• Scientific title: A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73 for Cognitive Impairment in Parkinson’s Disease with Dementia Patients. - A Phase II Study to Evaluate the Safety, Tolerability, and Efficacy of ANAVEX2-73
• Date of first enrolment: 04/07/2018
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004335-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Irene Mínguez Ardura
• Affiliation: Leon Research S.L.

• Name: Irene Mínguez Ardura
• Affiliation: Leon Research S.L.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of idiopathic Parkinson’s disease (PD) consistent with the UK Parkinson’s Disease Society Brain Bank diagnostic criteria.
2. Diagnosis of probable PD dementia (PDD) according to the Movement Disorder Society Task Force clinical diagnostic criteria.
3. Montreal Cognitive Assessment (MoCA) score of 13 to 23, inclusive, at Screening.
4. Male or female and aged = 50 years.
5. Caregivers and subjects (or legal representative) must understand and have signed approved informed consent.
6. Caregivers and subjects (or legal representative) must be able to understand study requirements and be willing to follow instructions.
7. 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.
8. 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.
9. 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.
10. Contraception:
o 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.
o 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.
Note: For men and women, acceptable methods of contraception include use of a condom with spermicide or use of oral, implantable or injectable contraceptives, or IUD, or a diaphragm with spermicide or diaphragm with condom.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
1. History of any significant neurologic or psychiatric disorder other than PD that can contribute to cognitive impairment.
2. 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.
3. Potential symptomatic causes of cognitive impairment including but not limited to
a. abnormal thyroid function test at screening (TSH)
b. abnormal B12 level at screening
c. MRI findings (by history) pointing to a potential symptomatic cause of cognitive dysfunction, including significant vascular changes, or communicating hydrocephalus.
4. Treatment with memantine or amantadine. If appropriate the drugs can be discontinued for a minimum of 4 weeks prior to randomization.
5. Use of over the counter (OTC) or prescription medication for sleep on 2 or more occasions per week (less than that is allowed).
6. History of depression as measured by Beck Depression Inventory score >17 at screening.
7. Treatment with any other investigational drug or device within 4 weeks prior to screening.
8. Smoking > 1 pack of cigarettes per day (as assessed for the 4 weeks prior to screening).
9. Women who are pregnant or lactating.
10. Known allergy or sensitivity to ANAVEX2-73 or any of its components.
11. 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.
12. Use of centrally acting anticholinergic drugs during the 4 weeks before randomization.
a. Medications used for overactive bladder will be allowed provided that the regimen has been stable 4 weeks prior to randomization.
13. Treatment with any dopamine receptor blocking medications with the exception of low dose quetiapine (=50 mg/day). Pimavanserin (=34 mg/day) will be allowed.
14. History of neurosurgical intervention (e.g., deep brain stimulation) for PD.
15. Unpredictable motor fluctuations that would interfere with administering cognitive assessments in the ON state.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cognition in Parkinson’s Disease with dementia

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: ANAVEX2-73
Pharmaceutical Form: Capsule
INN or Proposed INN: ANAVEX2-73
Current Sponsor code: ANAVEX2-73
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: ANAVEX2-73
Pharmaceutical Form: Capsule
INN or Proposed INN: ANAVEX2-73
Current Sponsor code: ANAVEX2-73
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: To assess the safety and tolerability of ANAVEX2-73 compared to placebo. To
assess the efficacy of ANAVEX2-73 in cognition compared to placebo.

Primary end point(s): Primary efficacy endpoint: 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.
Primary safety endpoint: Tolerability as determined by the number of subjects completing the study on active treatment versus placebo and proportion of subjects completing the study.

Secondary Objective: To evaluate the efficacy of ANAVEX2-73 in reducing Parkinsonian motor
symptoms in PDD patients compared to placebo.

Timepoint(s) of evaluation of this end point: Primary efficacy endpoint: 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.
Primary safety endpoint: Tolerability as determined by the number of subjects completing the study on active treatment versus placebo and proportion of subjects completing the study.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints: Change from Baseline to End of Treatment in Power of Attention as measured by CDR Power of Attention test and Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores).

Secondary end point(s): Secondary efficacy endpoints: Change from Baseline to End of Treatment in Power of Attention as measured by CDR Power of Attention test and Change from baseline to End of Treatment as measured by MDS-UPDRS Part III Total Score (Motor Scores).

Secondary ID(s)

ANAVEX2-73-PDD-001

Source(s) of Monetary Support

Anavex Life Sciences Corp.