A study of ORM-12741 on cognitive and behavioural symptoms such e.g. memory, orientation, learning in patients with Alzheimer’s disease (form of dementia)

• Register: EUCTR
• Last refreshed on: 19 November 2012
• Main ID: EUCTR2010-022922-34-FI
• Date of registration: 23/12/2010
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: A study of ORM-12741 on cognitive and behavioural symptoms such e.g. memory, orientation, learning in patients with Alzheimer’s disease (form of dementia)
• Scientific title: Safety and efficacy of ORM-12741 on cognitive and behavioural symptoms in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, parallel group, multicentre study of 12 weeks - ALPO
• Date of first enrolment: 01/03/2011
• Target sample size: 99
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022922-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes 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

Countries of recruitment

Finland, Spain

Contacts

• Name: Jutta Hänninen
• Affiliation: Orion Corporation Orion Pharma

• Name: Jutta Hänninen
• Affiliation: Orion Corporation Orion Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female patients with diagnosis of probable AD, written informed consent (IC) obtained from the subject and/or his/her caregiver. The subject must have a history of progressive cognitive deterioration, brain imaging consistent with AD, at least a mild level of behavioural symptoms present with a neuropsychiatric inventory (NPI) score > 15, mini-mental state examination (MMSE) score 12-21 at screening visit and be treated with donepezil, rivastigmine or galantamine for at least 3 months. The subject must be 55-90 years of age and fulfil all of the inclusion criteria and none of the exclusion criteria.
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 99
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 99

Exclusion criteria:
1. Any other type of dementia than AD.
2. Modified Hachinski Ischemia Score > 4.
4. Use of antipsychotics within 2 months prior to screening (even for sleep).
5. Use of benzodiazepines, other than short acting sleep medication, for night at a maximum of 3 nights/week, within 2 months prior to screening.
6. Use of any anticholinergic medication within 2 months prior to screening (including those used to treat overactive bladder and tricyclic antidepressants).
7. Changes in antidepressant dosing during the last 2 months prior to the screening.
8. Current use of other psychotropic agents, like antiepileptics or opioid analgesics
9. Myocardial infarction within the past 2 years.
10. Current or history of malignancy within the past 5 year.
11. Suicidal ideation in the 6 months before screening or current suicide risk based on the Columbia-Suicide Severity Rating Scale (C-SSRS) (items 4 and 5 exclusionary) or current risk of suicide based on the investigator’s judgement.
12. Subjects with known or suspected history of alcoholism or drug abuse (within the past 5 years).
13. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the patient if he/she takes part in the study.
14. Specific findings in MRI that might in the opinion of the investigator affect cognitive function such as cortical infarct, micro-haemorrhage, or silent lacuna (= 1 cm) in a region known to affect cognition such as the hippocampus of either hemisphere, the head of the left caudate, or the dorsomedial region of the left thalamus. With the exception of neuroanatomical areas defined, a maximum of one “clinically silent” lacunar infarct is permitted provided the maximal diameter in any dimension is = 1 cm detected on both T1 and T2 weighted MRI images or observed on CT scan images. Multiple white matter lesions consistent with leukoaraiosis are not exclusionary in an otherwise eligible subject.
15. Supine HR > 100 bpm after a 5-minute rest at screening visit.
16. Supine systolic BP (SPB) > 160 or diastolic BP (DPB) > 100 mmHg after a 5-minute rest at screening visit.
17. Symptomatic orthostatic hypotension at screening visit.
18. QTc-Fridericia (QTcF) repeatedly > 450 ms in males or > 470 ms in females at screening visit.
19. Abnormal thyroid-stimulating hormone (TSH), vitamin B12 or folate serum levels at screening (which can not be corrected with substitute therapy).
20. Any other abnormal value in laboratory tests, vital signs or ECG which may in the opinion of the investigator interfere with the interpretation of the study results (e.g. affect cognition) or cause a health risk for the patient if he/she takes part in the study.
21. Female patients of childbearing potential (i.e. menstruating or less than 2 years postmenopausal).
22. Patients with pre-planned elective surgery.
23. Known hypersensitivity to the active substance or to any of the excipients of the study drugs.
24. Blood donation or loss of significant amount of blood within 60 days prior to the screening.
25. Participation in a drug study within 60 days prior to the screening.
26. Previous AD immunotherapy treatment.
27. Patient cannot complete the Cognitive Drug Research Ltd. (CDR) cognitive test battery despite having undergone 2 training

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

Health Condition(s) or Problem(s) studied

Alzheimer’s disease (AD)
MedDRA version: 14.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Intervention(s)

Product Name: ORM-12741
Product Code: ORM-12741
Pharmaceutical Form: Capsule, hard
Current Sponsor code: ORM-12741
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: ORM-12741
Product Code: ORM-12741
Pharmaceutical Form: Capsule, hard
Current Sponsor code: ORM-12741
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Efficacy variables:
The following cognitive tests will be assessed: the Cognitive Drug Research Ltd. (CDR) cognitive test battery, the Controlled Oral Word Association Test (COWAT) and the Category Fluency Test (CFT).
Safety variables:
Safety will be assessed by adverse events (AEs), vital signs, 12-lead electrocardiogram (ECG), physical examination and laboratory safety assessments. Suicidality will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).

Main Objective: The primary objectives of the study are to evaluate the safety and tolerability of ORM-12741, and the efficacy of ORM-12741 on cognitive symptoms in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase (AChE) inhibitor therapy.

Secondary Objective: The secondary objectives are to evaluate the efficacy of ORM-12741 on behavioural symptoms, and plasma trough concentrations of ORM-12741 in patients with AD receiving AChE inhibitor therapy, and to evaluate the effects of ORM-12741 on plasma trough concentrations of the AChE inhibitors.

Timepoint(s) of evaluation of this end point: The CDR cognitive test will be assessed at screening and baseline. At week 1, 2, 4, 8 and 12 - 1 hour after investigational medicinal product (IMP) administration.
COWAT and CFT will be assessed at baseline and at week 1, 2, 4, 8 and 12 visits.

Secondary Outcome(s)

Secondary end point(s): Efficacy:
The following behavioural and psychological symptom tests will be assessed: the NPI and the Cornell Scale for Depression in Dementia (CSDD). In addition, the Cognitive Failures Questionnaire (CFQ) and the overall change in subject’s clinical condition by Clinical Global Impression of Change (CGI-C) will be assessed.
Pharmacokinetic (PK) variables:
Plasma concentrations of ORM-12741, ORM-13720, ORM-13859, ORM-13861, donepezile, galantamine and rivastigmine will be tabulated.
Pharmacogenetic (PG) variables:
All subjects participating in this study will provide a blood sample for extraction of DNA to determine the carrier status for the genes (markers) that have been associated with behavioural and psychological symptoms in AD, or affect the target receptor, and may predict the subject’s response to the study treatment. An additional blood sample for DNA extraction will be taken from those subjects who agree to take part in the optional study-related exploratory PG study.
Sample collection for exploratory studies:
Blood samples will be collected for metabolomics studies to allow possible exploratory studies related to the pharmacokinetics, pharmacodynamics, or safety of ORM-12741, its metabolites or AChE inhibitor treatments.

Timepoint(s) of evaluation of this end point: NPI behavioural test will be performed at screening, baseline and at week 4 and 12 visits.
CSDD and CGI-C test will be performed at baseline and at week 4 and 12 visits.
CFQ assessed at baseline and week 12 visit.
PK sampling for determination of ORM-12741, ORM-13720, ORM-13859 and ORM-13861 and AChEI is taken before the morning dose of the IMP on day 1 and at week 1, 2, 4, 8 and 12 visits

Secondary ID(s)

3098006

Source(s) of Monetary Support

Orion Corporation Orion Pharma