A study to evaluate the safety and tolerability of IRL752 treatment in patients with Parkinson's disease dementia.

• Register: EUCTR
• Last refreshed on: 19 November 2018
• Main ID: EUCTR2017-001673-17-FI
• Date of registration: 29/08/2017
• Prospective Registration: Yes
• Primary sponsor: Integrative Research Laboratories AB
• Public title: A study to evaluate the safety and tolerability of IRL752 treatment in patients with Parkinson's disease dementia.
• Scientific title: A randomized, double-blind, placebo-controlled, multi-centre phase IIa study evaluating the safety and tolerability of IRL752 in patients with Parkinson's Disease Dementia
• Date of first enrolment: 03/10/2017
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001673-17
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Finland, Sweden

Contacts

• Name: CRST Oy
• Affiliation: Clinical Research Services Turku CRST Oy

• Name: CRST Oy
• Affiliation: Clinical Research Services Turku CRST Oy

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female 55-85 years of age.
2. Female patients must be of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulation hormone (FSH) 25-140 IE/L and estradiaol <200 pmol/L is confirmatory]).
3. Fertile male patients must be willing to use condom and refrain from donating sperm during the study and ensure that their fertile female partners are using contraceptive methods to prevent pregnancy .
4. Diagnosis of idiopathic Parkinson's disease, according to the UK Parkinson's disease Society Brain Bank criteria.
5. Diagnosis of PDD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV TR) criteria, with onset of symptoms of dementia at least two years following the first diagnosis of idiopathic PD.
6. Mini Mental State Examination (MMSE) score of =12 and = 26 at screening.
7. On a stable regimen of anti-Parkinson's medications for at least 30 days prior to screening (Selegelin not allowed), and willing to continue the same doses and regimens during study participation.
8. Availability of a responsible caregiver at least four days per week.
9. Able to cooperate and participate in study related procedures.
10. Written informed consent for participation in the study given by the patient.
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 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion criteria:
1. An advanced, severe, or unstable disease of any type that may interfere with the primary and secondary variable evaluations.
2. A score of 5 (wheelchair bound or bedridden) in the "on"-state on the Modified Hoehn and Yahr Staging (UPDRS Part 5).
3. A current diagnosis of any primary neurodegenerative disorder other than idiopathic PD.
4. A current diagnosis of any treatable dementia (hypothyroidism, syphilis, vitamin B12 or folate deficiency) that is verified by the investigator to be the cause of dementia.
5. A current diagnosis of probably vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria.
6. A current diagnosis of a major depressive episode according to DSM-IV criteria.
7. A history of stereotaxic brain surgery for PD.
8. Any history of a clinically relevant heart condition, including prolonged QTc (>450 ms), clinically relevant cardiac arrhythmias, any repolarisation deficits or any other clinically significant abnormal ECG as judged by the Investigator.
9. Severe or ongoing unstable medical condition including a history of poorly controlled diabetes; obesity associated with metabolic syndrome; uncontrolled hypertension; cerebrovascular disease, or any form of clinically significant cardiac disease; symptomatic orthostatic hypotension; hepatic disease; renal failure, history of abnormal renal function; or seizures.
10. Creatinine clearance <45 ml/min (calculated according to the Cockcroft-Gault formula).
11. History of severe allergy/hypersensitivity or severe on-going allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL752.
12. Treatment with Warfarin within three (3) months before study treatment.
13. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment with less than three months between administration of last dose and first dose of IMP in this study.
14. Current or history of alcohol abuse and/or use of drugs of abuse.
15. Any planned major surgery within the duration of the study.
16. Any other condition or symptoms preventing the patient from entering the study, according to the Investigator’s judgement.


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

Health Condition(s) or Problem(s) studied

Dementia in Parkinson's disease
MedDRA version: 20.0 Level: LLT Classification code 10012284 Term: Dementia due to Parkinson's disease System Organ Class: 100000014717

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

Intervention(s)

Product Name: IRL752
Pharmaceutical Form: Capsule
INN or Proposed INN: IRL752
CAS Number: 1227638-29-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Frequency, seriousness and intensity of AEs – at visit 2-8 and Follow-up.
Physical examination – at visit 8 and Follow-up.
ECG recordings – at visit 6, 7 and Follow-up.
Vital signs (blood pressure and pulse) – at visit 6,8 and Follow-up.
Safety laboratory measurements – at visit 8 and Follow-up.

Secondary Objective: 1. Evaluate the effects of IRL752 on symptoms of Parkinson's disease
(PD) assessed with UPDRS part 1-4, as compared to placebo.
2. Evaluate the effects of IRL752 on postural control and walking speed
assessed with TUG test, as compared to placebo.
3. Evaluate the effects of IRL752 on freezing of gait assessed with the
FOGQ, as compared to placebo.
4. Evaluate the effects of IRL752 on cognitive functions assessed with
the CANTAB, as compared to placebo.
5. Evaluate the effects of IRL752 on neuropsychiatric symptoms
assessed with NPI-12, as compared to placebo.
6. Evaluate the effects of IRL752 on global function assessed with
CIBIC-Plus, as compared to placebo.
7. Evaluate the effects of IRL752 on EEG pattern changes as compared to
placebo.
8. Examine the exposure of IRL752 in patients with PDD.

Main Objective: The primary objective of the study is to evaluate the safety and
tolerability of IRL752 after repeated dosing in patients with Parkinson's
Disease Dementia (PDD).

Primary end point(s): The primary evaluation parameters are:
Frequency, seriousness and intensity of AEs
Physical examination
ECG recordings
Vital signs (blood pressure and pulse)
Safety laboratory measurements

Secondary Outcome(s)

Secondary end point(s): The secondary evaluation parameters are:
Change in UPDRS Part 1-4 scores from baseline to end of treatment.
Change in TUG test from baseline to end of treatment.
Change in FOGQ score from baseline to end of treatment.
Change in CANTAB performance from baseline to end of treatment,
including:
- Motor Screening Task
- Reaction time
- Spatial Working Memory Task
- One Touch Stockings of Cambridge
Change in NPI-12 scores from baseline (screening) to end of treatment.
CIBIC-Plus score at end of treatment.
Change in resting state EEG pattern from baseline to end of treatment.
Plasma concentrations of IRL752.

Timepoint(s) of evaluation of this end point: Change in UPDRS Part 1-4 scores – at visit 7.
Change in TUG test – at visit 7.
Change in FOGQ score – at visit 7.
Change in CANTAB performance – at visit 7.
Change in NPI-12 scores – at visit 8.
CIBIC-Plus score – at visit 8.
Change in resting state EEG pattern – at visit 7.
Plasma concentrations of IRL752 – at visit 2, 6 and 7.

Secondary ID(s)

2017-001673-17-SE

IRL752C002

Source(s) of Monetary Support

Integrative Research Laboratories AB