| Eligibility |
Inclusion Criteria:
1. Written informed consent (IC) obtained before any study assessments are performed.
2. Sufficient command of the Finnish language to be able to understand the subject
information and to communicate with the study personnel.
3. Males and females over 18 years of age.
4. Body mass index (BMI) between 18-30 kg/m2.
5. Idiopathic normal pressure hydrocephalus.
6. Shunt surgery with cerebroventricular catheter placed at least 3 months earlier.
7. Good general health, based on medical history, physical examination and laboratory
assessments.
8. Adequate mental status to give informed consent as assessed by the investigator and
using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
neuropsychological battery.
9. Female participants of child-bearing potential and male participants with female
partners of child-bearing potential must adhere to a highly effective form of
contraception (listed in Section 4.6) from the first study treatment administration
until 1 month after the EoS visit.
Exclusion Criteria:
1. Predicted poor compliance with study procedures, restrictions and requirements.
2. Vulnerable subjects (i.e. persons under any administrative or legal supervision).
3. Veins unsuitable for repeated venipuncture or cannulation
4. Evidence of other current clinically significant cardiovascular, renal, hepatic,
haematological, gastrointestinal, pulmonary, metabolicendocrine, neurological,
urogenital or psychiatric disease than iNPH, as judged by the investigator.
5. Type 1 diabetes mellitus.
6. Diagnosis of cancer for which the subject is currently being treated, or for which
there is evidence of active disease. Subjects with local prostate cancer or local
dermatological tumours, such as basal or squamous cell carcinoma, may be included.
7. Susceptibility to severe allergic reactions, e.g. history of anaphylactic shock due to
any reason.
8. Use of medications impacting the metabolism of dopamine, such as other COMT inhibitors
(e.g. entacapone), levodopa and monoamine oxidase (MAO) inhibitors (e.g. rasagiline,
selegiline), within 4 weeks before the first study drug administration.
9. Any clinically significant abnormalities in screening laboratory test results, vital
signs or physical examination findings that might influence the results of the study
or cause a health risk for the subject if he/she takes part in the study.
10. Any clinically significant 12-lead ECG abnormality, such as QTcF > 450 ms, after 10
min rest in supine position at the screening visit.
11. Heart rate (HR) < 50 bpm or > 90 bpm, systolic blood pressure (BP) < 90 mmHg or > 160
mmHg, or diastolic BP < 50 mmHg or > 100 mmHg in supine or seated position after 10
min rest at the screening visit.
12. Positive serology to human immunodeficiency virus antibodies (HIVAgAb), hepatitis C
virus antibodies (HCVAb) or hepatitis B surface antigen (HBsAg).
13. History of alcohol or drug abuse within the last 5 years, or current regular use of
illicit drugs or excessive use of alcohol (regular alcohol drinking of more than 24
units/week for males or 14 units/week for females), or positive breath test for
alcohol or positive urine test for drugs of abuse at screening or prior to the first
IMP administration.
14. Inability to refrain from consuming caffeine-containing beverages during the stay in
the unit.
15. Current use of nicotine-containing products, more than 5 cigarettes or equivalent/day,
or inability to refrain from using nicotine-containing products during the stay at the
study centre.
16. Pregnant or lactating females.
17. Participation in any other clinical drug study within 2 months before the first IMP
administration of this study.
18. Blood donation or loss of significant amount of blood within 2 months prior to the
screening visit.
19. Employee or first-degree relative of an employee of the contract research organization
(CRST) or Orion.
20. Any other condition that in the opinion of the investigator might interfere with the
evaluation of the study results or constitute a health risk for the subject.
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