SRC Inhibition as a Potential Target for Parkinson's Disease Psychosis

• Status: Unknown status
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Parkinson's disease is often characterised by movement symptoms such as rigidity and bradykinesia, however, there are a number of non-motor symptoms that can have a significant impact on quality of life. One of the most common non-motor symptoms of Parkinson's disease is visual hallucinations (where someone sees things that don't exist outside their mind). . Recent findings led to the approval of a drug called Pimavanserin as a treatment for PD psychosis in the USA. Based on other recent studies, we believe that Saracatinib, a drug that interacts within the same system as Pimavanserin, is a potential treatment for PD psychosis. Saracatinib has shown to reduce the intensity of the psychedelic effect induced by psilocybin (a naturally occurring psychedelic found in psilocybe mushrooms) and attenuate social cognition and brain changes in healthy volunteers. The aim of this study is to test the effects of 14 days dosing of saracatinib or placebo on 30 volunteers with PD psychosis. We aim to to use neuroimaging combined with psychopharmacology to provide evidence that a putative new treatment approach can modulate abnormal visual cortex activation in patients with PD psychosis. If positive, this proof of mechanism study would provide a strong platform to pursue symptom modification studies with Saracatinib.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: King's College London
• Collaborators: AstraZeneca; King's College Hospital NHS Trust
• Treatments: Saracatinib

Criteria

Inclusion Criteria:

• Understand the study procedures and agree to participate by providing written informed consent.

• Have a confirmed diagnosis of Parkinson's disease using internationally accepted UK brain bank criteria.

• Be male or female

• Be right handed

• Aged 40 years or over

• Be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12 lead ECG and vital signs measurements performed at screening and prior to administration of the initial dose of study drug.

• Have a score of at least 22 on the Montreal Cognitive Assessment (MoCA).

• Have a diagnosis of idiopathic PD with moderate severity

• Have a combined score of at least 6 or an individual score of at least 4 on the neuropsychiatric inventory (NPI [20]) 23 items A (delusions) and/or B (hallucinations).

Exclusion Criteria:

• Is a female of child bearing potential

• Is currently taking anticholinergic medication

• Is currently taking any medication known to be a moderate or potent CYP3A4 inducer or inhibitor.

• Has an ongoing disability, medical or neurological history, cognitive impairment, or conditions that in the opinion of the investigator may interfere with study conduct or clinical assessments.

• Refuses to be withdrawn from quetiapine (see section 4.7).

• Has a family history of psychosis in a first degree relative

• Has poor peripheral arterial/venous access or recent wrist trauma that will restrict ability to gain venous access.

• Is currently using prescription or non-prescription drugs and herbal supplements, which are deemed to affect the integrity of the study, within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication. As an exception, paracetamol or acetaminophen may be used at doses of 1 g/day.

• Has a history of sensitivity to any of the study medications or any of the excipient constituents.

• Has a history of febrile illness within 5 days prior to the first dose

• Has a hairstyle which would affect EEG recording.

• Has any condition possibly affecting drug absorption (eg, gastrectomy).

• Has a history of regular alcohol consumption exceeding 14 units/week (6 glasses of 13.0% wine (175ml), 6 pints of 4.0% lager or ale (568ml), 5 pints of 4.5% cider (568 ml) or 14 glasses of 10.0% spirits (25ml)) within 6 months of screening.

• Uses tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.

• Uses caffeine containing products of the equivalence of 5 cups of regular filter coffee per day

• Has a positive urine drug screen on or after the screening visit during their active involvement in the study for opiates, methadone, cocaine, amphetamines (including MDMA), barbiturates, benzodiazepines and cannabinoids.

• Is unwilling or unable to comply with the Lifestyle guidelines.

• Has, in the opinion of the investigator, has any medical or psychological condition or social circumstances which would impair their ability to participate reliably in the study, or who may increase the risk to themselves or others by participating.

• Is male and is unwilling to follow the contraception guidance or has a female partner of child bearing potential who is unwilling to follow the contraception guidance throughout the study.

• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN)

• Total bilirubin > 1.25 x ULN

• Known congenital long QT syndrome

• Baseline resting QTcF > 470ms on 12 lead ECG

• Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening

• Known to have tested positive for human immunodeficiency virus.

• Participation in another clinical study with an investigational product administered in the last 3 months

• Below the lower limit of normal Hb, total WBC and neutrophils on blood counts as per the reference ranges of the laboratory conducting the tests.