This is a Phase II, randomized, placebo-controlled, double-blind, crossover study on the CNS and pharmacodynamic effects of clenbuterol (CST-103) co-administered with nadolol (CST-107) in 4 subject populations with Neurodegenerative Disorders.
Approximately 40 subjects with Parkinson's Disease (PD) with REM Sleep Behavior Disorder (RBD) and Depressive Symptoms, Mild Cognitive Impairment (MCI) with Depressive Symptoms, Dementia with Lewy Bodies (DLB) with Cognitive Fluctuations, and Parkinson's Disease Dementia (PDD) with Cognitive Fluctuations were to be enrolled in a 2 period, 2-way crossover design following study eligibility confirmation during the screening period. The number of subjects enrolled in each cohort could change as emerging data are reviewed from this and other studies. During each treatment period, subjects received daily doses of clenbuterol (CST-103) co-administered with nadolol (CST-107) or matching placebo for 14 days. Each treatment period was separated by a washout period of 14 days (+5-day window). All subjects completed clinical and pharmacodynamic assessments during each treatment period and PK blood samples were collected prior to, during and after study medication administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
41
clenbuterol (CST-103) and matching placebo orange capsules; nadolol (CST-107) and matching placebo white capsules
The University of Sydney
Sydney, New South Wales, Australia
Wesley Medical Research Ltd
Brisbane, Queensland, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
NZBRI
Christchurch, New Zealand
Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)
Faces with six different basic emotions (happiness, fear, anger, disgust, sadness, surprise) are briefly displayed on a screen and participants are required to indicate the expression of the face via a button-press. Cohort A only.
Time frame: Days 7 and 14 of each Treatment Period (Two 14-day periods)
Change From Baseline in Cognitive Fluctuations
Dementia Cognitive Fluctuation Scale (DCFS). Number of participants with improvement relative to screening. Cohort B only.
Time frame: Screening, Days 1 and 14 of each Treatment Period (Two 14-day periods)
Change From Baseline in CANTAB Cognitive Assessments
The CANTAB cognitive assessments consists of a series of interrelated computerized tests of memory, attention, and executive function, administered via a touch sensitive screen. This includes the immediate and delayed Verbal Recognition Memory (VRM) recall and recognition tests that measure the ability to encode and subsequently retrieve verbal information.
Time frame: Days 1, 7, 14 of each Treatment Period (Two 14-day periods)
Digital Wearable Device (BioStamp) - Sleeping Heart Rate
A wireless device that measures physical activity and sleep while at home.
Time frame: Screening, Days 1-14 of each Treatment Period (Two 14-day periods)
Digital Wearable Device (BioStamp) - Sleeping Heart Rate Variability (HRV)
A wireless device that measures physical activity and sleep while at home.
Time frame: Screening, Days 1-14 of each Treatment Period (Two 14-day periods)
Digital Wearable Device (BioStamp) - Sleeping Heart Rate Variability (HRV) - Root Mean Square of Successive Differences (RMSSD)
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MAC
Tankersley, Barnsley, United Kingdom
MAC
Blackpool, Lancashire, United Kingdom
MAC
Manchester, United Kingdom
A wireless device that measures physical activity and sleep while at home.
Time frame: Screening, Days 1-14 of each Treatment Period (Two 14-day periods)