A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders

Inclusion Criteria

• •Subjects with PD:
• •Male or female subjects ≥ 40 and ≤ 80 years of age, at time of informed consent.
• •Diagnosed with Parkinson's Disease, as defined by the United Kingdom Parkinson Disease Brain Bank criteria, associated with REM sleep behavior disorder (PD)
• •Modified Hoehn \& Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening.
• •Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 28.
• •Subjects with MCI:
• •Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent.
• •Meet the criteria for amnestic Mild Cognitive Impairment (MCI) as per the National Institute on Aging-Alzheimer's Association core clinical criteria.
• •Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26.
• •No dementia according to the International Classifications of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV.
• •Memory complaint reported by the subject or his/her partner, family member or caregiver.
• •Score of greater than or equal to one standard deviation below age and educational norms in the Digit Symbol Substitution Test (DSST) during Screening.
• •Cognitive decline not primarily caused by vascular, traumatic, or medical problems.
• •Subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD):
• •Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent.
• •Diagnosis of dementia associated with Dementia with Lewy Bodies or Parkinson's disease (PDD).
• •Documented cognitive fluctuations endorsed on the Dementia Cognitive Fluctuation Scale (DCFS) with a combined score of ≥8 in items 4, 11, 12 and 14.
• •Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26.
• •Have informant or caregiver throughout the study who will submit written consent to cooperate with this study, who routinely accompanies and/or stays with subject 12 hours or more a week, assists with treatment compliance, provides assessments and is able to escort the subject on required visits to study institution.
• •Modified Hoehn \& Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening.
• •Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI.
• •For ALL Subjects:
• •Unless confirmed to be azoospermic (vasectomized or secondary to medical cause), males must agree to use a male condom from Day 1 throughout the study when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant.
• •Females of childbearing potential (i.e., not postmenopausal or surgically sterile) who have a male partner must have a negative serum pregnancy test result and must agree to one of the following from start of Screening through 30 days after the last study medication administration: use a reliable method of birth control, or monogamous relationship with a male partner of confirmed sterility, or practice complete abstinence.
• •Females of non-childbearing potential may be enrolled if it is documented that they are postmenopausal.
• •Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35 kg/m2, inclusive at Screening.
• •Stable medical conditions for 3 months prior to Screening visit (e.g., controlled hypertension, dyslipidemia).
• •Willing to follow the protocol requirements and comply with protocol restrictions.
• •Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative.