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

NCT04739423 | Completed Phase 2 Results

• 1 other identifier: CST103/CST107-CLIN-011
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 7

Brief Summary

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.

Conditions

Mild Cognitive Impairment, Lewy Body Dementia, Parkinson's Disease Rapid Eye Movement Sleep Behavior Disorder, Parkinson's Disease Dementia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Screening, Days 1 and 14 of each Treatment Period (Two 14-day periods)

Secondary Outcomes (4)

• Change From Baseline in CANTAB Cognitive Assessments

  Days 1, 7, 14 of each Treatment Period (Two 14-day periods)

• Digital Wearable Device (BioStamp) - Sleeping Heart Rate

  Screening, Days 1-14 of each Treatment Period (Two 14-day periods)

• Digital Wearable Device (BioStamp) - Sleeping Heart Rate Variability (HRV)

  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)

  Screening, Days 1-14 of each Treatment Period (Two 14-day periods)

Study Arms (2)

CST-103/CST-107 to Placebo

EXPERIMENTAL

Subjects will receive daily doses of CST-103 co-administered with CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by matching placebo for CST-103 and matching placebo for CST-107 for 14 days.

Drug: clenbuterol (CST-103), nadolol (CST-107), matching placebo

Placebo to CST-103/CST-107

EXPERIMENTAL

Subjects will receive daily doses of matching placebo for CST-103 co-administered with matching placebo for CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by daily doses of CST-103 co-administered with CST-107 for 14 days.

Drug: clenbuterol (CST-103), nadolol (CST-107), matching placebo

Interventions

clenbuterol (CST-103), nadolol (CST-107), matching placebo DRUG

clenbuterol (CST-103) and matching placebo orange capsules; nadolol (CST-107) and matching placebo white capsules

CST-103/CST-107 to Placebo; Placebo to CST-103/CST-107

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy.
• Pulmonary disease, including asthma if requiring the use of a β2-Adrenergic bronchodilator, or evidence of clinically significant moderate or severe pulmonary symptoms.
• Clinical signs indicating syndromes such as corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, or Babinski sign.
• Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or meeting DSM-IV diagnostic criteria for psychotic disorders.
• Evidence of any significant clinical disorder or laboratory finding (or in the case of potassium levels below normal range) that renders the participant unsuitable for receiving an investigational drug.
• History of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
• Any clinically significant illness or disease as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening.
• Clinically significant abnormalities of ECG, including QTcF \> 450 ms, for males and QTcF \> 470 ms for females, and/or HR \< 50 beats per minute, or evidence of clinically significant bundle branch blocks, as indicated by 12-lead ECG.
• Calculated creatinine clearance of ≤70 mL/min according to the Cockcroft-Gault equation.
• Current use of any prohibited prescription medication (high-dose aspirin, paracetamol or levodopa, β-AR agonists or β-AR blockers, hypnotics or benzodiazepines other than clonazepam, monoamine oxidase inhibitors, opioids ), over-the-counter medication, or herbal supplements/products.
• Prior treatment with any investigational drug ≤90 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrollment in any other study treatment or disease study, except for observational studies.
• Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse.
• Active suicidal ideation within 3 months prior to study Screening.
• Positive screening test for hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] at Screening).
• Positive screening test for human immunodeficiency virus (HIV).

Sponsors & Collaborators

• CuraSen Therapeutics, Inc.: lead

Study Sites (7)

The University of Sydney

Sydney, New South Wales, 2006, Australia

Location

Wesley Medical Research Ltd

Brisbane, Queensland, QLD 4066, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

NZBRI

Christchurch, 8011, New Zealand

Location

MAC

Tankersley, Barnsley, S75 3DL, United Kingdom

Location

MAC

Blackpool, Lancashire, FY2 0JH, United Kingdom

Location

MAC

Manchester, M13 9NQ, United Kingdom

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Lewy Body Disease

Interventions

Clenbuterol; Nadolol

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenoxypropanolamines; Propanolamines; Propanols

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: CuraSen Therapeutics, Inc

clinicaltrials@curasen.com

+1 650 475 2842

Study Officials

• Chief Medical Officer

  CuraSen Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two 14-day periods, 2-way crossover design

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 4, 2021
• Study Start: June 28, 2021
• Primary Completion: July 4, 2022
• Study Completion: August 31, 2022
• Last Updated: December 2, 2024
• Results First Posted: December 2, 2024

Record last verified: 2024-10

Locations

AU (3); GB (3); NZ (1)