Patients with Mild Cognitive Impairment or Parkinson’s Disease MedDRA version: 21.1 Level: LLT Classification code 10009846 Term: Cognitive impairment System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Spiropent
Product Name: Clenbuterol HCl
Product Code: CST-103
Pharmaceutical Form: Capsule
INN or Proposed INN: CLENBUTEROL HYDROCHLORIDE
CAS Number: 21898-19-1
Current Sponsor code: CST-1
Sponsors
CuraSen Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A – healthy subjects A subject will be considered eligible for enrollment if all of the following criteria are met: 1. Males and females aged 40-75 years (inclusive) at the time of informed consent 2. Body weight = 50 kg and body mass index (BMI) between 18 and 32 kg/m2, inclusive at Screening 3. 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. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a condom during each episode of penile-vaginal penetration until after the End of Study Visit 4. 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 30 days prior to Day 1 through 30 days after the last study medication administration: a. use a reliable method of birth control, or b. monogamous relationship with a male partner of confirmed sterility, or c. practice complete abstinence 5. Females of non-childbearing potential may be enrolled if it is documented that they are postmenopausal or have undergone surgical sterilization 6. Subject is free from clinically significant illness or disease as determined by medical and surgical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory assessments conducted at Screening 7. Able to speak, read and understand English 8. Able to understand and sign the written informed consent form (ICF) 9. Willing to follow the protocol requirements and comply with protocol restrictions Parts B and C – subjects with MCI or PD MCI or PD subjects must meet the following criteria: 10. Males and females aged 40-75 years (inclusive) at the time of informed consent 11. Montreal Cognitive Assessment (MoCA) score =18 and =26 12. 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. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a condom during each episode of penile-vaginal penetration until after the End of Study Visit. 13. 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: a. use a reliable method of birth control, or b. monogamous relationship with a male partner of confirmed sterility, or c. practice complete abstinence 14. Females of non-childbearing potential may be enrolled if it is documented that they are postmenopausal or have undergone surgical sterilization 15. Stable medical conditions for 3 months prior to Screening visit (e.g., diabetes, hypertension, dyslipidemia) 16. If already being administered, vitamin E (up to 400 IU daily), estrogens, aspirin (75-300 mg daily), blood pressure medications (except for adrenergic agents), diabetic medications, and cholesterol-lowering agents for 3 months prior to screening is allowed. 17. In generally good health, in
Exclusion criteria
Exclusion criteria: A subject with any of the following criteria will not be eligible for participation. 1. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, metabolic, psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator. 2. History of malignant disease, including solid tumours and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured). 3. A calculated creatinine clearance of =70 mL/min according to the Cockcroft-Gault equation. 4. Uncontrolled hypertension (systolic blood pressure = 140 or diastolic blood pressure = 90 mmHg) at Screening or Day -1. 5. History of drug or alcohol abuse =12 months prior to Screening. 6. A positive test for drugs of abuse or alcohol during Screening. 7. Unwilling or unable to abstain from alcohol from 2 days prior to Day 1 until end-of-study assessments. 8. Use of over-the-counter medication (other than paracetamol up to 2 g per day), or herbal supplements/products during Screening or throughout study, unless approved by both the Principal Investigator and the CuraSen Medical Monitor. 9. Subjects on monoamine oxidase type B inhibitors, dopamine agonists or catechol-O-methyltransferase inhibitors are not allowed. 10. Current or prior treatment with any beta agonists or beta blockers within the last month prior to Day 1. 11. Opioid use within 1 month prior to screening or during the study. 12. Use of St. John’s Wort or Ginkgo Biloba within 1 month prior to study enrollment. 13. 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). Subjects with immunity to hepatitis B (defined as negative HBsAg and positive hepatitis B surface antibody [HBsAb]) are eligible to participate in the study. 14. Positive screening test for human immunodeficiency virus (HIV). 15. Positive screening test for or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or documented history of prior infection. 16. Clinically significant abnormal clinical laboratory test values, as determined by the Investigator, or any value of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that is above 1.5 X above the upper limit of normal, or any out-of-range value for serum sodium or potassium. Screening tests may be repeated once at the discretion of the Investigator. 17. Clinically significant laboratory or ECG abnormality that could be a safety issue in the study, including QT using Fredericia’s correction of QT interval (QTcF) >450 msec (males) or >470 msec (females). 18. History of angina, heart failure, coronary insufficiency, cardiac arrythmias, hyperthyroidism, hypothyroidism, or convulsion disorders. 19. 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 enrolment in any other study treatment or disease study. 20. Donation or loss of =500 mL of blood or plasma within 30 days prior to dosing. 21. Inability to undergo a clinical MRI of the brain due to claustrophobia, or other contraindications to undergoing an MRI of the brain including, but not limited to, pacemakers; implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clip
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are: Part A To evaluate the effects of CST-139 on cerebral perfusion in healthy subjects. Part B To evaluate the effects of multiple doses of CST-139 on cerebral perfusion in subjects with Mild Cognitive Impairment (MCI) or Parkinson’s Disease (PD). Part C To evaluate the effects of multiple doses of CST-103 on cerebral perfusion in subjects with MCI or PD.;Secondary Objective: The secondary objectives include the following: Part A 1. To examine the effects of CST-139 on cognition in healthy subjects 2. To assess the safety and tolerability of CST-139 3. To characterize the pharmacokinetic (PK) profile of CST-139 Part B 1. To examine the effects of multiple doses of CST-139 on cognition in subjects with MCI or PD 2. To assess the safety and tolerability of CST-139 3. To characterize the PK profile of CST-139 Part C 1. To examine the effects of multiple doses of CST-103 on cognition in subjects with MCI or PD 2. To assess the safety and tolerability of CST-103 3. To characterize the PK profile of CST-103;Primary end point(s): The primary endpoints are: Part A The change in cerebral perfusion after oral administration of CST-139 as measured by Arterial Spin Labeling (ASL) MRI in healthy subjects. Part B The change in cerebral perfusion after oral administration of multiple doses of CST-139 as measured by ASL MRI in subjects with MCI or PD. Part C The change in cerebral perfusion after oral administration of multiple doses of CST-103 as measured by ASL MRI in subjects with MCI or PD.;Timepoint(s) of evaluation of this end point: Please refer to the protocol for details. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: 1. CANTAB cognitive assessments, which include the following: • Reaction Time (RTI) • Verbal Recognition Memory (VRM) Phase I • Adaptive Tracking Task (ATT) • Paired Associates Learning Task (PAL) • Delayed Verbal Recall 2. Adverse events, ECGs, vitals, laboratory safety tests 3. Plasma PK parameters of CST-103 and CST-139 (including Cmax, tmax, AUCt, AUCinf , t1/2);Timepoint(s) of evaluation of this end point: Please refer to the protocol for details. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Information Desk
CuraSen Therapeutics, Inc.
Outcome results
None listed