A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered BT-409 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of BT-409 in Adults with Parkinson’s disease.

Exclusion Criteria30

• A potential participant who meets any of the following criteria will be excluded from participation in this study:
• Evidence of any active or chronic disease or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram [ECG]). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance.
• Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy participants.
• A medical history of clinically significant and debilitating dyskinesia or ON-OFF phenomenons.
• MMSE score less than 24 during screening.
• Serological evidence of active, inadequately treated hepatitis B infection (defined as positive Hepatitis B surface antigen (HBsAg)), or hepatitis C infection (defined as a positive Hepatitis C antibody (HCV Ab) and detectable HCV RNA), or positive human immunodeficiency virus antibody (HIV Ab) at screening.
• Have ALT or AST levels greater than or equal to 2 times upper limit of normal (ULN) or a bilirubin level greater than or equal to 1.5 times ULN unless due to Gilbert’s syndrome.
• History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell carcinomas and squamous cell carcinomas of the skin that have been completely excised and considered cured greater than 1 year prior to Baseline). Participants with cancers in remission for greater than 5 years prior to Baseline may be included.
• Participants with uncontrolled hypertension. Participants with a history of stable hypertension treated with allowed antihypertensive agents may be included.
• Unstable psychiatric illness, including psychosis, suicidal ideation, or untreated major depression, within 90 days before Screening.
• Are actively suicidal (e.g., any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the C-SSRS (score of “YES” on suicidal ideation item 4 or 5 within 6 months prior to Screening Visit) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator.
• Systolic blood pressure (SBP) greater than 160 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 95 or less than 50 mm Hg at screening.
• Have a thyroid stimulating hormone (TSH) level of 1.2 x ULN on or off stable treatment for hyperthyroidism or hypothyroidism. If TSH is abnormal, evaluate reflex Free T3 and Free T4. If reflex testing is normal, the assessment of normal thyroid function will be determined based on the judgement of the Investigator.
• Abnormal findings in the resting ECG at screening defined as:
• a. QTcF greater than 450 or lesser than 300 msec for men and QTcF greater than 470 or lesser than 300 msec for women
• b. Symptomatic resting bradycardia (HR lesser than 45 bpm) or tachycardia (HR greater than 100 bpm)
• c. Personal or family history of congenital long QT syndrome or sudden death;
• d. ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves);
• e. Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker.
• Participation in an investigational drug or device study, more than four times per year, and last dosing of previous study was within 90, or 5 half-lives (whichever is longest) prior to first dosing of this study. For monoclonal clonal antibodies against alpha-synuclein and tau, the interval should be at least 6 months.
• History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent.
• Positive test for drugs of abuse at screening or pre-dose.
• Alcohol will not be allowed from at least 24 hours before screening or before Day -1 until EoS.
• Smoker of more than 5 cigarettes per day prior to screening or who use tobacco products equivalent to more than 5 cigarettes per day and unable to abstain from smoking whilst in the unit.
• Is demonstrating excess in caffeine consumption (more than eight cups of coffee or equivalent per day.
• Any confirmed significant allergic reactions (difficulty breathing or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).
• Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during this study.
• Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
• Previous possible exposure to the study compound.
• Any condition or findings, such as signs of increased intracranial pressure, skin infection at puncture site, spinal infection, severe bleeding/clotting disorders, brain mass, recent neurosurgery, spinal disease, where a lumbar puncture is contraindicated or that may make Cerebrospinal Fluid (CSF) collection difficult.