Flexible-Dose Trial in Early Parkinson's Disease (PD) (TEMPO-2)

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinsonian Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases Read More

Key Inclusion Criteria:

• Male and female participants aged 40 to 80 years, inclusive, at the time of signing the informed consent form (ICF).
• Sexually active men or women of childbearing potential must agree to use acceptable (at minimum) or highly effective birth control, or remain abstinent during the trial and for 4 weeks after the last dose of trial treatment.
• Participants who are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria.
• Participants with modified Hoehn and Yahr stage 1, 1.5, or 2.
• Participants with disease duration (from time of diagnosis) of less than (<) 3 years and disease progression in the 3 years before signing the ICF.
• Participants with an MDS-UPDRS Part II score >=2 and Part III score >=10 at the Screening Visit and at the Baseline Visit.
• Participants with early PD who, in the opinion of the investigator, require pharmacologic intervention for disease management.
• Participants who are treatment naive or have a history of prior incidental treatment with dopaminergic agents (including L-Dopa and dopamine receptor agonist medications) for <3 months in total but not within 2 months of the Baseline Visit. Prior and concurrent use of MAO-B inhibitors is permitted if use was initiated >90 days before the Baseline Visit and the dosage will remain stable for the duration of the trial (ie, no change in the MAO-B inhibitor dose is permitted during the trial).
• Participants who are willing and able to refrain from any PD medications that are not permitted by the protocol (including dopaminergic agents) throughout participation in the trial.

Key Exclusion Criteria:

• Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supra nuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or post stroke parkinsonism).
• Participants with a history of nonresponse or insufficient response to L-Dopa at therapeutic dosages.
• Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5).
• Participants with the presence of or history of brain tumor, hospitalization for severe head trauma, epilepsy (as defined by the International League Against Epilepsy), or seizures.
• Participants with a history of psychosis or hallucinations within the previous 12 months.
• Participants who answer "yes" on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR Participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide.
• Participants with substance abuse or dependence disorder, including alcohol, benzodiazepines, and opioids, but excluding nicotine, within the past 6 months (180 days).
• Participants with dementia or cognitive impairment that, in the judgement of the investigator, would exclude the participant from understanding the ICF or participating in the trial.
• Participants with any condition that could possibly affect drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding).
• Participants who have a positive result for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies at screening.
• Participants with a history of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical intervention; second- or third-degree atrioventricular block; sick sinus syndrome; severe or unstable angina; or congestive heart failure within the last 12 months. A recent (less than or equal to [<=] 12 months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
• Participants with a history of neuroleptic malignant syndrome.
• Participants who are currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration).
• Participants with a positive urine drug screen for illicit drugs are excluded and may not be retested or rescreened. Participants with a positive urine drug screen resulting from use of marijuana (any Tetrahydrocannabinol [THC]-containing product), prescription, or over-the-counter medications or products that, in the investigator's documented opinion, do not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results may continue evaluation for the trial following consultation and approval by the medical monitor.
• Participants with a Montreal Cognitive Assessment (MoCA) score <26.
• Participants with clinically significant orthostatic hypotension (eg, syncope).
• Participants with a 12-lead ECG demonstrating a QTcF interval >450 msec.
• Participants with moderate or severe renal impairment (creatinine clearance as estimated by Cockcroft-Gault formula <30 mL/min or on dialysis).

• Participants with any of the following abnormalities in clinical laboratory tests at the Screening Visit, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary:

  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >=3 × Upper Limit Normal (ULN).
  • Total bilirubin >=1.5 × ULN. Participants with a history of Gilbert's syndrome may be eligible provided they have a value <ULN for direct bilirubin.
• Participants with other abnormal laboratory test results, vital sign results, or ECG findings unless, in the judgment of the investigator, the findings are not medically significant and would not impact the safety of the participants or the interpretation of the trial results.