TEMPO-1
Brief summary
The purpose of this study is to evaluate the clinical efficacy, safety and pharmacokinetics (PK) of 2 fixed doses of tavapadon and placebo in participants with early PD.
Interventional study
- 1
- 2
- 3
- 4
Age:
From 40 Years to 80 Years.
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 naïve or have a history of prior incidental treatment
with dopaminergic agents (including Levodopa [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 monoamine oxidase B (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 (i.e, 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 Columbia-Suicide Severity Rating Scale (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.