Fixed-Dose Trial in Early Parkinson's Disease (PD)

Phase 3

Completed

Conditions: Parkinson Disease

Interventions: Drug: Tavapadon
Drug: Placebo

Registration Number: NCT04201093

Lead Sponsor: AbbVie

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 529

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tavapadon 5 mg	Tavapadon	Participants will receive tavapadon tablet titrated up to 5 milligram (mg) once daily (QD) orally for 27 weeks.
Tavapadon 15 mg	Tavapadon	Participants will receive tavapadon tablet titrated up to 15 milligram (mg) QD orally for 27 weeks.
Placebo	Placebo	Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the MDS-UPDRS Parts II and III Combined Score	Week 26	The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the MDS-UPDRS Part II Score	Week 26	The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function.
Percentage of Responders With a Score of "Much Improved" or "Very Much Improved" on PGIC	Week 26	The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Change From Baseline in the MDS-UPDRS Parts II and III Combined Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184.
Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 1, 2, and 3 combined is the sum of Part 1, Part 2, and Part 3 scores at each assessment time for each participant. The combined score assesses 44 items with score range: 0-236.
Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function.
Change From Baseline in the CGI-S Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Global Impression - Severity of Illness (CGI-S) Score is a clinician's impression of a participant's severity of illness on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (normal) to 7 (among the most extremely ill participants). Higher values represent a worse outcome.
Change From Baseline in the CGI-I Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Clinical Global Impression - Improvement (CGI-I) Score is a clinician's impression of how much the participant's illness has improved or worsened relative to the baseline on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Change From Baseline in the Epworth Sleepiness Scale (ESS)	Week 26	The ESS is an 8-question, participant questionnaire that is intended to measure daytime sleepiness. It assesses the likelihood of dozing off or falling asleep in the following common situations: sitting and reading, sitting inactive in a public place as a passenger in a car for an hour or more without stopping for a break, lying down to rest when circumstances permit, sitting and talking to someone, sitting quietly after a meal without alcohol, and in a car while stopped for a few minutes in traffic or at a light. Each situation is rated on a 4-point (0-3) scale with scores ranging from 0 (would never nod off) to 3 (high chance of nodding off). Higher values represent a worse outcome.
Change From Baseline in the PGIC Score	Week 5, 8, 11, 14, 18, 22, 26, and 27	The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Change From Baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)	Week 26	QUIP-RS is a questionnaire for impulse-compulsive disorders in Parkinson's disease rating scale to assess impulse control disorders (ICD). The QUIP-RS has 4 primary questions that pertain to commonly reported thoughts, urges/desires, and behaviors associated with ICDs, each of which is applied to 4 ICDs (compulsive gambling, buying, eating, sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). The QUIP-RS uses a 5-point Likert scale (score 0-4 \[0 means "never" and 4 means "very often"\] for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16, with a higher score indicating greater severity (frequency) of symptoms. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112. A higher score indicating greater severity of symptoms.
Columbia-Suicide Severity Rating Scale (C-SSRS)	Week 27	The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation (SI) categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose of study drug until 190 days following last dose of study drug.	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Trial Locations

Locations (72): Birmingham, Alabama
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Birmingham, Alabama, United States
Little Rock, Arkansas
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Little Rock, Arkansas, United States
Fountain Valley, California
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Fountain Valley, California, United States
Los Angeles, California
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Los Angeles, California, United States
Pasadena, California
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Pasadena, California, United States
Englewood, Colorado
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Englewood, Colorado, United States
Adventura, Florida
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Adventura, Florida, United States
Boca Raton, Florida
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Boca Raton, Florida, United States
Tampa, Florida
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Tampa, Florida, United States
Augusta, Georgia
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Augusta, Georgia, United States
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Birmingham, Alabama
🇺🇸Birmingham, Alabama, United States