Lu AF28996 in Participants With Parkinson's Disease (PD)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety of Lu AF28996, how well it is tolerated and what the body does to the drug in participants with Parkinson's disease.

Detailed Description
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The study will consist of once daily (OD) cohorts (OD Cohort 1 to 4[5]) as well as twice daily (BID) cohorts (BID Cohorts A1 and A2). The study has been re-designed following the inclusion of 2 participants. The study will consist of 4 cohorts (men or women). OD Cohort 1 and OD Cohort 2 are complete and included 2 participants in OD Cohort 1 and 3 participants in OD Cohort 2. New participants will start with Cohort 3. OD Cohorts 3 and 4 will each consist of 4 participants with the possibility of adding 1 more cohort including 4 participants (OD Cohort 5). In BID Cohort A1, 8 participants are planned for enrolment, and in BID Cohort A2, 12 participants are planned for enrolment.

Official Title
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Interventional, Open-label, Exploratory Study, Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Lu AF28996 in Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Lu AF28996


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women diagnosed with idiopathic PD (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), Modified Hoehn and Yahr Score ≤4 in the 'OFF' state and ≤3 in 'ON' state and a Mini Mental State Examination Score >25. Participants must currently have a good response to levodopa, and have been receiving a stable dose of levodopa (≥3 doses per day of levodopa/dopa decarboxylase inhibitor therapy or ≥3 doses per day of levodopa Extended-Release Capsules) ≥4 weeks prior to screening. Participants must experience recognizable and predictable motor fluctuations (with at least 1.5 hours of OFF-periods in the awake time, including predictable morning OFF episodes) causing clinically significant disability during the 7-week screening period. This will be documented using a participant ON/OFF state registration over 3 consecutive days prior to enrolment. Exclusion Criteria: The participant has or had one or more of the following conditions that are considered clinically relevant in the context of the study; other neurological disorder, psychiatric disorder, seizure disorder or encephalopathy, respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrinological disorder, haematological disorder, infectious disorder, any clinically significant immunological condition, or a history of narrow-angle glaucoma. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lu AF28996<br>Participants will receive ascending oral doses of Lu AF28996 OD for 14 days (Day 1 to Day 14) in all OD Cohorts 1-4 (5). On Day 15, the participant will initiate down-titration of Lu AF28996 as per Investigator's judgement. For the BID Cohort A1, participants will receive Lu AF28996 BID for 24 days (Day 1 to Day 24), followed by down-titration as per Investigator's judgement. For the BID Cohort A2, participants will receive Lu AF28996 BID for 39 days (Day 1 to Day 39), followed by down-titration as per Investigator's judgement. | Drug: Lu AF28996<br>* capsule, orally, doses and dose escalation scheme will be decided upon at dosing conferences<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events | Safety and tolerability based on the safety assessments (clinical safety laboratory tests, vital signs, weight, ECG parameters and physical examination) | From Baseline to Day 62 | 
| AUC(last) of Lu AF28996 | Area under the plasma concentration time curve from zero to last quantifiable plasma concentration | 0 (predose) to 24 hours postdose on Day 1 to Day 39 | 
| AUC(0-24h) of Lu AF28996 | Area under the plasma concentration time curve from zero to 24 hours post dose | 0 (predose) to 24 hours postdose on Day 1 to Day 39 | 
| Cmax of Lu AF28996 | Maximum observed plasma concentration of Lu AF28996 | 0 (predose) to 24 hours postdose on Day 1 to Day 39 | 
| CL/F of Lu AF28996 | Oral clearance for Lu AF28996 in plasma | 0 (predose) to 24 hours postdose on Day 1 to Day 39 | 
| Amount of Lu AF28996, Lu AF28995, Lu AF29308, and Lu AF29309 Excreted in Urine |  | 0 (predose) to 24 hours postdose on Day 1 to Day 62 |