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

NCT04291859 | Completed Phase 1 FDA Drug

• 2 other identifiers: 18252A2019-001280-77
• Study Type: interventional
• Target: 57
• Locations: 5 countries
• Sites: 15

Brief Summary

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (3)

• 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 5.5 Months

• Cmax of Lu AF28996

  Maximum observed plasma concentration of Lu AF28996

  0 (predose) to 24 hours postdose on Day 1 to Day 47

• Tmax of Lu AF28996

  Nominal Time Corresponding to the Occurrence of Cmax

  0 (predose) to 24 hours postdose on Day 1 to Day 47

Study Arms (1)

Lu AF28996

EXPERIMENTAL

Participants in Part A will receive ascending oral doses of Lu AF28996 OD for 14 days in all OD cohorts, followed by down-titration as per Investigator's judgement. For the BID Cohort A1, participants will receive Lu AF28996 BID for 24 days, followed by down-titration as per Investigator's judgement. For the BID Cohort A2, participants will receive Lu AF28996 BID for 39 days, followed by down-titration as per Investigator's judgement. Participants in Part B (Cohorts B1, B2, and B3) will receive Lu AF28996 BID for 41 days, followed by down-titration as per Investigator's judgement

Drug: Lu AF28996

Interventions

Lu AF28996 DRUG

capsule, orally, doses and dose escalation scheme will be decided upon at dosing conferences

Lu AF28996

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants diagnosed with idiopathic PD (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), with not more than 1 first-degree relative who has PD.
• Participants must have a Modified Hoehn and Yahr score ≤4 in the OFF state and ≤3 in the ON state, and a Mini Mental State Examination score \>25.
• The OFF/ON amplitude on the MDS-UPDRS Part III at screening must be minimum 30% difference.
• 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, as evaluated by the investigator. This will be documented using a participant ON/OFF state registration over 3 consecutive days prior to enrolment.
• Allowed concomitant medication for PD during the study includes levodopa, monoamine oxidase B inhibitors, COMT inhibitors, anticholinergics, and amantadine. Dopamine agonists are not allowed and should be discontinued ≥4 weeks prior to dosing with Lu AF28996 and until the end of the study.
• Participants diagnosed with idiopathic PD (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), with not more than 1 first-degree relative who has PD.
• Participants must have a Modified Hoehn and Yahr score ≥2 to ≤4 in the OFF state and ≤3 in the ON state, a MDS-UPDRS Part IV, 4.5 score of 1 or 2, and a MDS-UPDRS Part IV, 4.2 score ≥2 (at least mild functional impact), and a Mini Mental State Examination score \>25 at the Screening Visit.
• Participants must currently have a good response to levodopa and be 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 and LEDD between 400 and 1600, inclusive) for at least 4 weeks prior to screening.
• Participants must experience recognizable and predictable motor fluctuations (with ≥3 hours of OFF periods in the awake time, including predictable morning OFF episodes), causing clinically significant disability during 3 months prior to enrolment, as evaluated by the investigator. The criteria will be documented using Hauser Diary over 3 consecutive days prior to enrolment.
• Participants must experience ≥1 hour daily ON time with troublesome dyskinesia (TD) in the awake time (TD/24 hours while awake) during the last 3 months prior to enrolment as evaluated by the investigator. The criteria will be documented using the Hauser Diary over 3 consecutive days prior to enrolment.
• Allowed concomitant medication for PD during the study includes levodopa, dopamine agonists, if allowed daily dose, monoamine oxidase B inhibitors, COMT inhibitors, anticholinergics, and amantadine.

You may not qualify if:

• 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.
• Participant has been treated with apomorphine (pen/pump), and/or inhaled levodopa and/or levodopa/carbidopa intestinal gel (LCIG),and/or subcutaneous foslevodopa/foscarbidopa within 6 weeks prior to the Baseline Visit.
• Participants formerly treated with oral or transdermal dopamine agonists must have discontinued 4 weeks prior to screening.
• Participant has a history of Dopamine Agonist Withdrawal Syndrome (DAWS) when dopamine agonists were previously discontinued or reduced.

Sponsors & Collaborators

• H. Lundbeck A/S: lead

Study Sites (15)

CenExel Los Alamitos

Los Alamitos, California, 90720, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Velocity

Hallandale, Florida, 33009, United States

Location

Parkinson's Disease Treatment Center of SW FL

Port Charlotte, Florida, 33980, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Neurology Consultants of Nebraska

Omaha, Nebraska, 68154, United States

Location

Inland Nortwest Research

Spokane, Washington, 99202, United States

Location

Caen Normandy University

Caen, Basse-Normandie, 14033, France

Location

Curiositas-ad-sanum

Hamburg, 83527, Germany

Location

QPS Netherlands BV

Leeuwarden, 8934 AD, Netherlands

Location

Hospital Vall d´Hebron

Barcelona, 08035, Spain

Location

Hosp. General Catalunya

Mira-Sol, 08195, Spain

Location

Virgen Del Roccio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Email contact via H. Lundbeck A/S

  LundbeckClinicalTrials@Lundbeck.com

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 2, 2020
• Study Start: February 26, 2020
• Primary Completion: October 14, 2025
• Study Completion: February 12, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

ES (3); DE (1); US (9); NL (1); FR (1)