An Exploratory Study Investigating Safety, Tolerability and Pharmacokinetics of Ascending Doses of Lu AE04621 in Parkinson Disease Patients

Interventional, Open-label, Exploratory Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Lu AE04621 and the Active Metabolite Lu AA40326 After Ascending Oral Doses of Lu AE04621 to Patients With Parkinson's Disease

To evaluate the safety, tolerability, pharmacokinetics, and efficacy of the Lu AE04621 and metabolite after ascending oral doses of Lu AE04621 in patients with Parkinson's Disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: 0.04 mg Lu AE04621; Drug: 0.08 mg Lu AE04621; Drug: 0.2 mg Lu AE04621; Drug: 0.4 mg Lu AE04621; Drug: 0.6 mg Lu AE04621; Drug: 0.8 mg Lu AE04621; Drug: 1.0 mg Lu AE04621; Drug: 1.2 mg Lu AE04621

Detailed Description

The study comprised 5 cohorts (Cohorts 1 to 5), with each cohort consisting of 3 patients with Parkinson's disease (men and/or women). Each patient will be treated for 3 or 4 days, with increasing dose each day.

Dosing regimen will be decided at a dosing conferences. Dose levels can be increased, maintained or reduced both between cohorts but also within same cohort. The results are presented by dose level and reflect the actual doses administered.

A follow-up safety visit was scheduled approximately 7 days after the last dose of IMP.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hallandale Beach, Florida, United States
      • US1251
    • Orlando, Florida, United States
      • US1126
  • Illinois
    • Chicago, Illinois, United States
      • US1352
  • Michigan
    • Detroit, Michigan, United States
      • US1084

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient is diagnosed with idiopathic Parkinson Disease (consistent with the UK Parkinson's Disease Society Brain Bank Criteria for the Diagnosis of PD).
• The patient's Hoehn and Yahr Staging score is ≤ 3 in the "ON" state.
• The patient experiences motor fluctuations with at least 2.5 hours of "OFF" periods in the awake time and has predictable morning "OFF" episodes, which have been consistent within the past 4 weeks.
• The patient currently has a good response to L-DOPA and has been receiving a stable dose of L-DOPA (≥3 doses per day of standard L-DOPA or ≥3 doses per day of Carbidopa and L-DOPA, Extended-Release Capsules) during at least four weeks prior to screening.

Exclusion Criteria:

• The patient has cognitive impairment, defined as a Mini Mental State Examination(MMSE) score ≤ 26 at the Screening Visit.
• The patient has severe disabling dyskinesia
• The patient takes or has taken disallowed recent or concomitant medication (CYP2D6 inhibitors, CYP 3A4 substrate, Dopamine agonists, 5 HT3 antagonists, Anti-viral (Amantadine))

Other protocol defined inclusion and exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.04 mg Lu AE04621; Patients having received a dose of 0.04 mg, independent of which Cohort they belong to.	Drug: 0.04 mg Lu AE04621; 0.04 mg dose group
Experimental: 0.08 mg Lu AE04621; Patients having received a dose of 0.08 mg, independent of which Cohort they belong to.	Drug: 0.08 mg Lu AE04621; 0.08mg dose group
Experimental: 0.2 mg Lu AE04621; Patients having received a dose of 0.2 mg, independent of which Cohort they belong to.	Drug: 0.2 mg Lu AE04621; 0.2 mg dose group
Experimental: 0.4 mg Lu AE04621; Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.	Drug: 0.4 mg Lu AE04621; 0.4 mg dose group
Experimental: 0.6 mg Lu AE04621; Patients having received a dose of 0.6 mg, independent of which Cohort they belong to.	Drug: 0.6 mg Lu AE04621; 0.6 mg dose group
Experimental: 0.8 mg Lu AE04621; Patients having received a dose of 0.8 mg, independent of which Cohort they belong to.	Drug: 0.8 mg Lu AE04621; 0.8 mg dose group
Experimental: 1.0 mg Lu AE04621; Patients having received a dose of 1.0 mg, independent of which Cohort they belong to.	Drug: 1.0 mg Lu AE04621; 1.0 mg dose group
Experimental: 1.2 mg Lu AE04621; Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.	Drug: 1.2 mg Lu AE04621; 1.2 mg dose group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG)	Number of patients with an adverse event	Baseline to day 11
Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621		From dosing to up to 24 hours after dosing
Maximum Observed Concentration (Cmax) for Lu AE04621		From dosing to up to 24 hours after dosing
Apparent Elimination Half-life of Lu AE04621 in Plasma (t½)		From dosing to up to 24 hours after dosing
Time to Onset of "ON" Time After Lu AE04621 Administration	"ON" state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to "ON" and "OFF" state. "OFF" state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'.	From dosing to 90 minutes after dosing
Duration of "ON" Time	"ON" state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to "ON" and "OFF" state. "OFF" state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Outcome measured in minutes. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON' following administration of Lu AE04621.	From dosing up to 24h post-dose

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 6, 2016
• First Posted (Estimate): January 7, 2016

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 16779A