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

Phase 1

Completed

Conditions: Parkinson Disease

Interventions: Drug: 0.2 mg Lu AE04621
Drug: 1.0 mg Lu AE04621
Drug: 0.04 mg Lu AE04621
Drug: 0.6 mg Lu AE04621
Drug: 1.2 mg Lu AE04621
Drug: 0.8 mg Lu AE04621
Drug: 0.4 mg Lu AE04621
Drug: 0.08 mg Lu AE04621

Registration Number: NCT02649608

Lead Sponsor: H. Lundbeck A/S

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
0.2 mg Lu AE04621	0.2 mg Lu AE04621	Patients having received a dose of 0.2 mg, independent of which Cohort they belong to.
1.0 mg Lu AE04621	1.0 mg Lu AE04621	Patients having received a dose of 1.0 mg, independent of which Cohort they belong to.
0.04 mg Lu AE04621	0.04 mg Lu AE04621	Patients having received a dose of 0.04 mg, independent of which Cohort they belong to.
0.6 mg Lu AE04621	0.6 mg Lu AE04621	Patients having received a dose of 0.6 mg, independent of which Cohort they belong to.
1.2 mg Lu AE04621	1.2 mg Lu AE04621	Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.
0.8 mg Lu AE04621	0.8 mg Lu AE04621	Patients having received a dose of 0.8 mg, independent of which Cohort they belong to.
0.4 mg Lu AE04621	0.4 mg Lu AE04621	Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.
0.08 mg Lu AE04621	0.08 mg Lu AE04621	Patients having received a dose of 0.08 mg, independent of which Cohort they belong to.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Concentration (Cmax) for Lu AE04621	From dosing to up to 24 hours after dosing
Time to Onset of "ON" Time After Lu AE04621 Administration	From dosing to 90 minutes after dosing	"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'.
Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG)	Baseline to day 11	Number of patients with an adverse event
Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) 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
Duration of "ON" Time	From dosing up to 24h post-dose	"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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (4): US1251
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Hallandale Beach, Florida, United States
US1126
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Orlando, Florida, United States
US1352
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Chicago, Illinois, United States
US1084
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Detroit, Michigan, United States