Clinical trial NCT02649608: An Exploratory Study Investigating Safety, Tolerability and Pharmacokinetics of Ascending Doses of Lu AE04621 in Parkinson Disease Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2016-01-07
Enrollment: 15
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The study comprised 5 cohorts (Cohorts 1 to 5), with each cohort consisting of 3 patients (men and/or women). The dosing regimen planned for Cohort 1 was a dose of 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, and a dose of 0.6 mg Lu AE04621 on Day 3. • The dosing regimen planned for Cohort 2 was 0.4 mg Lu AE04621 on Day 1 followed by a dose of 0.6 mg Lu AE04621 on Day 2, and a dose of 0.8 mg Lu AE04621 on Day 3. The dosing regimen planned for Cohort 3 was 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, a dose of 0.6 mg Lu AE04621 on Day 3, and a dose of 1.0 mg Lu AE04621 on Day 4. The dosing regimen planned for Cohorts 4 and 5 was 0.2 mg Lu AE04621 on Day 1 followed by a dose of 0.4 mg Lu AE04621 on Day 2, a dose of 0.6 mg Lu AE04621 on Day 3, and a dose of 1.2 mg Lu AE04621 on Day 4. The results are presented by dose groups and are based on the actual doses administered.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG)
timeFrame: Baseline to day 11
measure: Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621
timeFrame: From dosing to up to 24 hours after dosing
measure: Maximum Observed Concentration (Cmax) for Lu AE04621
timeFrame: From dosing to up to 24 hours after dosing
measure: Apparent Elimination Half-life of Lu AE04621 in Plasma (t½)
timeFrame: From dosing to up to 24 hours after dosing
measure: Time to Onset of "ON" Time After Lu AE04621 Administration
timeFrame: From dosing to 90 minutes after dosing
measure: Duration of "ON" Time
timeFrame: From dosing up to 24h post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: US1251
state: Florida
city: Orlando
country: United States
facility: US1126
state: Florida
city: Chicago
country: United States
facility: US1352
state: Illinois
city: Detroit
country: United States
facility: US1084
state: Michigan
Study officials:
affiliation: LundbeckClinicalTrials@Lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: