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

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02649608
• Other study ID #: 16779A
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: December 2016

Study information

• Verified date: November 2019
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• 0.04 mg Lu AE04621
0.04 mg dose group
• 0.08 mg Lu AE04621
0.08mg dose group
• 0.2 mg Lu AE04621
0.2 mg dose group
• 0.4 mg Lu AE04621
0.4 mg dose group
• 0.6 mg Lu AE04621
0.6 mg dose group
• 0.8 mg Lu AE04621
0.8 mg dose group
• 1.0 mg Lu AE04621
1.0 mg dose group
• 1.2 mg Lu AE04621
1.2 mg dose group

Locations

Country	Name	City	State
United States	US1352	Chicago	Illinois
United States	US1084	Detroit	Michigan
United States	US1251	Hallandale Beach	Florida
United States	US1126	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621		From dosing to up to 24 hours after dosing
Primary	Maximum Observed Concentration (Cmax) for Lu AE04621		From dosing to up to 24 hours after dosing
Primary	Apparent Elimination Half-life of Lu AE04621 in Plasma (t½)		From dosing to up to 24 hours after dosing
Primary	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
Primary	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