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

NCT02649608 | Completed Phase 1 Results DMC

• 1 other identifier: 16779A
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (8)

0.04 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 0.04 mg, independent of which Cohort they belong to.

Drug: 0.04 mg Lu AE04621

0.08 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 0.08 mg, independent of which Cohort they belong to.

Drug: 0.08 mg Lu AE04621

0.2 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 0.2 mg, independent of which Cohort they belong to.

Drug: 0.2 mg Lu AE04621

0.4 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.

Drug: 0.4 mg Lu AE04621

0.6 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 0.6 mg, independent of which Cohort they belong to.

Drug: 0.6 mg Lu AE04621

0.8 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 0.8 mg, independent of which Cohort they belong to.

Drug: 0.8 mg Lu AE04621

1.0 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 1.0 mg, independent of which Cohort they belong to.

Drug: 1.0 mg Lu AE04621

1.2 mg Lu AE04621

EXPERIMENTAL

Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.

Drug: 1.2 mg Lu AE04621

Interventions

0.04 mg Lu AE04621 DRUG

0.04 mg dose group

0.04 mg Lu AE04621

0.08 mg Lu AE04621 DRUG

0.08mg dose group

0.08 mg Lu AE04621

0.2 mg Lu AE04621 DRUG

0.2 mg dose group

0.2 mg Lu AE04621

0.4 mg Lu AE04621 DRUG

0.4 mg dose group

0.4 mg Lu AE04621

0.6 mg Lu AE04621 DRUG

0.6 mg dose group

0.6 mg Lu AE04621

0.8 mg Lu AE04621 DRUG

0.8 mg dose group

0.8 mg Lu AE04621

1.0 mg Lu AE04621 DRUG

1.0 mg dose group

1.0 mg Lu AE04621

1.2 mg Lu AE04621 DRUG

1.2 mg dose group

1.2 mg Lu AE04621

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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))

Sponsors & Collaborators

• H. Lundbeck A/S: lead

Study Sites (4)

US1251

Hallandale, Florida, United States

Location

US1126

Orlando, Florida, United States

Location

US1352

Chicago, Illinois, United States

Location

US1084

Detroit, Michigan, United States

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

Limitations and Caveats

Because of the limit of quantification, some missing and/or unreliable data prevented the calculation of some of the PK parameters (AUC0-24hours, apparent elimination half-life) for some of the dose groups.

Results Point of Contact

• Title: Email contact via H. Lundbeck A/S
• Organization: H. Lundbeck A/S

LundbeckClinicalTrials@Lundbeck.com

+45 36301311

Study Officials

• Email contact via H. Lundbeck A/S

  LundbeckClinicalTrials@Lundbeck.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 7, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 24, 2021
• Results First Posted: December 2, 2019

Record last verified: 2019-11

Locations

US (4)