A Study to Examine APL-130277 in Patients With Parkinson's Disease

NCT02228590 | Completed Phase 2 Results

• 1 other identifier: CTH-105
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is to evaluate the efficacy, tolerability and safety of single treatments of APL-130277 in 16 patients with Parkinson's Disease (PD)

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease

Outcome Measures

Primary Outcomes (9)

• The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277

  Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).

  At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

• Time to 'ON' State From Time of Dosing of APL-130277

  Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.

  At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

• Duration of 'ON' Response From Time of Dosing of APL-130277

  Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.

  At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

• Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode

  Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.

  At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

• Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)

  The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).

  Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.

• PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)

  The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.

  Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.

• PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)

  The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.

  Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.

• PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)

  The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.

  Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.

• PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)

  The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).

  Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.

Secondary Outcomes (1)

• Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment

  At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

Study Arms (1)

APL-130277

OTHER

open label baseline comparison

Drug: APL-130277

Interventions

APL-130277 DRUG

Apomorphine Hydrochloride, Sublingual Thin Film

Also known as: Apomorphine Hydrochloride, Sublingual Thin Film

APL-130277

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age.
• Clinical diagnosis of Idiopathic PD
• Receiving stable doses of L-dopa +/- other adjunctive PD therapy for at least 4 weeks before study participation.
• At least one OFF episode per day and a total daily OFF time of \> 2 hours duration.
• Experience predictable OFF episodes in the morning on awakening prior to receiving morning dose of levodopa.
• Stage I to III on the Hoehn and Yahr scale in the "ON" state.
• If female and of childbearing potential, must agree to use one of the following methods of birth control:
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
• Able to understand the consent form, and to provide written informed consent.

You may not qualify if:

• Atypical or secondary parkinsonism
• Changes in L-dopa or other PD drug dosing regimens 4 weeks before the screening visit.
• Past treatment with any form of apomorphine within 30 days of Dosing Day 1 (patients who stopped apomorphine for reasons other than lack of efficacy OR tolerability issues may be considered for the trial).
• Female who is pregnant or lactating.
• Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite), or Tigan®.
• Participation in any other clinical trial within 14 days of the screening visit.
• Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit.
• Currently taking, or likely to need to take at any time during the course of the study
• Currently taking dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects.
• Drug or alcohol dependency in the past 6 months.
• Clinically significant orthostatic hypotension.
• Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
• Clinically significant medical surgical or laboratory abnormality in the judgment of the investigator.
• Psychiatric disorder, including but not limited to dementia or any disorder that, in the opinion of the Investigator requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
• Dementia that precludes providing informed consent.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (4)

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

University of South Florida Parkinson's Disease and Movement Disorders Center

Tampa, Florida, 33613, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Apomorphine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Limitations and Caveats

Due to the 90-minute sampling estimate λz values or calculate AUCinf, AUCext, or half-life as stated in the protocol was not possible.No PK parameters were calculated for subjects with fewer than 4 quantifiable concentrations following BLQ imputation

Results Point of Contact

• Title: CNS Medical Director
• Organization: Sunovion Pharmaceuticals Inc.

clinicaltrialdisclosure@sunovion.com

866-503-6351

Study Officials

• CNS Medical Director

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 29, 2014
• Study Start: August 31, 2014
• Primary Completion: November 24, 2014
• Study Completion: November 24, 2014
• Last Updated: July 30, 2020
• Results First Posted: July 30, 2020

Record last verified: 2020-07

Locations

US (4)