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

A Phase 2 Study to Examine the Safety, Tolerability and Efficacy of APL-130277 in Patients With Parkinson's Disease

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)

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: APL-130277

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Tampa, Florida, United States, 33613
      • University of South Florida Parkinson's Disease and Movement Disorders Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Atypical or secondary parkinsonism
2. Changes in L-dopa or other PD drug dosing regimens 4 weeks before the screening visit.
3. 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).
4. Female who is pregnant or lactating.
5. Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite), or Tigan®.
6. Participation in any other clinical trial within 14 days of the screening visit.
7. Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit.
8. Currently taking, or likely to need to take at any time during the course of the study
9. Currently taking dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects.
10. Drug or alcohol dependency in the past 6 months.
11. Clinically significant orthostatic hypotension.
12. Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
13. Clinically significant medical surgical or laboratory abnormality in the judgment of the investigator.
14. 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.
15. Dementia that precludes providing informed consent.
16. Potential for lack of compliance and follow-up in the judgment of the investigator.
17. Any other condition, current therapy, or prior therapy (within 30 days of the screening visit), which, in the opinion of the Investigator, would make the subject unsuitable for the study.
18. Previous neurosurgery for PD.
19. Donation of blood or plasma in the 30 days prior to dosing.
20. Presence of cankers or mouth sores.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: APL-130277; open label baseline comparison	Drug: APL-130277; Apomorphine Hydrochloride, Sublingual Thin Film; Other Names: Apomorphine Hydrochloride, Sublingual Thin Film

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment	The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.	At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2014
• Primary Completion (Actual): November 24, 2014
• Study Completion (Actual): November 24, 2014

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 27, 2014
• First Posted (Estimate): August 29, 2014

Study Record Updates

• Last Update Posted (Actual): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dopamine Agonists; Dopamine Agents; Emetics; Apomorphine
• Other Study ID Numbers: CTH-105