Back to resultsA Study to Examine APL-130277 in Patients With Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
APL-130277
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Potential for lack of compliance and follow-up in the judgment of the investigator.
- 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.
- Previous neurosurgery for PD.
- Donation of blood or plasma in the 30 days prior to dosing.
- Presence of cankers or mouth sores.
Sites / Locations
- Banner Sun Health Research Institute
- Rocky Mountain Movement Disorders Center
- Parkinson's Disease and Movement Disorders Center of Boca Raton
- University of South Florida Parkinson's Disease and Movement Disorders Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
APL-130277
Arm Description
open label baseline comparison
Outcomes
Primary Outcome Measures
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).
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.
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.
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.
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).
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.
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.
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.
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).
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT02228590
First Posted
August 26, 2014
Last Updated
July 14, 2020
Sponsor
Sumitomo Pharma America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02228590
Brief Title
A Study to Examine APL-130277 in Patients With Parkinson's Disease
Official Title
A Phase 2 Study to Examine the Safety, Tolerability and Efficacy of APL-130277 in Patients With Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 31, 2014 (Actual)
Primary Completion Date
November 24, 2014 (Actual)
Study Completion Date
November 24, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma America, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APL-130277
Arm Type
Other
Arm Description
open label baseline comparison
Intervention Type
Drug
Intervention Name(s)
APL-130277
Other Intervention Name(s)
Apomorphine Hydrochloride, Sublingual Thin Film
Intervention Description
Apomorphine Hydrochloride, Sublingual Thin Film
Primary Outcome Measure Information:
Title
The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
Description
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).
Time Frame
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
Title
Time to 'ON' State From Time of Dosing of APL-130277
Description
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.
Time Frame
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
Title
Duration of 'ON' Response From Time of Dosing of APL-130277
Description
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.
Time Frame
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
Title
Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode
Description
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.
Time Frame
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
Title
Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
Description
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).
Time Frame
Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
Title
PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
Description
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.
Time Frame
Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
Title
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
Description
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.
Time Frame
Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
Title
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
Description
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.
Time Frame
Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
Title
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
Description
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).
Time Frame
Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
Secondary Outcome Measure Information:
Title
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Description
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.
Time Frame
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Potential for lack of compliance and follow-up in the judgment of the investigator.
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.
Previous neurosurgery for PD.
Donation of blood or plasma in the 30 days prior to dosing.
Presence of cankers or mouth sores.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
CNS Medical Director
Organizational Affiliation
Sumitomo Pharma America, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Banner Sun Health Research Institute
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
Rocky Mountain Movement Disorders Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Parkinson's Disease and Movement Disorders Center of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
University of South Florida Parkinson's Disease and Movement Disorders Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Examine APL-130277 in Patients With Parkinson's Disease
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