A Study That Compares the Extent to Which Apomorphine Becomes Available in the Body After Taking Either an Investigational Drug Containing Apomorphine or Apomorphine That is Injected Under the Skin in People With PD Complicated by "OFF" Episodes
A Comparative Bioavailability Study to Evaluate the Single Dose Pharmacokinetic Properties of APL-130277 With Two Different Formulations of Subcutaneous Apomorphine in a Randomized, 3-Period Crossover Design in Subjects With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Boca Raton, Florida, United States, 33486
- Parkinson's Disease and Movement Disorders Center of Boca Raton
-
Port Charlotte, Florida, United States, 33980
- Parkinson's Disese Treatment Center of SW Florida
-
-
Michigan
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Farmington Hills, Michigan, United States, 48334
- Quest Research Institute
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female ≥ 18 years of age.
- Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
- Clinically meaningful response to Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.
- Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.
- Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the Screening Visit. Adjunctive PD medication regimens must be maintained at a stable dose for at least 4 weeks prior to the Screening Visit with the exception that MAOB inhibitors must be maintained at a stable level for at least 8 weeks prior to the Screening Visit.
- No planned medication change(s) or surgical intervention anticipated during the course of study.
- Patients must experience a well-defined "OFF" episode in the morning if they do not take their morning PD medications on schedule, and must be willing to delay morning doses on the 3 study dosing days
- Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
- Mini-Mental State Examination (MMSE) score > 23.
If female and of childbearing potential, must agree to use one of the following methods of birth control:
- Oral contraceptive;
- Contraceptive patch;
- Barrier (diaphragm, sponge or condom) plus spermicidal preparations;
- Intrauterine contraceptive system;
- Levonorgestrel implant;
- Medroxyprogesterone acetate contraceptive injection;
- Complete abstinence from sexual intercourse;
- Hormonal vaginal contraceptive ring; or
- Surgical sterilization or partner sterile (must have documented proof).
- Male patients must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) or maintain a monogamous relationship with a person who is not of child-bearing potential from first study drug administration until 30days after final drug administration.
- 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.
- Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
- Contraindications to APO-go® or APOKYN® or hypersensitivity to apomorphine hydrochloride or any marcrolide antibiotic or any of the ingredients APO-go® or APOKYN® (notably sodium metabisulfite).
- Female who is pregnant or lactating.
- Participation in a clinical trial within 30 days prior to the Screening Visit.
- Receipt of any investigational (ie, unapproved) medication within 30 days prior to the Screening Visit.
- Any selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and clozapine) or dopamine depleting agents within 30 days prior to the Screening Visit.
- Drug or alcohol dependency in the past 12 months.
- History of malignant melanoma.
- Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
- Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
- History of clinically significant hallucinations during the past 6 months.
- History of clinically significant impulse control disorder(s).
- Dementia that precludes providing informed consent or would interfere with participation in the study.
- Current suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
- Donation of blood plasma in the 30 days prior to first dosing.
- Cankers or mouth sores within 30 days prior to the Screening Visit, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a patient into the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: APL-130277, sublingual thin film
APL-130277, sublingual thin film, once daily
|
APL-130277 sublingual thin film
Other Names:
|
|
Active Comparator: Subcutaneous APO-go
Subcutaneous APO-go, once daily
|
Subcutaneous APO-go
Other Names:
|
|
Active Comparator: Subcutaneous APOKYN
Subcutaneous APOKYN, once daily
|
Subcutaneous APOKYN
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Day 1
|
Dose normalized maximum observed plasma concentration (Cmax)
|
Day 1
|
|
Observed Time of the Maximum Concentration (Tmax)
Time Frame: Day 1
|
Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.
|
Day 1
|
|
Area Under the Concentration- Time Curve (AUC Last)
Time Frame: Day 1
|
area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.
|
Day 1
|
|
Area Under the Concentration- Time Curve (AUC Inf)
Time Frame: Day 1
|
area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.
|
Day 1
|
|
Mean Residence Time (MRT)
Time Frame: Day 1
|
Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf.
AUMCinf is the area under the first moment (time.plasma
concentration vs. time) curve.
|
Day 1
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
Time Frame: Day 1
|
Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.
|
Day 1
|
|
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
Time Frame: Day 1
|
Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.
|
Day 1
|
|
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
Time Frame: Day 1
|
Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf * λz).
|
Day 1
|
|
Terminal-phase Half-life (t½)
Time Frame: Day 1
|
Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
|
Day 1
|
|
Terminal-phase Rate Constant ( λz)
Time Frame: Day 1
|
Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase.
At least 3 data points in the terminal phase will be used in the determination of the rate constant.
|
Day 1
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
Time Frame: Day 1
|
Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.
|
Day 1
|
Collaborators and Investigators
Sponsor
Sponsor
Investigators
Investigators
- Study Chair: CNS Mecdical Director, Sunovion Pharmacetuicals Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
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
Other Study ID Numbers
- CTH-203
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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