- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00145171
A Sub-Study With Patients in APO401 to Evaluate Adverse Events During Dose Introduction in Apomorphine-naïve Patients.
Study of Orthostatic Changes Upon Apomorphine Dose Initiation in Late Stage Parkinson's Disease Patients. A Dose Escalation Study With a Double-Blind Placebo-Controlled Efficacy Determination at 4 Mg.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The primary objective of this study was to determine the electrocardiographic and orthostatic effects of apomorphine during controlled in-patient dose introduction in apomorphine-naïve late stage Parkinson's disease patients. Although safety observations represented the primary objective of the study, a control group was considered essential to properly interpret adverse events that occurred during dose titration. Additional data comparing the efficacy and safety of subcutaneous apomorphine, placebo and standard antiparkinson (anti-PD) therapy was derived from this experience.
This was a two-phase study that involved a controlled in-office dose titration phase followed by a 6-month outpatient open-label treatment phase. During the in-patient dose titration phase, subjects were evaluated on separate days for the response to single doses of medication administered during an observed "Off" event (defined as first "Off" event that occurs at least one hour after administration of the normal morning dose of oral antiparkinson medication). Evaluation of the acute response to oral anti-PD medication (Baseline) and to apomorphine dose escalation between 2 and 10 mg (Titration Visits) was conducted under unblinded conditions. At the 0.4-mL titration level, placebo was randomly introduced under double-blind crossover conditions.
Study Type
Enrollment
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age: Adults of any age > 18.
Sex: Men and non-pregnant, non-lactating women.
- Women of childbearing potential must have had a negative serum (Beta HCG) pregnancy test within 14 days of the study start.
- Women of childbearing potential must have used an acceptable form of contraception
- Patients with a clinical diagnosis of idiopathic Parkinson's disease, ie. not induced by drugs or caused by other diseases.
- Patients classified as stage II - V of the Hoehn and Yahr scale for staging the severity of Parkinson's disease (Appendix 16.1.12.3).
Patients with refractory motor fluctuations of any frequency or duration. These included but are not necessarily limited to patients with the following symptoms:
- Immobility resulting from regular dose failures.
- Severe "Off" period discomfort.
- Nocturnal/early morning dystonias.
- Voiding dysfunctions.
- Swallowing difficulties associated with "Off" periods.
- "Off" period visual hallucinations.
- Severe biphasic dyskinesia.
- Unless otherwise specified, enrolled patients must be on an optimally maximized oral therapy regimen. Optimized oral anti-PD medication included: levodopa/carbidopa in either immediate or delayed release forms, plus at least one other antiparkinson medication, which could include a direct acting oral dopamine agonist, a monoamine oxidase inhibitor (MAOB), or a catechol-O-methyltransferase inhibitor (COMT) for at least 30 days prior to enrollment into study.
- Patients enrolled in APO401 who have completed initial baseline observations, but have not received apomorphine therapy as part of the APO401 protocol or at any other point in time.
Exclusion Criteria:
- Patients with prior exposure to apomorphine, including prior participation in a Mylan sponsored study of subcutaneous apomorphine. Patients were enrolled in APO401 concurrently with APO303.
- Patients who did not conform to all of the above inclusion criteria.
- Patients under medical therapy for clinically significant psychoses or dementia.
- Patients with a history of drug or alcohol dependency within one year prior to study enrollment.
- Patients with unstable and clinically significant disease of cardiovascular (including orthostatic hypotension), hematologic (including Coombs' positive hemolytic anemia), hepatic, renal, metabolic, respiratory, gastrointestinal or endocrinological systems or neoplasm within the three months before the start of the study.
- Patients on methyldopa therapy.
- Patients with a history of true allergy to morphine or its derivatives, sulfur, sulfur containing medication, sulfites, trimethobenzamide or other anticholinergics.
- Patients treated with other experimental agents within 30 days before study entry.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Entire Study:
|
Adverse event assessments
|
For Crossover portion of placebo-controlled 4mg dose comparison:
|
Change in Unified Parkinson's Disease Rating Scale (UPDRS) at 20 minutes after dosing
|
Secondary Outcome Measures
Outcome Measure |
---|
1. Change in UPDRS Motor Score from pre-dose to 40 and 90 minutes after dosing;
|
2. Area under the curve (AUC) for UPDRS Motor Scores at 0, 20, 40 and 90 minutes;
|
3. Change in Dyskinesia Assessment at 0, 20, 40, and 90 minutes.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Will Sullivan, Mylan Bertek Pharmaceuticals
Study record dates
Study Major Dates
Study Start
Primary Completion
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- APO303
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Parkinson Disease
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedParkinson Disease 6, Early-Onset | Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human | Parkinson Disease Autosomal Recessive, Early Onset | Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1United States
-
ProgenaBiomeRecruitingParkinson Disease | Parkinsons Disease With Dementia | Parkinson-Dementia Syndrome | Parkinson Disease 2 | Parkinson Disease 3 | Parkinson Disease 4United States
-
King's College LondonGlaxoSmithKlineCompletedParkinson Disease | Idiopathic Parkinson Disease | Parkinson Disease, PARK8United Kingdom
-
Ohio State UniversityCompletedParkinson's Disease | Parkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease | Parkinson Disease, Idiopathic | Parkinson's Disease, IdiopathicUnited States
-
National Yang Ming UniversityUnknownEarly Onset Parkinson Disease | Early Stage Parkinson Disease
-
Michele Tagliati, MDRecruitingREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Cedars-Sinai Medical CenterEnrolling by invitationREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Mahatma Gandhi Institute of Medical SciencesCompletedStroke, Parkinson' s Disease, Neurological Impairments, Tele-rehabilitationIndia
-
Merck Sharp & Dohme LLCCompletedParkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease
-
University of DeustoCompletedPARKINSON DISEASE (Disorder)Spain
Clinical Trials on apomorphine HCl injection
-
Mylan Bertek PharmaceuticalsCompletedParkinson DiseaseUnited States
-
Mylan Bertek PharmaceuticalsCompleted
-
Mylan Bertek PharmaceuticalsCompletedParkinson DiseaseUnited Kingdom
-
TelikCompletedMyelodysplastic SyndromesUnited States
-
Suzhou Zelgen Biopharmaceuticals Co.,LtdRecruiting
-
TelikCompletedMultiple Myeloma | B Cell Lymphoma | Mantle Cell LymphomaUnited States
-
University Hospital, ToulouseFrench Parkinson AssociationCompletedParkinson's DiseaseFrance
-
Istanbul UniversityCompletedPain, PostoperativeTurkey
-
Juvabis AGInnovative Medicines InitiativeCompleted
-
Lumosa Therapeutics Co., Ltd.Completed