A Sub-Study With Patients in APO401 to Evaluate Adverse Events During Dose Introduction in Apomorphine-naïve Patients.

• ClinicalTrials.gov Identifier: NCT00145171
• Recruitment Status: Completed
• First Posted: September 5, 2005
• Last Update Posted: September 5, 2005
• Sponsor: Mylan Bertek Pharmaceuticals
• Information provided by: Mylan Bertek Pharmaceuticals

Tracking Information

• First Submitted Date: September 2, 2005
• First Posted Date: September 5, 2005
• Last Update Posted Date: September 5, 2005
• Study Start Date: February 2001
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: September 2, 2005)

• 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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 2, 2005)

• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Sub-Study With Patients in APO401 to Evaluate Adverse Events During Dose Introduction in Apomorphine-naïve Patients.
• Official Title: 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.
• Brief Summary: APO303 is a sub-study of patients enrolled in APO401 (the long-term open label safety protocol) and was designed to evaluate adverse events, particularly blood pressure drops when standing up during first dose in patients who have not been exposed to apomorphine before.

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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson Disease
• Intervention: Drug: apomorphine HCl injection
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: September 2, 2005): 56
• Original Enrollment: Same as current
• Study Completion Date: August 2002
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

1. Age: Adults of any age > 18.

2. Sex: Men and non-pregnant, non-lactating women.

   1. Women of childbearing potential must have had a negative serum (Beta HCG) pregnancy test within 14 days of the study start.
   2. Women of childbearing potential must have used an acceptable form of contraception
3. Patients with a clinical diagnosis of idiopathic Parkinson's disease, ie. not induced by drugs or caused by other diseases.
4. 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).

5. Patients with refractory motor fluctuations of any frequency or duration. These included but are not necessarily limited to patients with the following symptoms:

   1. Immobility resulting from regular dose failures.
   2. Severe "Off" period discomfort.
   3. Nocturnal/early morning dystonias.
   4. Voiding dysfunctions.
   5. Swallowing difficulties associated with "Off" periods.
   6. "Off" period visual hallucinations.
   7. Severe biphasic dyskinesia.
6. 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.
7. 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:

1. 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.
2. Patients who did not conform to all of the above inclusion criteria.
3. Patients under medical therapy for clinically significant psychoses or dementia.
4. Patients with a history of drug or alcohol dependency within one year prior to study enrollment.
5. 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.
6. Patients on methyldopa therapy.
7. Patients with a history of true allergy to morphine or its derivatives, sulfur, sulfur containing medication, sulfites, trimethobenzamide or other anticholinergics.
8. Patients treated with other experimental agents within 30 days before study entry.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00145171
• Other Study ID Numbers: APO303
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Mylan Bertek Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Will Sullivan; Mylan Bertek Pharmaceuticals

• PRS Account: Mylan Bertek Pharmaceuticals
• Verification Date: November 2002