The current protocol is designed to satisfy the need for a compassionate use treatment
protocol as well as for a long-term open label follow-up study.
The primary objective of APO401 was to gain additional safety data in the outpatient use of
apomorphine. APO401 provided an opportunity for all patients who had participated in a
Mylan-sponsored placebo controlled trial of apomorphine to receive apomorphine therapy as
ambulatory outpatients. Patients other than those enrolled in a Mylan-sponsored study were
allowed to participate. Additional data regarding the safety and effectiveness of
outpatient use of subcutaneous apomorphine were derived from this experience.
- Prior participation in a MYLAN sponsored study of subcutaneous apomorphine
administration for the treatment of Off episodes due to end-of-dose motor
deterioration ("Wearing-Off" effect) or sudden loss of mobility at seemingly random
intervals ("On-Off" effect). With prior approval from MYLAN, patients other than
those enrolled in a MYLAN sponsored study were allowed to participate. Following
approval of Amendment 01, patients who met all other criteria for inclusion,
regardless of previous participation in an apomorphine study, were allowed to
- 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, i.e., 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.
- Patients with refractory motor fluctuations of any frequency or duration. These
include 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.
- The patient (or a caregiver) had to be able to recognize an Off state, and be
sufficiently motivated to learn how to use the apomorphine injection to control these
- The patient (or a caregiver) had to be able to maintain On-Off diaries.
- 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 direct acting oral
dopamine agonist for at least 30 days prior to enrollment into study.
- Patients under medical therapy for clinically significant psychoses or dementia not
related to ingestion of anti-PD medications. (Patients with hallucinations or other
central adverse reactions associated solely with anti-PD medications were not
- Patients with a history of drug or alcohol dependency within one year prior to study
- 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
- Patients with a history of true allergy to morphine or its derivatives (including
apomorphine), sulfur, sulfur containing medication, sulfites, sulfates, Tigan(R)
- Patients treated with experimental agents (other than apomorphine intermittent
subcutaneous injections) within 30 days before study entry. Patients with
participation in Bertek-sponsored study APO202 were excluded from participation in
- Patients whose apomorphine regimen was characterized by administration methods other
than intermittent subcutaneous injection.
- Patients who could not or would not sign an Informed Consent form.