Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Apomorphine hydrochloride; Placebo
Intervention description: Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe; Sodium chloride 9 mg/ml
Intervention MeSH terms: Apomorphine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 107.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Parkinson's disease; motor fluctuations; not well controlled; medical treatment; apomorphine

Summary:

      The primary objective of the trial was to investigate the efficacy of apomorphine continuous
      subcutaneous infusion compared to placebo in Parkinson's Disease patients with motor
      fluctuations not well controlled on medical treatment.

      The secondary objective of the study was to investigate the safety and tolerability of
      apomorphine continuous subcutaneous therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients aged ≥30 years

          -  Diagnosis of idiopathic PD of >3 years' duration, defined by the UK Brain Bank
             criteria (with the exception of >1 affected relative being allowed), without any other
             known or suspected cause of Parkinsonism

          -  Hoehn & Yahr stage up to 3 in the ON and 2 to 5 in the OFF state

          -  Motor fluctuations not adequately controlled on medical treatment including levodopa
             which was judged by the treating physician to be optimal

          -  Average of OFF time > 3 hours/day based on screening and baseline diary entries with
             no day with < 2 hours of OFF time recorded

          -  Stable medication regimen, with a stable dose of levodopa administered in at least 4
             intakes, for at least 28 days prior to baseline. All oral or transdermal
             antiparkinsonian drugs were permitted, with the exception of budipine. This regimen
             might include the use of levodopa/DDCI rescue medication, if this occurred up to 2
             times a day, at doses of up to 200 mg levodopa/day

          -  Patients must be able to differentiate between the ON and OFF state and between
             troublesome and non-troublesome dyskinesias

          -  Male and female patients must be compliant with a highly effective contraceptive
             method (oral hormonal contraception alone is not considered highly effective and must
             be used in combination with a barrier method) during the study and for the 12-month
             OLP, if sexually active

          -  Females of childbearing potential must have a negative serum human chorionic
             gonadotropin (hCG) or urine pregnancy test at screening

          -  Ability to accurately complete a paper diary on designated days (with assistance from
             caregivers, if required), recording periods when they are "ON without troublesome
             dyskinesia", "ON with troublesome dyskinesia", OFF, and sleeping

          -  Written informed consent prior to enrolment, after being provided with detailed
             information about the nature, risks, and scope of the clinical trial as well as the
             expected desirable and adverse effects of the study treatments

          -  Patients considered reliable and capable of adhering to the protocol, visit schedule,
             and medication intake according to the judgment of the investigator

        Exclusion Criteria:

          -  History of respiratory depression

          -  Hypersensitivity to apomorphine or any excipients of the medicinal product

          -  High suspicion of other parkinsonian syndromes

          -  Presence of severe freezing or clinically relevant postural instability leading to
             falls during the ON state

          -  Concomitant therapy or within 28 days prior to baseline with: apomorphine pen
             injections; alpha-methyl dopa, metoclopramide, reserpine, neuroleptics,
             methylphenidate, or amphetamine; intrajejunal levodopa

          -  Previous use of apomorphine pump treatment

          -  History of deep brain stimulation or lesional surgery for PD

          -  Any medical condition that is likely to interfere with an adequate participation in
             the study, including e.g. current diagnosis of unstable epilepsy; clinically relevant
             cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months

          -  Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension

          -  Patients with a borderline QT interval corrected for heart rate according to Bazett's
             formula (QTcB) of >450 msec for male and >470 msec for female at screening or history
             of long QT syndrome; or >450 msec absolute duration

          -  Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, alanine
             transaminase [ALT] and aspartate transaminase [AST] >2 times the upper limit of
             normal)

          -  Clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL)

          -  Pregnant and breastfeeding women

          -  Clinically relevant cognitive decline, defined as MMSE ≤24 or according to Diagnostic
             and Statistical Manual of Mental Disorders (DSM) IV criteria for dementia

          -  Active psychosis or history of at least moderate psychosis in the past year, or with
             medically uncontrolled severe depression; very mild illusions or hallucinations in the
             sense of "feelings of passage or presence" with fully retained insight are not an
             exclusion criterion

          -  Known history of melanoma

          -  Any investigational therapy in the 4 weeks prior to randomization

          -  History or current drug or alcohol abuse or dependencies