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Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease (TOLEDO)

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ClinicalTrials.gov Identifier: NCT02006121
Recruitment Status : Unknown
Verified August 2016 by Britannia Pharmaceuticals Ltd..
Recruitment status was:  Active, not recruiting
First Posted : December 9, 2013
Last Update Posted : August 11, 2016
Sponsor:
Information provided by (Responsible Party):
Britannia Pharmaceuticals Ltd.

Brief Summary:

The main purpose of this study is to investigate the efficacy of apomorphine subcutaneous infusion compared to placebo in advanced Parkinson's Disease patients.

The secondary purpose of this study is to investigate the safety and tolerability of apomorphine subcutaneous therapy.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: Apomorphine hydrochloride Drug: Placebo Phase 3

Detailed Description:

- Primary efficacy variable is the absolute change in time spent "OFF" from baseline to the end of 12 weeks treatment period based on patient diaries

Secondary Endpoints:

  • Percentage of patients with response to therapy, defined as an OFF time reduction of at least 2 hours, from baseline to end of 12 weeks treatment period
  • Patient Global Impression of Change
  • Absolute Change in time spent "ON without troublesome dyskinesia"
  • Change in oral L-dopa and L-dopa equivalent dose
  • Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III motor examination) during ON periods
  • Change in Quality of Life (using PDQ-8)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter,Parallel-group,Double-blind,Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Apomorphine sc Infusion in Parkinson's Disease Patients With Motor Complications Not Well Controlled on Medical Treatment
Study Start Date : December 2013
Actual Primary Completion Date : June 2016
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Apomorphine hydrochloride
Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe
Drug: Apomorphine hydrochloride
Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe
Other Name: Apo-go

Placebo Comparator: Placebo
Placebo: saline infusion
Drug: Placebo
Sodium chloride 9 mg/ml




Primary Outcome Measures :
  1. Absolute change in time spent "OFF" from baseline to the end of 12 weeks treatment period based on patient diaries [ Time Frame: after 12 weeks of treatment ]

Secondary Outcome Measures :
  1. Evaluation of adverse events and local tolerability [ Time Frame: 1 year ]
    The safety parameters will be summarized by treatment group

  2. Skin changes [ Time Frame: 1 year ]
    The safety parameters will be summarized by treatment group

  3. Full blood count [ Time Frame: 1 year ]
  4. Epworth Sleepiness Scale [ Time Frame: 1 year ]
  5. Questionnaire for Impulsive-Compulsive Disorders in Parkinson`s Disease [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Male or female patients aged ≥30

  • Diagnosis of idiopathic Parkinson's disease 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 L-dopa which was judged to be optimal by the treating physician
  • Average of OFF time>= 3 h/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 L-dopa administered in at least 4 intakes, for at least 28 days prior to baseline. All oral or transdermal antiparkinsonian drugs are permitted, with the exception of budipine. This regimen may include the use of L-dopa /DDCI rescue medication if this occurs up to 2 times a day, at doses of up to 200 mg L-dopa/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 9 months long-term follow-up period, if sexually active
  • Females of childbearing potential must have a negative serum hCG 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:

  • 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 L-dopa
  • 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 (QTc) of >450 ms for male and >470 ms for female at Screening or history of long QT syndrome; or >450 ms absolute duration
  • Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, ALT and 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02006121


Locations
Austria
Donauspital
Vienna, Austria, 1220
Sponsors and Collaborators
Britannia Pharmaceuticals Ltd.
Investigators
Principal Investigator: Regina Katzenschlager, Doz. Dr. Donauspital KH SMZ Ost, Neurologie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Britannia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT02006121     History of Changes
Other Study ID Numbers: CT-37527-13-0124
2013-000980-10 ( EudraCT Number )
First Posted: December 9, 2013    Key Record Dates
Last Update Posted: August 11, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Britannia Pharmaceuticals Ltd.:
Parkinson's disease
motor fluctuations
not well controlled
medical treatment

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Apomorphine
Emetics
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action