Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease (TOLEDO)
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|ClinicalTrials.gov Identifier: NCT02006121|
Recruitment Status : Completed
First Posted : December 9, 2013
Results First Posted : July 8, 2019
Last Update Posted : July 8, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Parkinson's Disease||Drug: Apomorphine hydrochloride Drug: Placebo||Phase 3|
The primary efficacy variable is the mean change in time spent "OFF" from baseline (start of blinded treatment) to the end of a 12 weeks' double-blind treatment period based on patient diaries. Patients recorded their motor symptoms in half-hour blocks as OFF, ON without dyskinesia, ON without troublesome dyskinesia, or sleeping using the Hauser Parkinson's Disease home diary.
Key secondary Endpoints (tested hierarchically):
- Change in time spent "ON without troublesome dyskinesia"
- Patient Global Impression of Change
- Percentage of patients with response to therapy, defined as a mean OFF time reduction of at least 2 hours
- Change in oral levodopa and levodopa equivalent dose
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||107 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Multicentre,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|
|Actual Study Start Date :||March 3, 2014|
|Actual Primary Completion Date :||June 6, 2016|
|Actual Study Completion Date :||June 8, 2017|
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
Sodium chloride 9 mg/ml
- Mean Change in Daily OFF Time From Baseline (Start of Blinded Treatment) to the End of Double-blind Phase (Visit 10) Based on Patient Diaries Using MMRM mITT Population [ Time Frame: Baseline and 12 weeks ]The least squares mean reduction (improvement) in OFF time as reported by the patient using the Hauser Parkinson's disease home diary. Patients categorised their motor symptoms into OFF, ON with dyskinesia, ON without troublesome dyskinesia or sleeping using half hour blocks over 24 hours. Daily OFF time was computed from the average of valid motor diaries from the two days preceding each visit. Correct diary completion was evaluated during screening and observed by the investigator to ensure patients could categorise their motor symptoms correctly. A diary was considered valid if no more than 4 half-hour periods were either absent or duplicated. There were no invalid diaries at Baseline or Week 12.
- Mean Change in Daily Time Spent "ON Without Troublesome Dyskinesia" From Baseline to the End of the Double-blind Phase (Visit 10), Based on Patient Diaries Using MMRM mITT Population [ Time Frame: Baseline and 12 weeks ]The least squares mean change in "ON time without troublesome dyskinesia" as reported by the patient using the Hauser Parkinson's disease home diary. Each half hour of the day categorised as OFF, ON with dyskinesia, ON without troublesome dyskinesia or asleep. "ON time without troublesome dyskinesia" measures good ON time for a Parkinson's disease patient.
- Patient Global Impression of Change (PGIC), Using the mITT Population [ Time Frame: Baseline and 12 weeks ]PGIC is a self-administered questionnaire measuring personal general state of health on a 7-point rating scale. The 7 ordinal categories from which patients must choose are 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse. Results are presented as the % of patients who reported at least minimal improvement in general health status at week 12 compared to Baseline. A Wilcoxon range sum test was performed to test for treatment differences from baseline to end of 12 weeks' treatment period.
- Mean Change in Oral Levodopa Dose From Baseline to Visit 10 Using MMRM for the mITT Population [ Time Frame: Baseline and 12 weeks ]The least squares mean change in oral levodopa dose from Baseline to Visit 10 (week 12) was calculated excluding 3 centres who declined to participate in collecting the necessary details of PRN use of levodopa.
- Mean Change in Levodopa Equivalent Dose From Baseline to Visit 10 (Week 12) Using MMRM in the mITT Population [ Time Frame: Baseline and 12 weeks ]Levodopa equivalent dose is an indication of the burden of medication taken to control symptoms of Parkinson's disease with all medications other than levodopa itself being converted to a calculated levodopa dose using the methodology published by Tomlinson et al, 2010. The computation of LED excludes the study drug.
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
|Principal Investigator:||Regina Katzenschlager, Doz. Dr.||Donauspital KH SMZ Ost, Neurologie|