Phase 3
Completed N=141
Efficacy, Safety and Tolerability Study of APL-130277 for the Acute Treatment of OFF Episodes in Patients With Parkinson's Disease
Parkinson Disease, Off Episodes
Source: ClinicalTrials.gov NCT02469090 ↗
Enrolled (actual)
141
Serious AEs
1.6%
Results posted
Jul 2020
Primary outcomePrimary: Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12 — -3.5; -11.1 Units on a scale — p=0.0002
◆ Published Evidence
Highly cited
126citations · ~21 / year
Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study.
Summary
A 12-week, prospective, multi-center, randomized, double-blind, placebo controlled, Phase 3 study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to determine the efficacy, safety and tolerability of APL-130277.
Linked Publications
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Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12 |
-3.5; -11.1 | 0.0002 sig |
| SECONDARY Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes at MV4 - Week 12: Predicted Response Rate |
16; 35 | 0.0426 sig |
| SECONDARY Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes That Had a Duration of Effect of at Least 30 Minutes at MV4 - Week 12: Predicted Response Rate |
14; 31 | 0.0501 |
| SECONDARY Patient Global Impression of Improvement (PGI-I): Percentage of Patients Who Improved at MV4 - Week 12 |
20.0; 37.0 | — |
| SECONDARY Clinician Global Impression of Improvement (CGI-I): Percentage of Patients Who Improved at MV4 - Week 12 |
20.0; 40.7 | — |
| SECONDARY Mean Change From Screening Visit to MV4 (Week 12) in MDS-UPDRS Part II: Motor Aspects of Experience of Daily Living |
2.095; 0.995 | — |
| SECONDARY Mean Percentage of Instances Where a Full 'ON' Response Was Achieved at 30 Minutes Post-dose on the Home Dosing Diary Entries During the 2 Days Prior to MV4 - Week 12 |
31.10; 78.70 | — |
| SECONDARY Mean Change From Screening Visit to MV4 in the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Summary Index Score |
-1.671; 0.309 | — |
| SECONDARY Mean Change From Pre-Dose to 15 Minutes Post-Dose in the MDS-UPDRS Part III Score at MV4 - Week 12 |
-3.0; -6.4 | — |
| SECONDARY Time From Dosing to When Study Medication Provided an Effect at MV4 - Week 12 |
NA; 21.2 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female ≥ 18 years of age.
- Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.
- Clinically meaningful response to L-Dopa with well-defined early morning "OFF" episodes, as determined by the Investigator.
- Receiving stable doses of L-Dopa/carbidopa (immediate or CR) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit
- No planned medication change(s) or surgical intervention anticipated during the course of study.
- Patients must experience at least one well defined "OFF" episode per day with a total daily "OFF" time duration of ≥ 2 hours during the waking day, based on patient self-assessment.
- Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
- MMSE score > 25.
Exclusion Criteria
A patient will not be eligible for study entry if any of the following exclusion criteria are met:
- Atypical or secondary parkinsonism.
- Previous treatment with any of the following: a neurosurgical procedure for PD; continuous s.c. apomorphine infusion; or Duodopa/Duopa.
- Treatment with any form of s.c. apomorphine within 7 days prior to the initial Screening Visit (SV1). Patients that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
- Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN® (notably sodium metabisulfite); Tigan® (trimethobenzamide hydrochloride; patients from US sites only); or domperidone (patients from non-US sites only).
- Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1).
- Currently taking selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents.
- Drug or alcohol dependency in the past 12 months.
- History of malignant melanoma.
- Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
- Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
- History of clinically significant hallucinations during the past 6 months.
- History of clinically significant impulse control disorder(s).
- Dementia that precludes providing informed consent or would interfere with participation in the study.
Data sourced from ClinicalTrials.gov (NCT02469090) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.