Parkinson's Disease MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Apo-go
Product Name: APO-go®
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Apomorphine
CAS Number: 41372-20-7
Current Sponsor code: APO-go
Other descriptive n
Sponsors
Criceto IKM B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A 1) Male or female, 30-85 years of age, inclusive at screening. 4) Clinical diagnosis (confirmed by a neurologist) of Parkinson’s disease and classified by the investigator as Hoehn and Yahr stage I to IV in the ON state. 5) Having clear, self-described motor fluctuations as assessed by the 9-symptom Wearing-off Questionnaire (WOQ-9): at least one motor symptom (Question 1, 2, 4, 6, 9) indicated to improve after the subject’s next anti-Parkinson medication dose. 6) Mini-Mental State Examination (MMSE) score = 20 and assessed by the investigator or qualified designee as able to provide informed consent. Part B and C 1) Male or female, 30-85 years of age, inclusive at screening. 4) Clinical diagnosis (confirmed by a neurologist) of Parkinson’s disease and classified by the investigator as Hoehn and Yahr stage I to III in the ON state. 5) Mini-Mental State Examination (MMSE) score = 20 and assessed by the investigator or qualified designee as able to provide informed consent. 8) On a stable dose of 1 to 4 mg subcutaneous apomorphine (APO-GO PEN) for the management of OFF episodes for at least 4 weeks prior to first study drug administration. 9) Subject’s at-home subcutaneous apomorphine injection location is the abdomen. 11) Subjects who experience motor fluctuations (as assessed by the 9-symptom Wearing-off Questionnaire (WOQ-9): at least one motor symptom (Question 1, 2, 4, 6, 9) indicated to improve after the subject’s next anti-Parkinson medication dose) with recognizable OFF periods at least once per day. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 23 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: Part A: 1) Atypical or secondary parkinsonism e.g., multiple-system atrophy or progressive supranuclear palsy, or evidence of drug-induced parkinsonism. 2) Subjects with a borderline QT interval corrected for heart rate according to Fridericia's formula (QTcF) of >450 ms for male and >470 ms for female, PR interval > 220 msec or QRS duration > 120 msec at screening or history of long QT syndrome. 6) Currently taking medication that can influence the efficacy of apomorphine in the opinion of the investigator, such as dopamine antagonists and dopamine depleting drugs, with the exception of domperidone. Part B and C: 1) Atypical or secondary parkinsonism e.g., multiple-system atrophy or progressive supranuclear palsy, or evidence of drug-induced parkinsonism. 2) Subjects with a borderline QT interval corrected for heart rate according to Fridericia’s formula (QTcF) of >450 ms for male and >470 ms for female, PR interval > 220 msec or QRS duration > 120 msec at screening or history of long QT syndrome. 4) Use of apomorphine formulations other than subcutaneous injections in the 4 weeks prior to first dosing. 7) Currently taking medication that can influence the efficacy of apomorphine in the opinion of the investigator, such as dopamine antagonists and dopamine depleting drugs, with the exception of domperidone.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study consists of 3 different parts, Part A, Part B and Part C. The main objective of the study is to determine the pharmacokinetics, (local) tolerability and efficacy of a buccal apormorphine spray (APORON) and compare it with a subcutaneous apomorphine injection and placebo. ;Secondary Objective: - Characterize the PK-PD relationship of buccal and subcutaneous apomorphine administration. - Characterize the occurrence of AEs (e.g. dyskinesia, nausea) in relation to apomorphine plasma concentrations after buccal and subcutaneous administration. - Patient preference for buccal or subcutaneous administration. - Patient-reported efficacy (within 30 minutes) of buccal apomorphine administration. - Asses the ratio between the self-chosen, at-home buccal apomorphine dose used during the study and the subcutaneous apomorphine dose used prior to the study ;Primary end point(s): Primary part A -Apomorphine plasma concentrations o Derived parameters including but not limited to Cmax, Tmax, Tlag, T1/2, AUC, relative bioavailability o Dose-normalized AUC and Cmax o Ratio of buccal to subcutaneous AUC and Cmax Primary part B • Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III o Change from baseline in MDS-UPDRS part III of apomorphine compared to placebo o 90% confidence interval of the estimated difference in change from baseline MDS-UPDRS part III between buccal and subcutaneous apomorphine o Number of responders based on = 7 points improvement of MDS-UPDRS part III • Disease State Assessment by physician (5 categories: ‘on’ with disabling dyskinesia, ‘on’ with non-disabling dyskinesia, ‘on’ state with no dyskinesia and normal motor function, partial ‘on’ state and ‘off’ state). o Number and percentage of patients turning ON o Number and percentage of patients ON at each time point • Patient ON/OFF assessment (3 categories: OFF, partial ON, full ON) o Number and percentage of patients who achieved a full on respon | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Part A - Treatment-emergent (S)AEs - Concomitant medication - Clinical laboratory tests (as above) - Vital signs (as above) - ECG (as above) Secondary part C - Percentage of patients in each response category (refer to Appendix I: no improvement/ slight improvement /moderate improvement/ full ON response within 30 minutes after administration of buccal apomorphine) as based on interview by phone and on patient diaries. - Question during phone call which determines patient preference for buccal or subcutaneous administration. - Average buccal dose used in Part C of the study - Daily used subcutaneous dose in clinical practice before entering the study;Timepoint(s) of evaluation of this end point: from pre dose to end of treatment | — |
Countries
Netherlands
Outcome results
None listed