Parkinson's Disease
Conditions
Interventions
Part A: 2 mg subcutaneous apomorphine (APO-go® 5 ml ampoules 10 mg/ml) and 3
doses of buccal apormorphine (APORON) (increasing doses, up to 8 mg)
Part B: 2 doses buccal apomorphine spray (APORON) (do
Sponsors
Criceto
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Part A and B 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. 6) Mini-Mental State Examination (MMSE) score >= 20 and assessed by the investigator or qualified designee as able to provide informed consent. Part 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 with recognizable OFF periods at least once per day.
Exclusion criteria
Exclusion criteria: Part A and B: 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 As in part A, but with the following differences: 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 prior to first dose, or history of long QT syndrome. 3) Contraindications to the excipients of the buccal or sublingual apomorphine formulation, or contraindications to domperidone. 12) Elevated hepatic panel, defined as serum levels of ALT, AST, GGT, ALP or TBL higher than 2 times the upper limit of normal. 19) Use of any apomorphine formulation in the 4 weeks prior to first dosing. 20) Use of 5HT3 antagonists. Part 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 |
|---|---|
| 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 * Apomorphine plasma concentrations (parameters as above, with the only change that in part B the ratio of buccal to sublingual AUC and Cmax will be calculated) * Treatment-emergent (serious) adverse events ((S)AEs). * Concomitant medication * Clinical laboratory tests o Haematology o Chemistry o Coagulation o Urinalysis * Vital signs o Pulse Rate (bpm) o Systolic blood pressure (mmHg) o Diastolic blood pressure (mmHg) o Orthostatic hypotension (delta mmHg sit-sta) o Respiratory rate (breaths/min) o Pulse oximetry (SpO2) (%) * ECG o Heart Rate (HR) (bpm), PR, QRS, QT, QTcF Primary part C - Treatment-emergent (S)AEs - Concomitant medication - Clinical laboratory tests (as above) - Vital signs (as above) - ECG (as above) - C-SSRS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Part A - Treatment-emergent (S)AEs - Concomitant medication - Clinical laboratory tests (as above) - Vital signs (as above) - ECG (as above) Secondary part B - Apomorphine plasma concentrations (parameters as above for part A) - Treatment-emergent (S)AEs Secondary part C - Percentage of patients in each response category (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 | — |
Countries
Netherlands
Outcome results
None listed