The primary objective of the study as a whole (part A-C) is to assess the PK and safety of buccal apomorphine relative to registered apomorphine formulations (subcutaneous, sublingual). Secondary objectives are the characterization of the PK-AE…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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
Background summary
APORON is a novel formulation of apomorphine. Apomorphine is a registered drug
indicated for the treatment of off-periods in patients with Parkinson's
disease. Currently, apomorphine is often administered via subcutaneous
injections, which can cause pain, local injection site reactions and may be
difficult to use for patients when they are experiencing an off-period. APORON
is a highly concentrated apomorphine buccal spray formulation which is expected
to be easy and painless to self-administer and and has the same efficacy as the
subcutaneous injection or sublingual administration.
Study objective
The primary objective of the study as a whole (part A-C) is to assess the PK
and safety of buccal apomorphine relative to registered apomorphine
formulations (subcutaneous, sublingual). Secondary objectives are the
characterization of the PK-AE relationship, and to evaluate the
patient-reported efficacy of buccal apomorphine administration.
Study design
Part A is a single-centre, open label, cross-over study to characterize the PK
of apomorphine after buccal and subcutaneous administration in 12 patients with
Parkinson*s disease.
Part B is a single-centre, open-label comparative PK study evaluating an
improved buccal apomorphine formulation and an US-marketed apomorphine dual
film for sublingual administration (Kynmobi) in 12 patients with Parkinson*s
disease.
Part C is a single-centre, 12-week open label study to characterize the safety
and (local) tolerability of daily buccal apomorphine administration in 16-18
patients with Parkinson*s disease
Intervention
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) (dose based on data from part
A), 1 dose KYNMOBI 30 mg.
Part C: Buccal apomorphine spray (APORON) (dosage as used in part B)
Study burden and risks
Subjects will visit CHDR multiple times. During the study, several assessments
and activities will be performed, such as blood collection, measurement of
vital signs, ECGs, physical and neurological examinations and questionnaires.
Apomorphine is a well-known drug, so the risk of unexpected systemic side
effects is limited. Apomorphine can cause nausea, vomiting and orthostatic
hypotension, mainly in apomorphine-naive patients. To prevent these side
effects, patients in study part A and B are given 20 mg domperidone 3 times
daily starting 2 days prior to dosing and on dosing days. The patients in study
part A and B might become dyskinetic due to dosing with both their normal
Parkinson medication and subcutaneous or buccal apomorphine. To prevent this,
patients are allowed to skip or postpone their own medication as needed.
APORON might result in local side effects. Therefore, the buccal mucosa is
closely monitored throughout the study. After 2 mg buccal apomorphine
administration, both safety (adverse events) and PK data will be reviewed
before proceeding to a higher dose.
Kerkstraat 29
Casteren 5529 AK
NL
Kerkstraat 29
Casteren 5529 AK
NL
Listed location countries
Age
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
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003315-60-NL |
| CCMO | NL71179.056.20 |
| OMON | NL-OMON26898 |