A multicenter, randomized, active-controlled, double-blind, double-dummy, parallel group clinical trial, investigating the efficacy, safety, and tolerability of continuous subcutaneous ND0612 infusion in comparison to oral IR-LD/CD in subjects with Parkinson*s disease experiencing motor fluctuations (BouNDless)
- Conditions
- movement diseaseNeurodegenerative movement disorder10028037
- Registration Number
- NL-OMON52856
- Lead Sponsor
- euroderm Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
1. Male and female subjects with PD of any race at least 30 years of age who
sign an Institutional Review Board/Ethics Committee-approved informed consent
form (ICF).
2. Parkinson*s disease diagnosis consistent with the UK Brain Bank Criteria.
3. Modified Hoehn and Yahr scale in *ON* stage <= 3.
4. Subjects must experience motor fluctuations and experience an average of at
least 2.5 hours daily (with a minimum of 2 hours every day) in the *OFF* state
during the waking hours as confirmed by an adequately completed *ON/OFF* diary
over 3 days.
5. Subject treatment should be at least 4 doses/day of LD/ Dopa Decarboxylase
Inhibition (DDI) (or at least 3 doses/day of extended release LD/DDI, e.g.,
Rytary) and at least 400 mg/day of LD, or equivalent according to the
conversion table, and, according to the Investigator*s judgement, the subject
experiences motor fluctuations that cannot be further improved by adjusting
anti-PD medications.
6. Subjects and/or study partners have no impediment that may prevent them from
operating the pump system.
7. Subjects and/or study partners must demonstrate ability to keep accurate
diary entries of PD symptoms (*ON/OFF* diaries) with at least 75% concordance
with the the Blinded Efficacy Rater by the end of the diary training session
during the Screening Period, including at least 1 *OFF* assessment.
8. Mini Mental State Examination (MMSE) score >= 24.
9. Female subjects must be surgically sterile (hysterectomy, bilateral
oophorectomy, or tubal ligation); postmenopausal (defined as cessation of
menses for at least 1 year); or willing to practice a highly effective method
of contraception. All female subjects must be non-lactating and not pregnant
and have a negative urine pregnancy test at Screening and at Enrollment (IR1
D1). Female subjects of childbearing potential must practice a highly effective
method of contraception (such methods include combined [estrogen and
progestogen containing] hormonal contraception associated with inhibition of
ovulation: oral / intravaginal; transdermal / progestogen-only hormonal
contraception associated with inhibition of ovulation: oral / injectable;
implantable / intrauterine device [IUD] / intrauterine hormone-releasing system
[IUS]/ bilateral tubal occlusion / vasectomized partner/ sexual abstinence)
from 1 month before Enrollment (IR D1 /V2) until 1 month after the last dose of
study treatment. Alternatively, true abstinence is acceptable when it is in
line with the subject*s preferred and usual lifestyle. If a subject is usually
not sexually active but becomes active, the subject and sexual partner must
comply with the contraceptive requirements detailed above.
10. Willingness and ability to comply with study requirements.
11. Subjects must have a named study partner that signed the ICF.
12. Approval for entry into the study by an independent EAC.
1. Atypical or secondary Parkinsonism.
2. Acute psychosis or troublesome hallucinations in the past 6 months.
3. Subjects with clinically significant or unstable medical, surgical, or
psychiatric condition or laboratory abnormalities which, in the opinion of the
Investigator or the EAC, represents a safety risk, makes the subject unsuitable
for study entry, or potentially unable to complete all aspects of the study.
4. Clinically significant ECG abnormalities.
5. Renal or liver dysfunction that may alter drug metabolism including
Screening Visit serum levels of creatinine > 1.5 mg/dL, aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 2 × upper limit of
normal, and total bilirubin > 2.5 mg/dL.
6. Any malignancy in the 5 years before enrollment, except basal cell carcinoma
of the skin, squamous cell carcinoma in situ, or cervical carcinoma in situ
that have been successfully treated.
7. Use of subcutaneous (SC) apomorphine injections, sublingual apomorphine, or
inhaled LD within 4 weeks before the enrollment.
8. Concomitant therapy or within 28 days before enrollment with:
metoclopramide, reserpine, methylphenidate, or amphetamines, well as
neuroleptics; exception in case of Quetiapine and Pimavanserin use: (1) allowed
only in case it had been used for a period of at least 3 months before
enrollment, (2) subject is on stable therapy for at least 3 months (3)
underlying psychosis to be under control and anticipating no changes to the
dosage of the medication throughout the study.
9. Subjects with a history of alcohol or substance abuse within the past 12
months.
10. Subjects who have taken experimental medications within 30 days before
enrollment.
11. Subjects who have previously participated in studies ND0612H-006 and/or
ND0612H-012.
12. Subjects who have previously undergone treatment for PD with a surgical
intervention (e.g., pallidotomy, thalamotomy, transplantation, deep brain
stimulation procedures), gene therapy, Duodopa®/Duopa®, or continuous
dopaminergic or apomorphine infusion. Subjects who have discontinued Duodopa®/
Duopa® treatment at least 6 months before enrollment and have undergone stoma
closure surgery at least 6 months before enrollment, may be included in this
study. Subjects who are planning to undergo treatment for PD with a surgical
intervention will be enrolled at the Investigator*s discretion.
13. Subjects with severe disabling dyskinesias, based on Investigator's
discretion.
14. History of significant skin conditions or disorders (e.g., psoriasis,
atopic dermatitis, etc.) or evidence of different lesions (e.g., sunburn, acne,
scar tissue, tattoo, open wound, branding, or pigmentation) that, in the
Investigator's opinion, would interfere with the infusion of the study drug or
could interfere with study assessments.
15. Subjects who do not have sufficient SC tissue for SC infusion treatment.
16. Use of non-selective monoamine oxidase inhibitors (e.g., phenelzine,
isocarboxazid, tranylcypromine) within 4 weeks before enrollment.
17. Use of monoamine-depleting agents (e.g., reserpine, tetrabenazine,
deutetrabenazine, valbenazine, xenazine) within 4 weeks before enrollment.
18. Current or previous diagnosis of Dopamine Dysregulation Syndrome or Impulse
Control Disorder.
19. Impulse control disorder within the pa
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>DBDD Maintenance Period (DB W12) in the mean daily ON time without<br /><br>troublesome dyskinesia (GOOD ON) adjusted to subject's waking hours and<br /><br>normalized to 16 waking hours, based on subject's ON/OFF diary assessments on<br /><br>the 3 consecutive days before the visit.<br /><br>GOOD ON is defined as the sum of ON time without dyskinesia and ON time<br /><br>with non-troublesome dyskinesia.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary efficacy endpoint is the change from Baseline to the end of<br /><br>the DBDD Maintenance Period (DB W12) in the mean daily OFF<br /><br>time adjusted to subject's waking hours and normalized to 16 waking hours,<br /><br>based on subject's ON/OFF diary assessments on the 3 consecutive days before<br /><br>the visits.</p><br>