A clinical study to investigate the efficacy, safety, and tolerability of continuous subcutaneous ND0612 infusion in comparison to oral treatment in subjects with Parkinson’s disease (BouNDless)
- Conditions
- Parkinson's diseaseMedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-004156-37-SK
- Lead Sponsor
- euroDerm Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 482
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/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
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 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 (IR D1/ V2). 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.
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 207
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 275
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 past 2 years, if considered clinically significant by the investigator.
20. Subjects who answered yes to questions 4 or 5 of the C-SSRS
within the last 5 years.
21. Known allergy to the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method