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)

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2018-004156-37-IT
• Date of registration: 17/06/2021
• Prospective Registration: No
• Primary sponsor: NEURODERM LTD.
• Public title: 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)
• Scientific title: 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) - BouNDless
• Date of first enrolment: 04/05/2020
• Target sample size: 482
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004156-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Czechia, France, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Russian Federation, Serbia, Slovakia, Spain, Sweden, Ukraine, United Kingdom, United States

Contacts

• Name: Galit Shaltiel-Gold,
• Affiliation: NeuroDerm Ltd.

• Name: Galit Shaltiel-Gold,
• Affiliation: NeuroDerm Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
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 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

Exclusion criteria:
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, excluding basal cell carcinoma of the skin 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), 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. Current Impulse Control Disorder in the last 5 years.
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 drug or placebo or any of their excipients.
22. History of narrow angle glaucoma


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: IR LD / CD
Product Name: Carbidopa and Levodopa tablets, USP
Product Code: [NA]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Current Sponsor code: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Current Sponsor code: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: levodopa/carbidopa solution
Product Code: [ND0612]
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Current Sponsor code: LEVODOPA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Current Sponsor code: CARBIDOPA
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 7500-
Pharmaceutical form of the placebo: Concentrate for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective of the study is to determine the effect of ND0612 on daily "ON" time without troublesome dyskinesia (defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia) using subject-completed "ON/OFF" diary assessments of motor function in subjects with Parkinson's disease (PD) experiencing motor fluctuations.

Secondary Objective: Key secondary objective of the study is to determine the effect of ND0612 on daily "OFF" time in subjects with PD experiencing motor fluctuations using subject-completed "ON/OFF" diary assessments of motor function.

Timepoint(s) of evaluation of this end point: End of the DBDD Maintenance Period (DB W12)

Primary end point(s): The primary endpoint is the change from Baseline to the end of the DBDD Maintenance Period (DB W12) in the mean duration of "ON" time without troublesome dyskinesia adjusted to subject's waking hours and normalized to 16 waking hours, based on subject's "ON/OFF" diary assessments on the 3 consecutive days before the visit. "ON" time without troublesome dyskinesia is defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: End of the DBDD Maintenance Period (DB W12)

Secondary end point(s): The key secondary efficacy endpoint is the change from Baseline to the end of the DBDD Maintenance Period (DB W12) in the mean duration (hours) of "OFF" time adjusted to subject's waking hours and normalized to 16 waking hours, based on subject's "ON/OFF" diary assessments on the 3 consecutive days before the visits.

Secondary ID(s)

2018-004156-37-SE

ND0612-317

Source(s) of Monetary Support

NeuroDerm Ltd.

Ethics review

Status: Approved
Approval date: 22/01/2020
Contact: