Clinical Trials Register

Summary
EudraCT Number:	2015-005078-39
Sponsor's Protocol Code Number:	ND0612H-006
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2015-005078-39

A.3

Full title of the trial

A multicenter, parallel-group, rater-blinded, randomized clinical study investigating the efficacy, safety, tolerability and pharmacokinetics of 2 dosing regimens of ND0612H, a solution of levodopa/carbidopa delivered via a pump system as a continuous subcutaneous infusion in subjects with advanced Parkinson's disease

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

ND0612H-006

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NeuroDerm Ltd.
B.1.3.4	Country	Israel
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	NeuroDerm Ltd.
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NeuroDerm Ltd.
B.5.2	Functional name of contact point	Yael Ullmann
B.5.3	Address:
B.5.3.1	Street Address	Ruhrberg Science building - Bell entrance - 5th floor - 3 Pekeris St.
B.5.3.2	Town/ city	Rehovot
B.5.3.3	Post code	7670212
B.5.3.4	Country	Israel
B.5.4	Telephone number	+972-8-9462729
B.5.5	Fax number	+972-8-9461729
B.5.6	E-mail	ullmann.y@neuroderm.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	levodopa/carbidopa solution
D.3.2	Product code	ND0612
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levodopa
D.3.9.1	CAS number	59-92-7
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	LEVODOPA
D.3.9.4	EV Substance Code	SUB08468MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carbidopa
D.3.9.1	CAS number	38821-49-7
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	CARBIDOPA
D.3.9.4	EV Substance Code	SUB06126MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	7.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with advanced Parkinson's disease

E.1.1.1

Medical condition in easily understood language

Parkinson's disease

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10061536
E.1.2	Term	Parkinson's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on daily “OFF” time

E.2.2

Secondary objectives of the trial

* To assess the difference between the 2 continuous SC infusion dosing regimens of ND0612H vs. standard oral LD/DDI (Dopa Decarboxylase Inhibitor) treatment on ability to induce early morning full “ON”
* To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on daily “ON” time without dyskinesia and “ON” time with dyskinesia (mild, moderate and severe).
* To assess the effect of continuous SC infusion of 2 dosing regimens of ND0612H on the motor score and activities of daily living scores of the Unified PD Rating Scale in comparison to standard oral LD/DDI treatment.
* To assess the Clinical Global Impression , Parkinson’s Disease Sleep Scale, and 39-Item PD Quality of Life [QoL] Questionnaire.
* To determine the need for rescue doses/dose modifications/additional therapy of standard oral LD/CD Immediate Release and/or entacapone.
* To profile the pharmacokinetics of 2 dosing regimens of ND0612H compared to the subject’s standard oral LD/DDI dose.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
2. PD diagnosis consistent with the UK Brain Bank Criteria.
3. Modified Hoehn & Yahr scale in “ON” state of stage ≤3.
4. Taking at least 4 doses/day of LD (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least 2 other classes of anti-PD medications in a therapeutic dose for at least 30 consecutive days each.
5. Subjects must be stable on their anti-PD medication for at least 30 days before Day 1.
6. Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612H treatment period.
7. Must have a minimum of 2.5 hrs of “OFF” time per day with predictable early morning “OFF” periods as estimated by the subject.
8. Must have predictable and well defined early morning “OFF” periods with a good response to LD for treatment of the early morning “OFF” in the judgement of the investigator.
9. Mini Mental State Examination (MMSE) score >26.
10. No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.
11. 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 participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, a barrier method of birth control [e.g., condoms with contraceptive foams, diaphragms with contraceptive jelly], intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug.
12. Willingness and ability to comply with study requirements.
13. Subjects should have a study partner.

E.4

Principal exclusion criteria

1. Atypical or secondary parkinsonism.
2. Acute psychosis or hallucinations in past 6 months.
3. Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator or the eligibility reviewer, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
4. Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated).
5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit.
6. Prior neurosurgical procedure for PD, or duodopa treatment.
7. Subjects with a history of drug abuse or alcoholism within the past 12 months.
8. Clinically significant ECG rhythm abnormalities.
9. Renal or liver dysfunction that may alter drug metabolism including: serum creatinine >1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN), total serum bilirubin >2.5 mg/dL.
10. Subjects who are not willing to operate the pump system.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change from baseline to Day 28 in daily “OFF” time (i.e. the phase with no response to medication and significant motor symptoms) as assessed by a blinded rater

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

E.5.2

Secondary end point(s)

The key secondary efficacy endpoint is the percentage of subjects with full “ON” (i.e. an “ON” response comparable to the “ON” response to standard oral LD/DDI treatment) at approximately 08:00 and approximately 09:00 on Day 28, as determined by the subject and the blinded rater separately.

The other secondary endpoints are:
• Change from baseline to Day 28 in daily “ON” time without dyskinesia and “ON” time with dyskinesia (mild, moderate, severe) as assessed by a blinded rater, with “ON” time defined as phase
with good response to medication and few symptoms.
• Change from baseline to Day 28 in UPDRS part III (motor) scores, at 4 and 8 hrs post dose/infusion start
• Change from baseline to Day 28 in UPDRS part II (ADL) scores
• CGI-Improvement (CGI-I) score on Day 28 and change from baseline to Day 28 in CGI-Severity (CGI-S) score as assessed by investigator
• Change from baseline to Day 27 in PDSS total score
• Change from baseline to Day 27 in PDQ-39 summary index and the 8 dimension scores
• Need for supplemental oral LD/CD and/or entacapone during the outpatient period
• Pharmacokinetics at 2 time points

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 27 and Day 28

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

rater-blinded study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

2 dosages of IMP will be studied: Regimen 1 (720mg LD/90mg CD) vs Regimen 2 (537.6mg LD/67.2mg CD)

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Germany

Israel

Italy

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects would just revert to normal standard of care or will enter in the open label study

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-05-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-01-31

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