Clinical Trials Register

Summary
EudraCT Number:	2016-001403-23
Sponsor's Protocol Code Number:	M15-535
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-10-14
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Greece - EOF

A.2

EudraCT number

2016-001403-23

A.3

Full title of the trial

An Open-label, Randomized 12 Week Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects with Advanced Parkinson's Disease - DYSCOVER (DYSkinesia COmparative interventional trial on Duodopa VERsus oral medication)

Ανοικτή, Τυχαιοποιημένη Μελέτη 12 Εβδομάδων η Οποία Συγκρίνει την Αποτελεσματικότητα της Εντερικής Γέλης Λεβοντόπα-Καρβιντόπα/Εντερικού Εναιωρήματος Καρβιντόπα-Λεβοντόπα και της Βελτιστοποιημένης Ιατρικής Θεραπείας στη Δυσκινησία σε Συμμετέχοντες με Προχωρημένη Νόσο Parkinson

A.3.1

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

12-Week study comparing Levodopa-Carbidopa Intestinal Gel / Levodopa Carbidopa Enteral Suspension to Optimized Medical Treatment on dyskinesia in subjects with advanced Parkinson's disease

Μελέτη 12 Εβδομάδων η Οποία Συγκρίνει την Εντερική Γέλη Λεβοντόπα-Καρβιντόπα/Εντερικό Εναιώρημα Καρβιντόπα-Λεβοντόπα και τη Βελτιστοποιημένη Ιατρική Θεραπεία στη Δυσκινησία σε Συμμετέχοντες με Προχωρημένη Νόσο Parkinson

A.3.2

Name or abbreviated title of the trial where available

DYSCOVER Study

A.4.1

Sponsor's protocol code number

M15-535

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	AbbVie House, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628561090
B.5.5	Fax number	+441628461153
B.5.6	E-mail	eu-clinical-trials@abbvie.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	Yes
D.2.1.1.1	Trade name	Duodopa
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Deutschland GmbH & Co. KG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Intestinal gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral 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.3.9.3	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	20
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.3.9.3	Other descriptive name	CARBIDOPA MONOHYDRATE
D.3.9.4	EV Substance Code	SUB21619
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	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

Dyskinesia in advanced Parkinson's disease

E.1.1.1

Medical condition in easily understood language

Advanced 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	LLT
E.1.2	Classification code	10013113
E.1.2	Term	Disease Parkinson's
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this interventional study is to examine the effect of LCIG treatment relative to that of Optimized Medical Treatment (OMT) on dyskinesia as measured by the Unified Dyskinesia Rating Scale (UDysRS) Total Score.

E.2.2

Secondary objectives of the trial

The Secondary objective is to assess the effect of LCIG treatment relative to that of OMT on dyskinesia as measured by PD Diaries, motor symptoms, motor complications, safety, tolerability and health-related outcome measures.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects of at least 30 years old at the time of Visit 3.
2. Subject must have a diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
3. Patients with advanced levodopa-responsive Parkinson's disease and persistent motor fluctuations who have not been controlled with optimized medical treatment. "Optimized medical treatment" is defined as the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected regardless of any additional manipulations of levodopa and/or other antiparkinsonian medication. This will be based on the Investigator's clinical judgment.
4. UDysRS Total score ≥ 30 at Visit 3 based on Central Blinded Rater's score.
5. Subject (or subject's proxy/caregiver) must be able to complete both the Subject Dosing Diary and the PD Diary and must be able to demonstrate the ability to operate, manipulate, and care for the pump and tubing.
6. Subject must demonstrate at least 75% concordance with the Investigator's or qualified designee's assessment of symptoms on the Parkinson's Disease Diary following training at Screening Visit 1 with concordance on at least 1 time interval of "Off," concordance on at least 1 time interval of "ON regardless of dyskinesia" and at least 1 time interval of "ON with dyskinesia" irrespective of whether the dyskinesia are troublesome or not troublesome.
7. Subject is eligible to transfer to commercial treatment of Duodopa after completing the study based on local country requirements.

E.4

Principal exclusion criteria

1. Predominantly di-phasic dyskinesia, as per Investigator discretion.
2. Patients who were treated with LCIG before
3. Patients who have had previous surgery for PD including, but not limited to deep brain stimulation (DBS) or cell transplantation.
4. A Mini-Mental State Examination (MMSE) score of < 24 at Visit 1 or significant cognitive impairment that, in the opinion of the Investigator, could impact the subject's ability to participate in the trial
5. Current primary psychiatric diagnosis of uncontrolled acute psychotic disorder or primary psychiatric diagnoses of bipolar disorder, schizophrenia, obsessive compulsive disorder or currently experiencing a major depressive episode with psychotic features per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, Text Revision (DSM V-TR).
6. Subject experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g., pathological gambling, hypersexuality) at any point during the three months prior to the Screening evaluation as judged by the Investigator.
7. Current diagnosis or history of drug or alcohol abuse (DSM-V-TR criteria) within 12 months prior to screening visit.
8. Participation in a concurrent interventional or observational study.
9. Lack of motivation or insufficient language skills to complete the study questionnaires.
10. Subject's PD diagnosis is unclear or there is a suspicion that the subject has a parkinsonian syndrome such as secondary parkinsonism (e.g., caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), atypical Parkinson Syndrome (e.g., Multiple System Atrophy, Progressive supranuclear Palsy, Diffuse Lewy Body disease) or other neurodegenerative disease that might mimic the symptoms of PD.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit

E.5.2

Secondary end point(s)

Secondary endpoints (with hierarchical analysis)

• ON time without troublesome dyskinesia as measured by the PD Diary
• PDQ-8 Summary Index
• CGI-C
• UPDRS Part II Score
• OFF time as measured by PD Diary
• UPDRS Part III Score

Additional Efficacy Endpoints are:
● UDysRS Historical Score, Objective Score and Parts 1 through 4 Scores
● ON time with troublesome dyskinesia and ON time without dyskinesia as measured by PD Diary
● mAIMS

Additional Health Outcome Endpoints:
● King's PD Pain Scale

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit
2. Baseline, Week 8, Week 12/Early termination visit
3. Week 2, Week 4, Week 8, Week 12/Early termination visit
4. Screening, Baseline, Week 2, Week 4, Week 8, Week 12/Early
termination visit
5. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit
6. Screening, Baseline, Week 2, Week 4, Week 8, Week 12/Early
termination visit
7. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit
8. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit
9. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit
10. Baseline, Week 4, Week 8, Week 12/Early termination visit

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

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

Optimized medical treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

European Union

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

LPLV

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

E.8.9.2

In all countries concerned by the trial days

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 randomized to the LCIG treatment arm will be able to continue the treatment via commercial product. Subjects randomized in the OMT arm will be eligible for commercial LCIG/CLES. All commercial treatment will be provided through the local country's commercial program and local insurance reimbursement.

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

2016-11-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-09-17

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials