Clinical Trials Register

Summary
EudraCT Number:	2014-004865-26
Sponsor's Protocol Code Number:	M12-927
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-05-29
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-004865-26

A.3

Full title of the trial

An Open-label, Randomized 26-Week Study Comparing Levodopa-Carbidopa INteStInal Gel (LCIG) Therapy to Optimized Medical Treatment (OMT) on Non-Motor Symptoms (NMS) in Subjects with Advanced Parkinson's Disease – INSIGHTS Study

“Sperimentazione in Aperto, Randomizzata, della durata di 26 Settimane, per Valutare gli Effetti di Levodopa-Carbidopa Gel Intestinale (LCIG) Rispetto al Trattamento Medico Ottimizzato (Optimized Medical Treatment, OMT) sui Sintomi Non-Motori (NMS) in Soggetti con Malattia di Parkinson in Fase Avanzata – Studio INSIGHTS”

A.3.1

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

26-Week Study Comparing Levodopa-Carbidopa Intestinal Gel to Optimized Medical Treatment on Non-Motor Symptoms in Subjects with Advanced Parkinson's Disease

“Sperimentazione della durata di 26 Settimane, per Valutare gli Effetti di Levodopa-Carbidopa Gel Intestinale rispetto al Trattamento Medico Ottimizzato sui Sintomi Non-Motori in Soggetti con Malattia di Parkinson in Fase Avanzata”

A.3.2

Name or abbreviated title of the trial where available

INSIGHTS Study

Studio INSIGHTS

A.4.1

Sponsor's protocol code number

M12-927

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	Abbott House, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628773355
B.5.5	Fax number	+441628644330
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/01/035
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

Non-motor symptoms in advanced Parkinson's disease

Sintomi non motori nella malattia di Parkinson in fase avanzata

E.1.1.1

Medical condition in easily understood language

Advanced Parkinson's disease

Malattia di Parkinson in fase avanzata

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	18.0
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 study is to examine the effect of LCIG relative to that of OMT on non motor symptoms associated with advanced Parkinson's disease.

L’obiettivo primario di questa sperimentazione è valutare l’effetto del trattamento con LCIG rispetto al trattamento medico ottimizzato (OMT) sui sintomi non motori che si associano alla Malattia di Parkinson (MP) in fase avanzata.

E.2.2

Secondary objectives of the trial

To assess the effect of LCIG relative to that of OMT on the motor symptoms/motor complications, safety, tolerability and health-related outcome measures.

Valutare gli effetti del trattamento con LCIG rispetto a OMT sui parametri relativi a: sintomi motori/complicanze motorie, sicurezza, tollerabilità ed esiti correlati alla salute.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject must have a minimum PDSS-2 total score of 20 at Baseline assessment.
2. Subject must have a diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria. See Appendix C for UKPDS.
3. Subject demonstrates persistent motor fluctuations in spite of individually optimized treatment.
4. The subject's Parkinson's disease is levodopa-responsive.
5. Subject has had optimal treatment with available anti-PD medication and their motor symptoms are judged inadequately controlled on this optimized treatment. Optimized 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.
6. Subject and/or if applicable, their care-partner must be able to complete the Subject Dosing Diary and must be able to demonstrate the ability to operate, manipulate and care for the infusion pump and tubing.

1) Soggetto con un punteggio totale PDSS-2 pari ad almeno 20 alla valutazione eseguita al Baseline;
2) Il soggetto deve avere una diagnosi di malattia di Parkinson idiopatica secondo i criteri Brain Bank UKPDS (United Kingdom Parkinson’s Diseases Society).Vedere Appendice C per UKPDS;
3) Soggetto che dimostra fluttuazioni motorie persistenti nonostante l’ottimizzazione del trattamento personalizzato;
4) Soggetto con malattia di Parkinson responsivo alla levodopa;
5) Soggetto i cui sintomi motori non sono risultati controllati in maniera adeguata dal trattamento ottimizzato con i farmaci antiparkinson disponibili. Per trattamento ottimizzato si intende l’effetto terapeutico massimo ottenuto con le terapie farmacologiche antiparkinson, quando non sono attesi ulteriori miglioramenti indipendentemente da qualsiasi ulteriore aggiustamento della levodopa e/o di altri farmaci antiparkinson. Tale valutazione si baserà sul giudizio clinico dello sperimentatore; 6) Soggetto e/o, se applicabile, caregiver in grado di compilare il Diario di Somministrazione del Soggetto e di dimostrare la propria capacità di operare, maneggiare ed avere cura della pompa per infusione e dei sondini.

E.4

Principal exclusion criteria

1. 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), parkinson-plus syndrome (e.g., Multiple System Atrophy, Progressive supranuclear Palsy, Diffuse Lewy Body disease) or other neurodegenerative disease that might mimic the symptoms of PD.
2. Subject has undergone neurosurgery for the treatment of Parkinson's disease.
3. Subject has any neurological deficit that might interfere with the study assessments (e.g., hemiparesis).
4. Known hypersensitivity to levodopa, carbidopa or radiopaque material.
5. Subject has contraindications to levodopa, (e.g., narrow angle glaucoma, malignant melanoma).
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 Principal Investigator.
7.Subject has undergone apomorphine continuous infusion for the treatment of Parkinson's disease

1) Soggetti la cui diagnosi di Malattia di Parkinson non è chiara o per cui si sospetti una sindrome parkinsoniana quali parkinsonismo secondario (es., indotto da farmaci, tossine, agenti infettivi, vasculopatia, trauma, neoplasie cerebrali), sindrome Parkinson Plus (es, Atrofia Sistemica Multipla, Paralisi Sopranucleare Progressiva, Malattia a Corpi di Lewy Diffusi) o altre patologie neurodegenerative che mimano i sintomi di Parkinson;
2) Soggetti sottoposti a intervento neurochirurgico per il trattamento della malattia di Parkinson;
3) Soggetti con qualsiasi deficit neurologico in che interferisca con le valutazioni previste per la sperimentazione (es., emiparesi);
4) Nota ipersensibilità a levodopa, carbidopa o a materiale radiopaco
5) Soggetti che presentano controindicazioni alla levodopa (es., glaucoma ad angolo stretto, melanoma maligno)
6) Soggetti che presentano colpi di sonno oppure comportamento impulsivo (es., gioco d’azzardo patologico, ipersessualità) considerati clinicamente significativi dallo Sperimentatore Principale in qualsiasi momento nei tre mesi precedenti le valutazioni dello Screening;
7) Soggetti che hanno ricevuto infusione continua di apomorfina per il trattamento della malattia di Parkinson

E.5 End points

E.5.1

Primary end point(s)

Non-Motor Symptoms Scale (NMSS) Total Score and the Modified Parkinson's Disease Sleep Scale (PDSS-2) Total Score.

Punteggio totale della scala NMSS (Non-Motor Symptoms Scale) e punteggio totale della scala modificata PDSS-2 (Modified Parkinson’s Disease Sleep Scale).

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, Week 6, Week 12, Week 26

Basale, Settimana 6, Settimana 12, Settimana 26

E.5.2

Secondary end point(s)

Motor symptoms/motor complications will be measured by •Unified Parkinson's Disease Rating Scale (UPDRS) Parts III and IV

Safety and tolerability will be assessed by:
• Adverse event monitoring
• Neurological exams
• Clinical laboratory evaluations
• Electrocardiogram
• Vital signs and weight
• Columbia Suicide Severity Rating Scale (C-SSRS)
• Minnesota Impulsive Disorders Interview (MIDI)
● Sleep Attacks Questionnaire (SAQ)

Health Related Outcomes will be measured by:
• Parkinson's Disease Questionaire-8 (PDQ-8)
• Clinical Global Impression of Change (CGI-C)
• UPDRS Parts I and II
• Patient Global Impression of Change (PGIC)
• Montreal Cognitive Assessment Test (MOCA)
• PD Anxiety Index (PAS)
• Geriatric Depression Scale (GDS-15)
• King PD Pain Scale

Sintomi motori/complicanze motorie saranno valutati mediante:
•Scala UPDRS (Unified Parkinson’s Disease Rating Scale), Parti III e IV
Sicurezza e tollerabilità saranno valutate mediante:
•Monitoraggio degli eventi avversi
•Esami neurologici
•Analisi cliniche di laboratorio
•Elettrocardiogramma
•Segni vitali e peso
•Scala C-SSRS (Columbia Suicide Severity Rating Scale)
•MIDI (Minnesota Impulsive Disorders Interview)
•SAQ (Sleep Attacks Questionnaire)
Gli esiti correlati alla salute saranno misurati in base ai seguenti parametri:
•Questionario PDQ-8 (Parkinson’s Disease Questionnaire-8)
•Scala CGI-C (Clinical Global Impression of Change)
•Scala UPDRS, Parti I e II
•Scala PGIC (Patient Global Impression of Change)
•Scala MOCA (Montreal Cognitive Assessment Test)
•Scala PAS (Parkinson Anxiety Scale)
•Scala GDS-15 (Geriatric Depression Scale)
•Scala King’s relativa al dolore associato alla Malattia di Parkinson

E.5.2.1

Timepoint(s) of evaluation of this end point

UPDRS Parts III and IV:Screening, Baseline, Week6, Week 12, Week 26
Safety and Tolerability: every visit
HEOR: Baseline, Week 6, Week 12, Week 26

Scala UPDRS (Unified Parkinson’s Disease Rating Scale), Parts III and IV: Screening, Basale, Settimana 6, Settimana 12, Settimana 26
Sicurezza e Tollerabilità: ogni visita
HEOR (Health Economics and Outcomes Research): Basale, Settimana 6, Settimana 12, Settimana 26

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

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

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

Australia

Canada

European Union

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. All commercial treatment will be provided through the local country's commercial program and local insurance reimbursement.

I soggetti randomizzati nel braccio LCIG avranno la possibilità di continuare il trattamento con il farmaco commerciale. I soggetti randomizzati nel braccio OMT saranno eliggibili a passare al trattamento con il farmaco commerciale LCIG. Tutti i trattamenti con farmaco commerciale saranno rimborsati seguendo le normali procedure locali.

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

2015-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-21

P. End of Trial
P.	End of Trial Status	Ongoing

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