Clinical Trials Register

Summary
EudraCT Number:	2020-003372-41
Sponsor's Protocol Code Number:	TP-0007
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-06-15
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

2020-003372-41

A.3

Full title of the trial

Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa via the DopaFuse® Delivery System in Parkinson’s Disease Patients

Valutazione della farmacocinetica, della sicurezza, della tollerabilità e dell'efficacia del trattamento orale continuato con levodopa mediante il sistema di somministrazione DopaFuse® in pazienti affetti da malattia di Parkinson

A.3.1

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

Investigating the DopaFuse® Delivery System in Parkinson's Disease Patients. Assessing safety, effectiveness, how well it is tolerated, and how the drug is processed by the body.

Studio del sistema di rilascio DopaFuse® nei pazienti con malattia di Parkinson. Valutarne la sicurezza, l'efficacia, la tollerabilità, e come il farmaco viene elaborato dall'organismo.

A.3.2

Name or abbreviated title of the trial where available

Study of Continuous Oral Levodopa: SCOL

Studio sul trattamento orale continuato con levodopa: SCOL

A.4.1

Sponsor's protocol code number

TP-0007

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	SynAgile Corporation
B.1.3.4	Country	United States
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	Synagile Corporation
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	TFS Trial Form Support International AB
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	PO Box 165
B.5.3.2	Town/ city	Lund
B.5.3.3	Post code	SE-221 00
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046462801800
B.5.5	Fax number	0046462801801
B.5.6	E-mail	regulatory@tfscro.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	DopaFuse Delivery System
D.3.2	Product code	[N04BA]
D.3.4	Pharmaceutical form	Oral paste
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral 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	NA
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/h milligram(s)/hour
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	68
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	28860-95-9
D.3.9.2	Current sponsor code	NA
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/h milligram(s)/hour
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	17
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Motor symptoms in Parkinson's Disease

Sintomi motori del morbo di Parkinson

E.1.1.1

Medical condition in easily understood language

motor (movement) symptoms of Parkinson's disease

Sintomi motori (movimento) della malattia di Parkinson

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	20.0
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

The purpose of this study is to evaluate whether the DopaFuse System can reduce the fluctuation of plasma levodopa levels as compared to participants' standard intermittent doses of oral LD/CD tablets
(background treatment).

Lo scopo di questo studio è valutare se il sistema DopaFuse può ridurre la fluttuazione dei livelli plasmatici di levodopa rispetto a dosi intermittenti standard dei partecipanti di compresse orali LD / CD
(trattamento di fondo).

E.2.2

Secondary objectives of the trial

The secondary objective is to assess whether the DopaFuse system is safe, well tolerated, and can relieve motor symptoms

L'obiettivo secondario è valutare se il sistema DopaFuse è sicuro, ben tollerato e può alleviare i sintomi motori

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosis of Parkinson's Disease consistent with UK Brain Bank Criteria
2. Age at least 30 years old at time of consent
3. Male and Female participants (Women of child-bearing potential (WOCB) are eligible for participation if they are not pregnant or breastfeeding and agree to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 30 days after the last dose of study treatment)
4. Suitable for oral retainer wear
5. A good response to Levodopa, as assessed by the Investigator
6. At least 2 hours of wearing OFF time per day, as reported by the
participant
7. Predictable early morning OFF periods, in the judgement of the participant and the Investigator
8. Taking 400-1,200 mg of LD/CD per day in at least 4 doses, with stable dosing for the last 28 days prior to screening.
9. A modified Hoehn and Yahr of ¿ 3 in the ON state at screening
10. A stable regimen of anti-PD medications for the last 28 days prior to Screening
11. A Mini-Mental State Examination (MMSE) Score =26
12. Capable of giving signed informed consent Approved for entry into the study by the Enrollment

1. Diagnosi di malattia di Parkinson secondo i criteri della UK Brain Bank
2. Età pari ad almeno 30 anni al momento del consenso
3. Partecipanti di sesso maschile e femminile (le donne potenzialmente fertili [Women of Child-Bearing Potential, WOCB] possono partecipare se non sono in gravidanza o in allattamento e accettano di seguire le linee guida sulla contraccezione di cui all'Appendice 3 durante il periodo di trattamento e per almeno 30 giorni dopo l'ultima dose del trattamento in studio)
4. Pazienti adatti ad indossare un apparecchio di contenzione orale
5. Buona risposta alla levodopa secondo la valutazione dello sperimentatore
6. Almeno 2 ore al giorno di tempo di wearing OFF (effetto di fine dose), in base a quanto riportato dal partecipante
7. Prevedibili periodi di OFF di prima mattina, a giudizio del partecipante e dello sperimentatore
8. Assunzione di 400-1.200 mg di LD/CD al giorno in almeno 4 dosi, con dosaggio stabile negli ultimi 28 giorni prima dello screening
9. Punteggio modificato sulla scala Hoehn e Yahr ¿3 nello stato ON allo screening
10. Regime stabile di farmaci anti-PD negli ultimi 28 giorni prima dello screening
11. Punteggio MMSE (Mini-Mental State Examination, Mini esame dello stato mentale) =26
12. Capacità di fornire il consenso informato firmato

E.4

Principal exclusion criteria

1. Atypical or secondary Parkinson's Disease
2. Severe Dyskinesia that might interfere with study performance in the judgement of Investigator
3. Clinically significant dysphagia or sialorrhea that might interfere with administration of study intervention in the judgement of the Investigator
4. Use of extended release levodopa within 28 days prior to screening
5. Any clinically significant medical, surgical, or psychiatric condition; laboratory value or ECG result which, in the opinion of the Investigator, makes the participant unsuitable for study entry or potentially unable to complete all aspects of the study.
6. Presence of clinically significant orthostatic hypotension at screening, in the opinion of Investigator or the EAC
7. Suicidal ideation within 1 year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
8. History of psychosis or hallucinations in the past six months
9. Any malignancy in the past 5 years (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated.)
10. Current or previous diagnosis of malignant melanoma or the presence of any suspicious skin lesion based on physical exam findings
11. Unable to give blood required for the study
12. History of allergic reaction to plastics
13. LD infusion therapy (i.e. Duodopa); current or previous continuous apomorphine infusion treatment.
14. Participation in any other clinical trial <30 days prior to screening visit.
15. Presence of two third molars ("wisdom teeth") on the upper dentition
16. Participants who, for any reason, are judged by the Investigator or the EAC to be inappropriate for this study, including participants who are unable to communicate or cooperate with the Investigator or who have/had a clinically significant illness or abnormal physical examination that may compromise safety of the participant during the trial or affect ability of the participant to adhere to study procedures.
17. Participants taking non-selective monoamine oxidase (MAO) inhibitors
18. Participants with known hypersensitivity to the active ingredients (levodopa, carbidopa) or excipients (Benzoic Acid, Disodium Edetate, Medium Chain Triglycerides, Poloxamer 188) of the drug paste
19. Participants with narrow-angle glaucoma

1. Malattia di Parkinson atipica o secondaria
2. Discinesia grave che, secondo il giudizio dello sperimentatore, potrebbe interferire con le prestazioni dello studio
3. Disfagia o scialorrea clinicamente significativa che, secondo il giudizio dello sperimentatore, potrebbe interferire con la somministrazione del trattamento in studio
4. Uso di levodopa a rilascio prolungato entro 28 giorni prima dello screening
5. Qualsiasi condizione medica, chirurgica o psichiatrica clinicamente significativa; valore di laboratorio o risultato ECG che, a parere dello sperimentatore, rende il partecipante non idoneo all'ingresso nello studio o potenzialmente incapace di completare tutti gli aspetti dello studio
6. Presenza di ipotensione ortostatica clinicamente significativa allo screening, secondo il parere dello sperimentatore o dell'EAC
7. Ideazione suicidaria entro un anno prima della Visita di screening, come evidenziato dalla risposta “sì” alle domande 4 o 5 della sezione sull’ideazione suicidaria della scala della Columbia University sulla valutazione della gravità del rischio di suicidio (Columbia Suicide Severity Rating Scale, C-SSRS) o da un tentativo di suicidio negli ultimi 5 anni
8. Storia di psicosi o allucinazioni negli ultimi sei mesi
9. Qualsiasi neoplasia maligna negli ultimi 5 anni (con l'esclusione del carcinoma cutaneo basocellulare o del carcinoma della cervice in situ trattati efficacemente)
10. Diagnosi attuale o precedente di melanoma maligno o presenza di qualsiasi lesione cutanea sospetta sulla base dei risultati dell'esame obiettivo
11. Incapacità di sottoporsi ai prelievi di sangue richiesti per lo studio
12. Anamnesi di reazione allergica alla plastica
13. Terapia infusionale a base di LD (ad es. Duodopa); trattamento infusionale attuale o precedente a base di apomorfina
14. Partecipazione a un altro studio clinico <30 giorni prima della visita di screening
15. Presenza di due terzi molari (“denti del giudizio”) sulla dentatura superiore
16. Partecipanti che, per qualsiasi motivo, sono giudicati dallo sperimentatore o dall'EAC inappropriati per questo studio, compresi i partecipanti che non sono in grado di comunicare o collaborare con lo sperimentatore o che hanno/hanno avuto una malattia clinicamente significativa o un risultato anomalo all'esame obiettivo che potrebbe comprometterne la sicurezza durante lo studio o la capacità di aderire alle procedure dello studio
17. Partecipanti che assumono inibitori non selettivi della monoamino ossidasi (MAO)
18. Partecipanti con ipersensibilità nota ai principi attivi (levodopa, carbidopa) o agli eccipienti (acido benzoico, edetato disodico, trigliceridi a catena media, poloxamero 188) della pasta contenente il farmaco
19. Partecipanti con glaucoma ad angolo stretto

E.5 End points

E.5.1

Primary end point(s)

PHARMACOKINETICS:
- Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage), comparing Day 2 to Day 1 in steady state (4-12 hours). Fluctuation index will also be calculated by the hour.
SAFETY AND TOLERABILITY:
- TEAEs
- SAEs
- TEAEs leading to discontinuation
- Percent of participants that complete study
EFFICACY:
- Difference in OFF time between Days 1 and 15, based on in-person investigator ratings

Farmacocinetica:
Variabilità della concentrazione plasmatica di levodopa, valutata mediante l'indice di fluttuazione della levodopa (Cmax-Cmin)/Cmedia), confrontando il Giorno 2 con il Giorno 1 allo stato stazionario (4-12 ore). L'indice di fluttuazione sarà calcolato anche in base all'ora
Sicurezza e tollerabilità
• TEAE
• SAE
• TEAE che causano l'interruzione del trattamento
• Percentuale di partecipanti che completano lo studio
Efficacia
• Differenza nel tempo OFF tra i Giorni 1 e 15, in base alle valutazioni condotte di persona dallo sperimentatore

E.5.1.1

Timepoint(s) of evaluation of this end point

PK: Day 1 to 2
Efficacy: Day 1 to Day 15
Safety: Day 1 to Day 29

PK: dal giorno 1 al giorno 2
Efficacia: dal giorno 1 al giorno 15
Sicurezza: dal giorno 1 al giorno 29

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

E.8.1.1

Randomised

E.8.1.2

Open

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

Last visit of the last participant in the study, OR Last scheduled procedure shown in the Schedule of Activities for the last participant in the trial globally.

Ultima visita dell'ultimo partecipante allo studio, OPPURE Ultima procedura programmata mostrata nel Programma delle attività per l'ultimo partecipante allo studio a livello globale.

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)

none

nessuno

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

2021-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-25

P. End of Trial
P.	End of Trial Status	Completed

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