Clinical Trials Register

Summary
EudraCT Number:	2004-002407-32
Sponsor's Protocol Code Number:	CSOM230B2208E1
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:	2004-09-16
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

2004-002407-32

A.3

Full title of the trial

Extension to a multicenter, open label study to assess the safety and efficacy of 600 micrograms SOM230, administered subcutaneously, b.i.d. in patients with Cushing's disease

Estensione dello studio multicentrico, in aperto, per valutare la sicurezza e l'efficacia di SOM230, 600 mcg, somministrato sottocute b.i.d. in pazienti con malattia di Cushing.

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

CSOM230B2208E1

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	NOVARTIS FARMA
B.1.3.4	Country	Italy
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NOVARTIS FARMA
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	ORIGGIO
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	+ 39 02 96541
B.5.5	Fax number	+39 02 9659066
B.5.6	E-mail	info.studiclinici@novartis.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	NA
D.3.2	Product code	SOM230B
D.3.4	Pharmaceutical form	Solution for injection
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	PASIREOTIDE
D.3.9.1	CAS number	396091-77-3
D.3.9.2	Current sponsor code	SOM230B
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.3	Concentration number	900
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	No
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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

Treatment of Cushing's disease

Trattamento del morbo di Cushing

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10035109
E.1.2	Term	Pituitary-dependent Cushing's syndrome
E.1.2	System Organ Class	10014698 - Endocrine disorders

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

• To assess the long-term efficacy of SOM230 in patients with Cushing’s disease

- Valutare gli effetti a lungo termine di SOM230 nei pazienti con malattia di Cushing

E.2.2

Secondary objectives of the trial

• To assess the long-term safety and tolerability of SOM230 in patients with Cushing’s disease; • To monitor trough plasma concentrations of SOM230 after chronic dosing; • To investigate gene-expression and protein changes in blood and urine for biomarker development.

ï‚· Valutare la sicurezza e la tollerabilita` a lungo termine di SOM230 nei pazienti con malattia di Cushing.ï‚· Misurare le concentrazioni plasmatiche `€œtrough' di SOM230 dopo somministrazione cronica.ï‚· Valutare l`espressione genica e le modificazioni delle proteine nel sangue e nelle urine per lo studio degli indicatori biologici.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOGENETIC:
Vers:
Date:
Title:
Objectives:

FARMACOGENETICA:
Vers:
Data:
Titolo:
Obiettivi:

ALTRI SOTTOSTUDI:
- Valutazione degli indicatori biologici

E.3

Principal inclusion criteria

• Patients have completed the 15 days of SOM230 treatment in [study CSOM230B2208]. • The patient achieved normalization of 24-hour urinary free cortisol, • If the patient did not achieve normalization of 24 -hour urinary free cortisol, but the investigator believes the patient is getting significant clinical benefits from treatment with SOM230, the patient may be continued on therapy after approval by Novartis. • The patient did not experience any unacceptable adverse events of tolerability issues during the original 15 day treatment. • Karnofsky Performance Status ≥ 60 • Written informed consent to participate in the extension study has been obtained • Female patients of child bearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation must agree to use barrier contraception throughout the course of the extension study, and for one month after the study has ended

Saranno eleggibili allo studio i pazienti che hanno raggiunto la normalizzazione del cortisolo libero urinario delle 24 ore e che soddisfano tutti i criteri d’inclusione. Qualora i valori di cortisolo libero urinario delle 24 ore non fossero normalizzati, ma risultassero migliorati lo sperimentatore dovra` discutere l’eleggibilita` del paziente allo studio con Novartis, e deciderne l’inclusione in base al miglioramento dei valori di cortisolo libero urinario o al miglioramento significativo dei sintomi di ipercortisolismo quali l’ipertensione, dopo 15 giorni di terapia con SOM230.  Pazienti che hanno completato i 15 giorni di trattamento con SOM230 nello studio CSOM230B2208.  Normalizzazione dei livelli di cortisolo libero urinario delle 24 ore.  Se il paziente non raggiunge la normalizzazione dei livelli di cortisolo libero urinario delle 24 ore ma lo sperimentatore ritiene che il paziente abbia ottenuto un beneficio clinico significativo con il trattamento con SOM230, il trattamento con SOM230 potra` essere proseguito dopo l’approvazione di Novartis.  Pazienti che non hanno manifestato eventi aversi inaccettabili o problemi di tollerabilita` dopo 15 giorni di trattamento nel protocollo di studio originale.  Karnofsky Performance Status ≥ 60.  Consenso informato scritto.  Donne potenzialmente in grado di procreare e che non hanno subito un’isterectomia totale e/o ovariectomia, o legatura delle tube, devono adottare un metodo contraccettivo di barriera per tutta la durata dello studio e per un mese dopo il termine dello stesso.

E.4

Principal exclusion criteria

• Patients who have developed poorly controlled diabetes mellitus as indicated by ketoacidosis or HgbA1C > 10 since starting [study CSOM230B2208] • Patients with persistent ALT/AST or alkaline phosphatase levels more than 2.5X ULN, serum creatinine > 2.0 X ULN, serum bilirubin > 2 X ULN • Patients with abnormal coagulation (PT and PTT elevated by 30% above normal limits), WBC <3.0x109/L; Hgb <12.0g/dL for females, Hgb <13.0g/dL for males; PLT<100x109/L

 Pazienti che hanno manifestato un Diabete Mellito scarsamente controllato come indicato da chetoacidosi o HbA1C > 10 dall’inizio dello studio CSOM230B2208.  Livelli costanti di SGOT, SGPT o fosfatasi alcalina piu` di 2,5 volte maggiori dei limiti superiori di normalita` o bilirubina, o creatinina piu` di 2 volte maggiori dei limiti superiori.  Disturbi della coagulazione (PT e PTT elevati, al di sopra del 30% dei limiti della norma), globuli bianchi < 3.0x109/L, emoglobina < 12 g/dL nelle femmine e < 13 g/dL nei maschi, piastrine < 100x109/L.

E.5 End points

E.5.1

Primary end point(s)

- Normalisation of urinary free cortisol levels after 6 months -Normalisation of plasma ACTH and serum cortisol levels

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

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.8.1.7.1

Other trial design description

studio in aperto

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	Yes
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	6
F.4.2	For a multinational trial
F.4.2.1	In the EEA	16
F.4.2.2	In the whole clinical trial	26

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

2004-10-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2004-10-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-08

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