Clinical Trials Register

Summary
EudraCT Number:	2009-016722-13
Sponsor's Protocol Code Number:	CSOM230C2402
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-22
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2009-016722-13

A.3

Full title of the trial

A phase III, multicenter, randomized, parallel-group study to assess the efficacy and safety of double-blind pasireotide LAR 40 mg and pasireotide LAR 60 mg versus open-label octreotide LAR or lanreotide ATG in patients with inadequately controlled acromegaly

A.3.1

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

efficacy and safety of pasireotide LAR 40 and 60 mg versus octreotide LAR
or lanreotide ATG in patients with inadequately controlled acromegaly

A.4.1

Sponsor's protocol code number

CSOM230C2402

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 Pharma Services AG
B.1.3.4	Country	Switzerland
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 Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41643241111
B.5.5	Fax number	+41613248001
B.5.6	E-mail	clinicaltrial.enquiries@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	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/670
D.3 Description of the IMP
D.3.1	Product name	pasireotide
D.3.2	Product code	SOM230C
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular 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	396091-79-5
D.3.9.2	Current sponsor code	SOM230 pamoate
D.3.9.3	Other descriptive name	Cyclo((diaminoethyl-carbamate)HyPro-Phg-(D)Trp-Lys-Tyr(Bzl)-Phe) pamoate
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	pasireotide
D.3.9.1	CAS number	396091-79-5
D.3.9.2	Current sponsor code	SOM230 pamoate
D.3.9.3	Other descriptive name	Cyclo((diaminoethyl-carbamate)HyPro-Phg-(D)Trp-Lys-Tyr(Bzl)-Phe) pamoate
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Sandostatine Long Acting Repeatable 30 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.2	Product code	SMS995
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	octreotide
D.3.9.1	CAS number	79517-01-4
D.3.9.3	Other descriptive name	D-Phenylalanyl-L-hemicystyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-hemiscystyl-L-threonino
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Somatuline Autogel Injectable 120 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen NV
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Information not present in EudraCT
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	lanreotide ATG
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	lanreotide ATG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
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	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

Acromegaly is characterized by chronic hypersecretion of growth hormone (GH), clinical features comprise structural and functional changes occurring in practically all organs. Cardiovascular disease is the main reason for morbidity and increased mortality.

E.1.1.1

Medical condition in easily understood language

acromegaly

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10000599
E.1.2	Term	Acromegaly
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 compare the proportion of patients achieving biochemical control defined as mean GH levels < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continuing the same treatment with octreotide LAR 30 mg or lanreotide ATG 120 mg.

E.2.2

Secondary objectives of the trial

Key Secondary: To compare the effect of pasireotide LAR (40mg and 60
mg seperately) versus continuing the same treatment on the proportion
of patients achieving normalization of sex- and age-adjusted IGF-1 at 24
weeks.
Secondary:
To assess the effect of pasireotide LAR (40 mg and 60 mg separately) vs
continuing the same treatment on the proportion of patients achieving:
•biochemical control defined as mean GH levels < 2.5 μg/L and
normalization of sex- and age-adjusted IGF-1 at 12 weeks,
•GH levels < 2.5 μg/L at 12 and 24 weeks,
•normal, sex- and age-adjusted IGF-1 at 12 weeks,
•GH levels < 1 μg/L and normal, sex- and age-adjusted IGF-1 at 12 and
24 weeks,
•GH levels < 1 μg/L at 12 and 24 weeks,
•a tumor volume reduction > 25% assessed by pituitary MRI at 24
weeks,
see protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Male and female patients ≥ 18 years of age
•Patients with written informed consent prior to any study related activity
•Patients with inadequately controlled acromegaly as defined by
•a mean GH concentration of a 5-point profile over a 2-hour period > 2.5 µg/L
and
•sex- and age adjusted IGF-1 > 1.3 x upper limit of normal (ULN)
•Patients treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to Visit 1 (Screening). The maximum indicated dose for octreotide LAR is 30 mg and for lanreotide ATG is 120 mg
•Patients with diagnosis of pituitary micro- or macro adenoma. Patients can have been previously submitted to surgery

Additional inclusion criteria as per full protocol may apply

E.4

Principal exclusion criteria

1.Patients who have received pasireotide (SOM 230) prior to enrolment
2. Concomitant treatment with Growth Hormone Receptor (GHR)-
antagonist or dopamine agonists unless concomitant treatment was
discontinued 8 weeks prior to visit 1 (screening)(8 weeks wash out
period). Such patients must have been treated with octreotide LAR 30
mg or lanreotide ATG 120 mg monotherapy continuously for a minimum
of 6 months prior to starting combination therapy and they should have
been inadequately controlled on monotherapy.
3. Patients with compression of the optic chiasm causing acute clinically
significant visual field defects
4. Patients who require a surgical intervention for relief of any sign or
symptom associated with tumor compression
5. Patients who have received pituitary irradiation within 10 years prior
to visit 1 (screening).
6. Patients who have undergone major surgery/surgical therapy for any
cause within 4 weeks prior to visit 1 (screening).
7. Patients who are hypothyroid and not adequately treated with a stable
dose of thyroid hormone replacement therapy
Other protocol-defined exclusion criteria may apply

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy endpoint
The proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks

E.5.2

Secondary end point(s)

The endpoint for the key secondary objective is:
• the proportion of patients achieving normalization of sex- and ageadjusted
IGF-1 at 24 weeks.
The secondary end points are:
•the proportion of patients achieving biochemical control defined as
mean GH levels < 2.5 μg/L and normalization of sex- and age-adjusted
IGF-1 at 12 weeks,
•the proportion of patients achieving GH levels < 2.5 μg/L at 12 and 24
weeks,
•the proportion of patients achieving normal IGF-1 (sex- and ageadjusted)
at 12 and 24 weeks,
•the proportion of patients achieving GH levels < 1 μg/L and normal,
sex- and age-adjusted IGF-1 at 12 and 24 weeks,
•the proportion of patients achieving GH levels < 1 μg/L at 12 and 24
weeks,
•the proportion of patients achieving a tumor volume reduction > 25%
assessed by pituitary MRI at24 weeks,•the percent change in tumor volume assessed by pituitary MRI from
baseline to 24 weeks,
•the change from baseline in clinical signs/symptoms of acromegaly
(ring size; headache, fatigue, perspiration, paresthesias and
osteoarthralgia according to a five-point score scale),
•the change from baseline in health related QoL as measured by the
AcroQoL (acromegaly health related QoL),
•the PK levels of pasireotide LAR 40 mg and pasireotide LAR 60 mg.

Additional endpoint as per full protocol may apply

E.5.2.1

Timepoint(s) of evaluation of this end point

Key secondary:
24 weeks
1. 12 weeks
2. 24 weeks
3. 12 and 24 weeks
4. 24 weeks
5. 24 weeks

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of Life (QoL)

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

Information not present in EudraCT

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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)

Yes

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Argentina

Brazil

Israel

Mexico

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

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

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:

119

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

109

F.4.2.2

In the whole clinical trial

219

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)

Patients can continue in the extension study as long as they do not
fulfill any of the study discontinuation criteria or until pasireotide LAR
is commercially available for the treatment of acromegaly (N/A for
Norway and UK) or Dec 2015 (Norway and UK). If pasireotide is not
available, Novartis will have a transition plan to ensure that all trial
patients have access to study medication without delay in the
treatment.

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

2010-08-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-02-28

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