Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT00434148

First received: February 9, 2007

Last updated: February 5, 2013

Last verified: February 2013

History of Changes

Results First Received: January 3, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Cushing's Disease
Intervention:	Drug: Pasireotide

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
165 patients were randomized, however 1 patient from the 600 microgram group and 2 patients from the 900 microgram group were not treated.

Reporting Groups

	Description
600ug b.i.d	All patients received a double blind dose of 600 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment if their Month 3 mUFC was a ≤2 X ULN and b) below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblinded and were required to increase their dose to 900 µg b.i.d, given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 900 µg b.i.d dose were to be discontinued from the study.
900ug b.i.d	All patients received a double blind dose of 900 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment) if their Month 3 mUFC was a) ≤ 2 x ULN and b)below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblended and were offered to increase their dose to 1200 µg b.i.d., given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 1200 µg b.i.d dose were to be discontinued from the study. [China only: Patients in the 900 µg b.i.d dose group were not offered to have their dose increased to 1200 µg b.i.d but had to be discontinued.

Description

600ug b.i.d

All patients received a double blind dose of 600 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment if their Month 3 mUFC was a ≤2 X ULN and b) below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblinded and were required to increase their dose to 900 µg b.i.d, given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 900 µg b.i.d dose were to be discontinued from the study.

900ug b.i.d

All patients received a double blind dose of 900 µg subcutaneously ( s.c.) two times a day ( b.i.d) Pasireotide. Patients continued at this dose until Month 6 (double-blind treatment) if their Month 3 mUFC was a) ≤ 2 x ULN and b)below or equal to their baseline mUFC. Patients not meeting these mUFC criteria at Month 3 were unblended and were offered to increase their dose to 1200 µg b.i.d., given on an open-label basis. These patients were classified as non-responders for the Month 6 Primary analysis. Patients who did not escalate to the 1200 µg b.i.d dose were to be discontinued from the study. [China only: Patients in the 900 µg b.i.d dose group were not offered to have their dose increased to 1200 µg b.i.d but had to be discontinued.

Participant Flow: Overall Study

	600ug b.i.d	900ug b.i.d
STARTED	82 ^[1]	80
Ongoing in Extension Phase	19	25
COMPLETED	33	32
NOT COMPLETED	49	48
Adverse Event	13	15
Lack of Efficacy	19	22
Withdrawal by Subject	13	11
Protocol Violation	4	0

[1]	"Started" indicates Full Analysis Set. Patients randomized and treated.

Baseline Characteristics

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Reporting Groups

	Description
600ug b.i.d	No text entered.
900ug b.i.d	No text entered.
Total	Total of all reporting groups

Baseline Measures

	600ug b.i.d	900ug b.i.d	Total
Number of Participants [units: participants]	82	80	162
Age [units: years] Mean ± Standard Deviation	40.5 ± 12.97	39.9 ± 10.77	40.2 ± 11.90
Gender [units: participants]
Female	62	64	126
Male	20	16	36

Outcome Measures

1. Primary:

Proportion of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group [ Time Frame: 6 months ]

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2. Secondary:

Reduction of UFC at Months 3 and 12 [ Time Frame: 3 and 12 months ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

3. Secondary:

Time to First Response [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

4. Secondary:

Assessment of Plasma ACTH and Serum Cortisol Level [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

5. Secondary:

Assessment of Clinical Signs and Symptoms [ Time Frame: Month 1, 2, 3, 4, 5, 6, 12 and every 3 months to study end. ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:

Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300

No publications provided by Novartis

Publications automatically indexed to this study:

Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Dipl-Biol, Mills D, Salgado LR, Biller BM; Pasireotide B2305 Study Group. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med. 2012 Mar 8;366(10):914-24.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00434148 History of Changes
Other Study ID Numbers:	CSOM230B2305, 2006-004111-22
Study First Received:	February 9, 2007
Results First Received:	January 3, 2013
Last Updated:	February 5, 2013
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Brazil: National Health Surveillance Agency Canada: Health Canada China: Ministry of Health Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: German Institute of Medical Documentation and Information Greece: National Organization of Medicines Italy: The Italian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Spain: Ministry of Health and Consumption Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

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