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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00434148
First received: February 9, 2007
Last updated: August 6, 2015
Last verified: August 2015
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
The enrollment number reflects the participants who were randomized and received at least one dose of drug.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 165 participants were randomized, but 1 participant from the 600ug group and 2 participants from the 900ug group were not treated. Participants who completed month 12 and did not enter the extension phase were not counted as discontinuations.

Reporting Groups
  Description
Pasireotide 600 ug At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
Pasireotide 900 ug At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.

Participant Flow:   Overall Study
    Pasireotide 600 ug     Pasireotide 900 ug  
STARTED     82 [1]   80  
Completed Month 12     39     39  
Completed m. 12; Did Not Enter Extension     13     7  
Completed Month 12; Entered Extension     26     32  
COMPLETED     13     7  
NOT COMPLETED     69     73  
Adverse Event                 18                 18  
Lack of Efficacy                 25                 28  
Withdrawal by Subject                 15                 15  
Protocol Violation                 4                 0  
Administrative problems                 6                 10  
Lost to Follow-up                 0                 1  
Condition no longer requires study drug                 1                 0  
Abnormal test procedure result                 0                 1  
[1] "Started" indicates Full Analysis Set. Patients randomized and treated.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Pasireotide 600 ug At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
Pasireotide 900 ug At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Total Total of all reporting groups

Baseline Measures
    Pasireotide 600 ug     Pasireotide 900 ug     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
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1.  Primary:   Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group   [ Time Frame: 6 months ]

2.  Secondary:   Change From Baseline in mUFC   [ Time Frame: baseline, 3 months, 12 months ]

3.  Secondary:   Time to First UFC Response   [ Time Frame: 12 months ]

4.  Secondary:   Percent Change From Baseline in Serum Cortisol   [ Time Frame: baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months ]

5.  Secondary:   Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)   [ Time Frame: baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months ]

6.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

7.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60 ]

8.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

9.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

10.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score   [ Time Frame: baseline, month 3, month 6, month 12, month 18, month 24 ]

11.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

12.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD)   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

13.  Secondary:   Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition   [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ]

14.  Secondary:   Change From Baseline in Tumor Volume   [ Time Frame: baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months ]

15.  Secondary:   Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score   [ Time Frame: baseline, 3 months, 6 months, 12 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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:
unchecked 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.
unchecked 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.


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:

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: August 6, 2015
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