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Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease

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ClinicalTrials.gov Identifier: NCT01374906
Recruitment Status : Completed
First Posted : June 16, 2011
Results First Posted : April 11, 2018
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cushing's Disease
Interventions: Drug: pasireotide LAR
Drug: SOM230 LAR 30 mg
Drug: SOM230 LAR 10 mg

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
At least 148 patients (Pts.) were planned & 150 were randomized & analyzed. Pts. were all treated with either pasireotide long-acting 10 mg or pasireotide long-acting 30 mg. 81 Pts. completed the Core phase & entered the Extension phase with 39 completing the Extension phase.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
10 mg Pasireotide LAR Dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
30 mg Pasireotide LAR Dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.

Participant Flow:   Overall Study
    10 mg Pasireotide LAR Dose   30 mg Pasireotide LAR Dose
STARTED   74   76 
DC Dur Core Phs at/Prior to Data Cutoff   24   22 
Completed Core Phase   50   54 
Completed Core/Did Not Enter Ext. Phase   10   13 
Completed Core Phase/Entered Ext. Phase   40   41 
DC Dur Ext Phs at/Prior to Data Cutoff   16   26 
Completed Extension Phase   24   15 
COMPLETED   34   28 
NOT COMPLETED   40   48 
Abnormal laboratory value(s)                0                3 
Administrative problems                2                2 
Adverse Event                10                11 
Death                0                2 
Protocol Violation                2                2 
Withdrawal by Subject                15                9 
Unsatisfactory therapeutic effect                11                19 



  Baseline Characteristics

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.
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
10 mg Pasireotide LAR Dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
30 mg Pasireotide LAR Dose Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Total Total of all reporting groups

Baseline Measures
   10 mg Pasireotide LAR Dose   30 mg Pasireotide LAR Dose   Total 
Overall Participants Analyzed 
[Units: Participants]
 74   76   150 
Age 
[Units: Years]
Mean (Standard Deviation)
 38.3  (12.52)   38.6  (12.99)   38.5  (12.72) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      58  78.4%      60  78.9%      118  78.7% 
Male      16  21.6%      16  21.1%      32  21.3% 
Race/Ethnicity, Customized 
[Units: Participants]
     
Caucasian   39   44   83 
Asian   27   24   51 
Black   2   0   2 
Other   6   8   14 


  Outcome Measures

1.  Primary:   Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration   [ Time Frame: Month 7 ]

2.  Secondary:   Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4   [ Time Frame: Month 7 ]

3.  Secondary:   Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline   [ Time Frame: baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36) ]

4.  Secondary:   Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline   [ Time Frame: M7, M12, M24, M36 ]

5.  Secondary:   Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN   [ Time Frame: M7, M12, M24, M36 ]

6.  Secondary:   Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC   [ Time Frame: M7, M12, M24, M36 ]

7.  Secondary:   Percentage of Patients Who Are Controlled Responders (mUFC ≤ 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12.   [ Time Frame: Month 7, Month 12 ]

8.  Secondary:   Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3   [ Time Frame: Month 7, Month12 ]

9.  Secondary:   Time to First Achievement of Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline   [ Time Frame: Momth 7, Month 12 ]

10.  Secondary:   Duration of Controlled or Partially Controlled Response   [ Time Frame: Month 6, 12, 18 ]

11.  Secondary:   Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time   [ Time Frame: Months 7, 12, 24 & 36 ]

12.  Secondary:   Percentage Change From Baseline on Serum Cortisol Over Time   [ Time Frame: Months 7, 12, 24 & 36 ]

13.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure   [ Time Frame: Month 7 ]

14.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)   [ Time Frame: Month 7 ]

15.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Weight   [ Time Frame: Month 7 ]

16.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region   [ Time Frame: Month 7 ]

17.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference   [ Time Frame: Month 7 ]

18.  Secondary:   Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides   [ Time Frame: Month 7 ]

19.  Secondary:   Percentage Change From Baseline in Clinical Signs Over Time   [ Time Frame: Month 7 ]

20.  Secondary:   Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs   [ Time Frame: Month 7 ]

21.  Secondary:   Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4.   [ Time Frame: Month 7 ]

22.  Secondary:   Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline   [ Time Frame: Months 7, 12, 24 & 36 ]

23.  Secondary:   Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline   [ Time Frame: every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015) ]

24.  Secondary:   Duration of at Least 50% Reduction in mUFC From Baseline   [ Time Frame: Months 6, 12 & 18 ]

25.  Secondary:   Pharmacokinetic (PK) Parameter: Ctrough   [ Time Frame: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337 ]

26.  Secondary:   Pharmacokinetic (PK) Parameter: Cmax   [ Time Frame: Days 22, 106, 190 ]

27.  Secondary:   Actual Change in Standardized Score of Cushing’s Disease HRQoL (CushingQOL) Score From Baseline   [ Time Frame: Months 7, 12, 24 & 36 ]

28.  Secondary:   Actual Change in SF-12v2 Score From Baseline - Mental Component Summary   [ Time Frame: Months 7, 12 & 24 ]

29.  Secondary:   Actual Change in SF-12v2 Score From Baseline - Physical Component Summary   [ Time Frame: Months 7, 12 & 24 ]


  Serious Adverse Events


  Other Adverse Events


  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
All analyses in this study were descriptive in nature. No comparisons were made between the two arms, and no p-values are reported. For the primary and key-secondary, success was based on estimating the response rate (and 95% CI) in each arm.


  More Information

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
e-mail: novartis.email@novartis.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01374906     History of Changes
Other Study ID Numbers: CSOM230G2304
2009-011128-70 ( EudraCT Number )
First Submitted: June 14, 2011
First Posted: June 16, 2011
Results First Submitted: December 11, 2017
Results First Posted: April 11, 2018
Last Update Posted: April 11, 2018