Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) (EXIST-2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00790400
First received: November 10, 2008
Last updated: January 14, 2014
Last verified: January 2014
Results First Received: May 23, 2012  
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
Conditions: Tuberous Sclerosis Complex (TSC)
Lymphangioleiomyomatosis (LAM)
Interventions: Drug: Everolimus (RAD001)
Drug: Placebo

  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
No text entered.

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
Everolimus Study drug was given by continuous oral daily dosing of two 5 mg tablets.
Placebo Placebo was given by continuous oral daily dosing of two 5 mg tablets.

Participant Flow:   Overall Study
    Everolimus     Placebo  
STARTED     79     39  
COMPLETED     7 [1]   13  
NOT COMPLETED     72     26  
Ongoing in Double-blind                 72                 26  
[1] Completed means discontinued the double-blind treatment period



  Baseline Characteristics


  Outcome Measures
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1.  Primary:   Angiomyolipoma Response Rate as Per Central Radiology Review (Double-blind Period)   [ Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or analysis cut-off date (30-June-2011). ]
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Measure Type Primary
Measure Title Angiomyolipoma Response Rate as Per Central Radiology Review (Double-blind Period)
Measure Description

Angiomyolipoma response defined as the combination of the following criteria:

reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later)• No new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified.• There were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2

Time Frame From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or analysis cut-off date (30-June-2011).  
Safety Issue No  

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.
The Full Analysis Set (FAS) is defined according to the Intention-to-Treat principle and consists of all randomized patients. Patients were to be analyzed according to the treatment that they were assigned to at randomization.

Reporting Groups
  Description
Everolimus Study drug was given by continuous oral daily dosing of two 5 mg tablets.
Placebo Placebo was given by continuous oral daily dosing of two 5 mg tablets.

Measured Values
    Everolimus     Placebo  
Number of Participants Analyzed  
[units: participants]
  79     39  
Angiomyolipoma Response Rate as Per Central Radiology Review (Double-blind Period)  
[units: Percentage¬†of¬†Participants]
Number ( 95% Confidence Interval )
  41.8  
  ( 30.8 to 53.4 )  
  0  
  ( 0.0 to 9.0 )  

No statistical analysis provided for Angiomyolipoma Response Rate as Per Central Radiology Review (Double-blind Period)



2.  Secondary:   Time to Angiomyolipoma Progression as Per Central Radiology Review (Double-blind Period)   [ Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or analysis cut-off date (30-June-2011). ]

3.  Secondary:   Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)   [ Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or analysis cut-off date (30-June-2011). ]

4.  Secondary:   Percentage of Participants With Renal Impairment   [ Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or analysis cut-off date (30-June-2011). ]

5.  Secondary:   Change From Baseline in Plasma Angiogenic Molecules   [ Time Frame: Baseline, 12 Months ]
Results not yet posted.   Anticipated Posting Date:   12/2014   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  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.


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: Novartis Pharmaceuticals
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


Publications:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00790400     History of Changes
Other Study ID Numbers: CRAD001M2302, 2008-002113-48
Study First Received: November 10, 2008
Results First Received: May 23, 2012
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Japan: Ministry of Health, Labour and Welfare, Pharmaceutical amd Medical Safety Bureau
Netherlands: Medical Ethics Review Committee (METC)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Federal Service on Surveillance in Healthcare and Social Development of Russian Federation
Spain: Ministerio de Sanidad y Politica Social
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Japan: Ministry of Health, Labour and Welfare, Pharmaceutical and Medical Safety Bureau