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)

• 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). ] [ Designated as safety issue: No ]
  Time to angiomyolipoma progression (TTAP) is defined as time from date of randomization to date of first documented angiomyolipoma progression. Angiomyolipoma progression was defined as one or more of the following: • Increase from nadir of ≥ 25% in angiomyolipoma volume to value greater than baseline • The appearance of a new angiomyolipoma ≥ 1.0 cm in longest diameter •An increase from nadir of 20% or more in the volume of either kidney to a value greater than baseline •Angiomyolipoma-related bleeding grade ≥ 2
• 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). ] [ Designated as safety issue: No ]
  Skin lesion response rate in the double-blind period was determined only among patients with at least one skin lesion at baseline, and is the percentage of this group of patients with a best overall skin lesion response on the Physician's Global Assessment of Clinical Condition (PGA) of either complete clinical response (CCR) or partial response (PR).
• 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). ] [ Designated as safety issue: Yes ]
  Renal Impairment was measured by glomerular filtration rate which was calculated using the Modification of Diet in Renal Disease formula. Percentage of participants with renal impairment was reported.
• Change From Baseline in Plasma Angiogenic Molecules [ Time Frame: Baseline, 12 Months ] [ Designated as safety issue: No ]

• • Time to angiomyolipoma progression through MRIs at screening, 12, 24 and 48 weeks and annually thereafter [ Time Frame: Biomarkers assessed throughout the first year of the study only. All other outcomes are assessed through the duration of the study (5 years). ] [ Designated as safety issue: Yes ]
• • Skin lesion response rate tracked by digital photographs [ Time Frame: Biomarkers assessed throughout the first year of the study only. All other outcomes are assessed through the duration of the study (5 years). ] [ Designated as safety issue: Yes ]
• • Change from baseline in biomarkers collected during the first years of study [ Time Frame: Biomarkers assessed throughout the first year of the study only. All other outcomes are assessed through the duration of the study (5 years). ] [ Designated as safety issue: Yes ]
• • Changes in renal function by assessing creatinine clearance levels throughout the study [ Time Frame: Biomarkers assessed throughout the first year of the study only. All other outcomes are assessed through the duration of the study (5 years). ] [ Designated as safety issue: Yes ]
• • Safety assessed on a continuous basis throughout study [ Time Frame: Biomarkers assessed throughout the first year of the study only. All other outcomes are assessed through the duration of the study (5 years). ] [ Designated as safety issue: Yes ]

This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.

• Tuberous Sclerosis Complex (TSC)
• Lymphangioleiomyomatosis (LAM)

• Drug: Everolimus (RAD001)
  Everolimus is used in 5 mg strength tablets, blister-packed under aluminum foil in units of ten tablets and dosed on a daily basis. 10mg daily dosing throughout the trial.
  Other Name: RAD001
• Other: Placebo
  Matching placebo was provided as a matching tablet and was also blister-packed under aluminum foil in units of ten.

• Experimental: Everolimus
  Study drug was given by continuous oral daily dosing of two 5 mg tablets.
  Intervention: Drug: Everolimus (RAD001)
• Placebo Comparator: Placebo
  Placebo was given by continuous oral daily dosing of two 5 mg tablets.
  Intervention: Other: Placebo

Inclusion Criteria

• Male or Female 18 years or older
• Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
• Clinically definite diagnosis of renal angiomyolipoma
• At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
• Females of child bearing potential must use birth control and have documentation of negative pregnancy test
• Written informed consent according to local guidelines

Exclusion Criteria:

• Recent heart attack, cardiac related chest pain or stroke
• Severely impaired lung function
• Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
• Clinically significant chylous ascites
• Clinically significant hematological or hepatic abnormality
• Severe liver dysfunction
• Severe kidney dysfunction
• Pregnancy or breast feeding
• Current infection
• History of organ transplant
• Surgery within two months prior to study enrollment
• Prior therapy with a medication in the same class as Everolimus
• Recent use of an investigational drug
• Bleeding diathesis or on oral anti-vitamin K medication
• Uncontrolled high cholesterol
• Uncontrolled diabetes
• HIV
• Inability to attend scheduled clinic visits
• Patients with metal implants thus prohibiting MRI evaluations
• Angiomyolipoma which requires surgery at the time of randomization
• History of malignancy
• Severe or uncontrolled medical conditions which would cause an unacceptable safety risk or compromise compliance with the protocol

Other protocol-defined inclusion/exclusion criteria may apply