A Study to Determine the Safety and Effectiveness of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis

An Exploratory, Open-label, Non-randomized, Within-patient Multiple Dose-escalation Safety, Tolerability, PK and Efficacy Trial of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis

This was an exploratory study to determine whether escalating doses of RAD001 (everolimus) were safe and effective in patients with Lymphangioleiomyomatosis

In addition to the data collected in this study, historical data from 43 patients treated with placebo from the multicenter trial of sirolimus in LAM (MILES) study (NCT00414648) were down weighted to an effective sample size of 18 for comparison of FEV1 and FVC endpoints. Reference to the publication of the MILES study has been provided under "Result Publication".

Inclusion Criteria:

• Female aged >/= 18 years with a diagnosis of LAM
• Pulmonary function abnormalities as follows:
• FEV1 of ≤ 80% of the predicted value following administration of a standard dose of a short acting β2-agonist (*200 µg Salbutamol, measured between 10 and 15 minutes of inhalation) OR
• FEV1 < 90% of the predicted value of bronchodilator following administration of a standard dose of a short acting β2-agonist (*200 µg Salbutamol, measured between 10 and 15 minutes of inhalation) and DLco (uncorrected) <80% predicted.
• Female patients including those of childbearing potential will be included in this study.
• Negative pregnancy test at screening and baseline

Exclusion Criteria:

• FEV1<50% of predicted post-bronchodilator.
• Change in FVC (ml) > ± 15% of screening value at baseline visit (not less than 14d after screening visit).
• Use of any medicine containing estrogen in the 4 months prior to the screening visit and for the duration of the study
• Significant hematologic, renal, hepatic laboratory abnormality or amylase > 1.5x the upper limit of the normal range at the screening or baseline visits
• Fasting blood glucose > 126mg/dl or random blood glucose >200mg/dl at screening and/or baseline
• Recent surgery (involving entry into a body cavity or requiring sutures) within 2 months of the screening visit or any evidence of unhealed surgical wound.
• Uncontrolled hyperlipidemia (defined as persistent elevation of total cholesterol or triglycerides >6.5nM/L) or a history of clinical atherosclerotic disease including heart attack, angina, peripheral vascular disease or stroke.
• Previous organ transplantation
• Inability to give informed consent
• Inability to perform pulmonary function or 6 minute walk tests and imaging assessments

Other protocol-defined inclusion/exclusion criteria may apply