An Exploratory, Open Label, Non-randomized, Within-patient Multiple Dose-escalation Safety, Tolerability, PK and Efficacy Trial of RAD001 (Everolimus) in Patients With Lymphangioleiomyomatosis
- 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
- 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
- Negative pregnancy test at screening and baseline
- 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
- 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
Other protocol-defined inclusion/exclusion criteria may apply