Dose Finding Study to Determine if BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in the Elderly

This is a randomized, blinded, placebo-controlled, multicenter, parallel-group, dose finding 24-week study to assess the safety, tolerability and efficacy of up to 3 doses of BEZ235 alone and in combination with RAD001 as compared to placebo in elderly subjects who are at increased risk of respiratory tract infection related-morbidity and mortality. The study will be composed of up to a 6-week screening and run-in period, a 16-week treatment period and an 8-week follow-up period.

Inclusion criteria

• Male and female subjects
• Age ≥ 85 years
• Age ≥ 65 and < 85 years with one or more of the following conditions:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Chronic bronchitis
• Type 2 Diabetes Mellitus (T2DM)
• Congestive Heart Failure (CHF) New York Heart Association (NYHA) functional classification I-II
• Current smoker
• One or more emergency room visits or hospitalizations for a RTI during the previous 12 months

Exclusion criteria

• Subjects with medically significant cardiac conditions including NYHA functional classification III-IV
• Subjects with Type I diabetes mellitus.
• Subjects with clinically significant underlying pulmonary disease other than asthma, GOLD Class I and II COPD or chronic bronchitis
• History of malignancy in any organ system within the past 5 years except for the following:

• Localized basal cell or squamous cell carcinoma of the skin, prostate cancer confined to the gland, cervical carcinoma in situ, breast cancer localized to the breast.
• Subjects with any one of the following:

• hemoglobin < 10.0 g/dL for males and < 9.0 for females
• white blood cell (WBC) count < 3,500/mm3,
• neutrophil count < 2,000/mm3
• platelet count < 125,000/mm3
• Subjects with a history of a systemic autoimmune disease or receiving immunosuppressive therapy
• Recent surgery other than minor skin surgery
• Liver disease or liver injury
• History or presence of impaired renal function
• History of immunodeficiency diseases
• Subjects with active infection
• Subjects with a Mini Mental Status Examination (MMSE) score <24 at screening.
• Significant illness (based on the subject's medical history and the clinical judgement of the investigator) which has not resolved within two (2) weeks prior to initial dosing.