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

A Multicenter, Dose-finding Study to Determine if Oral BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in Elderly Subjects

The purpose of this study is to evaluate the efficacy, tolerability, and safety of BEZ235 alone and in combination with RAD001 to support further development to reduce the incidence of respiratory tract infections (RTIs) in elderly subjects.

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.