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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Respiratory Tract Infections

Intervention / Treatment
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* Other: Placebo
* Drug: BEZ235
* Drug: BEZ235 plus everolimus (RAD001)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo once daily for 16 weeks<br> | Other: Placebo<br>* oral<br>|
| Experimental: BEZ235 once daily for 16 weeks<br> | Drug: BEZ235<br>* oral<br>|
| Experimental: BEZ235 twice daily for 16 weeks<br> | Drug: BEZ235<br>* oral<br>|
| Experimental: BEZ235 plus RAD001 once daily for 16 weeks<br> | Drug: BEZ235 plus everolimus (RAD001)<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects with 1 or more laboratory-confirmed RTIs through Week 16 |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects who develop one or more RTIs through week 16 |  | 16 weeks | 
| The rate of RTIs/person through week 16 |  | 16 weeks | 
| The rate of RTIs per person through week 24 |  | 24 weeks | 
| The percentage of subjects with 1 or more laboratory-confirmed RTIs through week 24 |  | 24 weeks | 
| Peak Plasma Concentration (Cmax) |  | 8 weeks | 
| Area under the plasma concentration versus time curve (AUC) |  | 8 weeks |