A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly

Exclusion Criteria

• •1. Any subject who:
• •* Is a current smoker as assessed by medical history or a positive serum cotinine test (or positive urine cotinine test if serum cotinine testing is unavailable) at Screening. Stopped smoking ≤1 year prior to Screening.
• •* Is a previous smoker with a ≥10 pack year smoking history. Has a household member who currently smokes in the house
• •2. Subjects with a medical history of clinically significant lung diseases other than asthma (e.g., chronic obstructive pulmonary disease (COPD), emphysema, interstitial pulmonary fibrosis (IPF), bronchiectasis, etc.).
• •3. Subjects with a Mini Mental Status Examination (MMSE) score \<24 at Screening.
• •4. Subjects with current evidence of a serious and/or unstable medical disorder including cardiovascular, respiratory, gastrointestinal, renal (including subjects with an estimated glomerular filtration rate (eGFR) as estimated by the modified diet in renal disease (MDRD) GFR equation that is ≤30 mL/min/1.73m2), or hematologic disorders.
• •5. The following cardiac conditions:
• •* Unstable angina pectoris or acute ischemic changes on ECG at Screening or Baseline
• •* History of myocardial infarction (MI), coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening
• •* New York Heart Association functional classification IIIIV congestive heart failure
• •* Unstable or life-threatening cardiac arrhythmia, chronic stable atrial fibrillation is allowed.
• •* QTcF\>480 msec at Screening or Baseline
• •6. Subjects with 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 (AJCC stage T2N0M0 or better).
• •* Cervical carcinoma in situ.
• •* Breast cancer localized to the breast.
• •7. Any RTI or acute significant illness (based on the subject's medical history and the clinical judgement of the Investigator) which has not resolved at least two (2) weeks prior to Baseline.
• •8. Subjects with a history of systemic autoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), or receiving immunosuppressive therapy (such as mycophenolate, tacrolimus, cyclosporine, azathioprine, infliximab) including chronic use of prednisone \>10 mg daily (however, inhaled corticosteroids and the acute use of higher doses of prednisone to treat conditions such as exacerbation of asthma or other acute conditions are allowed).
• •9. Subjects with Type I diabetes mellitus.
• •10. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation.
• •11. Subjects with any one of the following during Screening:
• •* white blood cell (WBC) count \<2.0 x103/microL.
• •* neutrophil count \<1.0 x 103/microL.
• •* platelet count \<75 x 103/microL..
• •12. Subjects with a history of alcohol or drug abuse within 2 years of the Screening visit.
• •13. Subjects with any conditions affecting absorption, distribution, or metabolism of the study drug (e.g., inflammatory bowel disease, gastric or duodenal ulcers, or hepatic disease). For subjects with biochemical evidence of liver injury as indicated by abnormal liver function tests:
• •* Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN) in subjects who do not have Gilbert's syndrome. If the subject has a history of Gilbert's syndrome, direct and indirect reacting bilirubin should be differentiated, and the direct bilirubin must be less than 1.5 x ULN.
• •* Any elevation above ULN of more than one parameter of ALT, AST, alkaline phosphatase or serum bilirubin will exclude a subject from participation in the study.
• •14. Subjects with a history of immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result.
• •15. Infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
• •16. Subjects who require treatment with strong CYP3A4 or CYP1A2 inhibitors or inducers, or subjects who require treatment with digoxin.
• •17. Use of any other investigational medication or participation in any other investigational study within 5 half-lives of the investigational medication, or within 30 days, whichever is longer; or longer if required by local regulations.
• •18. Subjects who have received an organ transplant.
• •19. Subjects who previously received treatment with RTB101 in another clinical study (e.g., CBEZ235Y2201, RTB-BEZ235-202, or RTB-101-203).