Current Research with Inclusion/Exclusion Criteria

Holzer Clinic Department of Research
Extension 3792/3990

BioSante –LibiGel
(Treatment of Hypoactive Sexual Desire in Postmenopausal Women)

5 Year Study

Inclusion:

1. Women, 50 years of age or older
2. Menopause either naturally (at least 12 months amenorrheic) or after a bilateral salpingo-oophorectomy prior to natural menopause. Subjects with hysterectomy only must meet the following menopause criteria: 50 to </= 54 years must be experiencing hot flushes or receiving estrogen therapy for hot flushes (if these subjects are asymptomatic they require a serum FSH 30 U/mL); 54 years is considered postmenopausal.
3. At least one risk factor for cardiovascular disease including:
1. Age of 70 years or greater
2. Type I diabetes or Type 2 diabetes (fasting glucose > 125 mg/dL or taking an anti-diabetic drug); subjects with diet-controlled Type II diabetes must have an HgbA1C >6.5%.
3. Presently smoking at least 10 cigarettes per day (or equivalent, e.g. chews tobacco daily)
4. Taking antihypertensive medication (for treatment of hypertension)
5. Taking lipid-lowering medication
6. Documented history of cardiovascular disease, ie. Myocardial infarction, stroke, hospitalization for unstable angina/acute coronary syndrome, revascularization of the coronary, carotid, or peripheral circulations. (Must be > 6 months before randomization)
4. A clinical diagnosis of HSDD

Exclusion:

1. Any clinically significant skin abnormalities in the area of study drug application
2. Requires treatment with any of the following:
• Anti-androgens
• Tamoxifen
• Other selective estrogen receptor modulators (treatment and prevention of osteoporosis is acceptable)
3. Taking androgen therapy within 2 months prior to Randomization (Visit 2)
4. History of major psychiatric illness:
• Schizophrenia
• Bipolar disorder, major depression, other psychoses under current treatment that have required medication adjustment within 2 years of Screening Visit 1
5. History of myocardial infarction, stroke, hospitalization for unstable angina/acute coronary syndrome, revascularization of the coronary, carotid, or peripheral circulations, within 6 months of randomization.
6. History of bleeding disorder serious enough to require regular transfusions
7. History of scleroderma

BioSante –LibiGel
(Treatment of Hypoactive Sexual Desire Disorder in Surgically Menopausal Women)

8 Month Study

Inclusion:

1. Is women, 30 to 65 years of age
2. Has undergone hysterectomy and bilateral salpingo-oophorectomy prior to natural menopause (i.e. subject was menstruating within 12 months prior to surgery). The bilateral oophorectomy must have been completed at least 6 months but not more than 15 years before Screening Visit 1.
3. Is taking a stable dose of estrogen therapy for at least 3 months before Screening Visit 1 and intends to continue that dose for the duration of the study.
4. Is in a stable, monogamous, heterosexual relationship that is perceived by the subject to be secure and communicative, for at least 1 year prior to Screening Visit 1.

Exclusion:

1. A history of allergic reactions to androgens (oral or patch), topical alcohol, or any component of the formulation.
2. Any systemic skin diseases or local skin abnormalities in the area of application
3. A medical condition that could affect or interfere with sexual function (e.g., depression, anxiety, other psychiatric illness, dyspareunia, painful intercourse not relieved by vaginal lubricants, or physical limitations).
4. Using a systemic topical gel or cream estrogen therapy
5. Taking any of the following medications: Coumadin, glucocorticosteroids (inhaled acceptable), any antidepressants or anti-androgens
6. A history of malignant melanoma

Pfizer Inc
(Study of Cardiovascular Safety in Osteoarthritis or Rheumatoid Arthritis Patients with or at High Risk for Cardiovascular Disease Comparing Celecoxib with Naproxen and Ibuprofen)

42 Months Study

Inclusion:

1. Men and women, 18 years if age or older at time of consent
2. Clinical diagnosis of OA or RA with a duration of at least 6 months
3. All subjects must have a required regimen for at least 6 months and taken chronic analgesic therapy > 50% of the time.
4. Subject with established or at high risk for CVD defined as one of the following:
• Coronary disease
• Occlusive disease of non-coronary arteries
• Diabetes mellitus: clinical diagnosis of Type I or Type II diabetes

Exclusion:

1. Acute joint trauma with active symptoms
2. Planned surgical or other invasive procedure to be performed during the course of the study
3. Receiving treatment with oral corticosteroids at a daily does > 20 mg prednisone or equivalent
4. Requires and is receiving treatment with >325 mg aspirin/day

Sanofi-aventis ACT11308
(Randomized, double-blind, placebo-controlled study of the effect of a single injection of SAR164877{REGN475} on reduction of pain from vertebral fracture associated with osteoarthritis)

6 Visit/12 Week Study

Inclusion:

1. Patients with moderate to severe pain due to non-traumatic vertebral fracture (VF) with onset of pain within the last 5 days.
2. Written Informed Consent.

Exclusion:

1. Vertebral pain at screening and randomization <5 on “worst pain” pain intensity-numeric rating scale (PI-NRS)
2. Narcotic addiction
3. Post-fracture vertebral instability that might require vertebral stabilization procedure
4. Unwillingness to use study-defined rescue analgesia exclusively
5. <40 years or >80 years of age at screening

Roche Human Papilloma Virus

2.5 Year Trial

Inclusion Criteria:

1. Female, age 18 years and older
2. Providing written informed consent
3. Using effective birth control practice – 2 methods of contraception, one of which must be barrier, should be used
4. Pap smear documenting ASCUS, ASC-H, LSIL, HSIL within 3 months of screening
5. Diagnosis within 2 months prior to first dose of study drug of CIN 2/3 confirmed by colposcopy-directed punch biopsy

Exclusion Criteria:

1. Have colposcopically visible CIN 2/3 disease extending over more than 2 quadrants
2. Have had any previous excisional or ablative surgical treatment for CIN
3. Have vulvar (VIN) or vaginal (VAIN) intraepithelial neoplasia
4. Have previously received a prophylactic HPV vaccine
5. Have a serious, concomitant disorder, including active systemic infection requiring treatment
6. Prior history of a current malignancy other than adequately treated skin cancer
7. Proven or suspected immunosuppressive disorder or autoimmune disease
8. Have any significant cardiac, hepatic or renal disease
9. Breast feeding
10. Known allergy to eggs

Johnson and Johnson Protocol 28431754-DIA-3008
(A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus {The CANVAS Trial: CANagliflozin CardioVascular Assessment Study})

4 Years Clinical Study with Possible 2-4 Years Following

Inclusion Criteria:

1. Man or woman between 30 to 85 years of age with a diagnosis of T2DM with HbA1c level = 7.0 to = 10.5% at screening
2. Women must be postmenopausal, surgically sterile, abstinent, or practicing a highly effective method of birth control throughout the study, as local regulations permit.
3. Women of childbearing potential must have a negative urine ß-hCG pregnancy test at the screening and baseline visits.
4. History or high risk of CV disease defined on the basis of either:
   • Age =30 years with a history of a previous CV event defined as 1 or more of the following that occurred at least 30 days before screening for study run-in: myocardial infarction, stroke, percutaneous coronary intervention (PCI) or coronary artery bypass graft, or acute coronary syndrome (treatment in a hospital or emergency room as a result of 1 or more episodes of ischemic discomfort at rest, with associated ECG changes)
   • Age =50 years with 2 or more of the following risk factors at screening: micro- or macro-albuminuria, duration of T2DM of 10 years or more, low-density lipoprotein (LDL)-cholesterol of >4 mmp;: (>154 mg/dL) on treatment with a statin and/or fibrate, high-density lipoprotein (HDL)-cholesterol of <1mmol/L (<39 mg/dL), systolic blood pressure >140 mmHg on at least 1 blood pressure lowering treatment, or current cigarette smoker (one half pack or more of cigarettes per day).
5. Subjects must have signed Informed Consent indicating they understand the purpose of and procedures required for the study and are willing to participate in the study and abide by the restrictions specified in the protocol.

Exclusion Criteria:

1. Diagnosis of type 1 diabetes or prior history of ketoacidosis
2. Major CV event or cerebral or coronary revascularization within 30 days before screening for study run-in or a revascularization procedure planned for within 6 months after screening for study run-in, or clinical diagnosis of heart failure of New York Heart Association (NYHA) Class IV
3. Clinical diagnosis of significant renal impairment (eGFR <50 mL/min/1.73m²) or history of renal transplantation
4. ALT and AST levels >2.0 times the upper limit of normal or total bilirubin >1.5 times the upper limit of normal, at screening, unless in the opinion of the investigator and as agreed upon by the sponsor’s medical officer, the findings are consistent with Gilbert’s disease.
5. Any factor that in the opinion of the investigator would preclude a life expectancy of at least 1 year, may influence compliance with the study drug, or otherwise lead to incomplete adherence to the study protocol
6. History of malignancy within 5 years before screening (except squamous and basal cell carcinomas and cervical carcinomas in situ)
7. Any of the following:
   • concurrent use of any other SGLT2 inhibitor
   • an investigational drug within 4 weeks of the screening visit
   • rosiglitazone within 13 weeks before or following the screening visit
   • digoxin at the time of or following the screening visit
   • prior exposure to JNJ-28431754
   • known or anticipated allergies, hypersensitivity, or intolerance to JNJ-28431754 or its excipients

Salix Pharmaceuticals, Inc. Protocol BUCF3001

(A phase III, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of Budesonide Foam {2mg/25ml BID for 2 weeks, followed by 2mg/25ml QD for 4 weeks} versus placebo in subjects with active mild to moderate ulcerative proctitis or proctosigmoiditis)

Study will last up to 11 weeks

Inclusion Criteria:

1. Subject understands the language of the informed consent and is capable and willing to sign the informed consent form.
2. = 18 and =75 years of age
3. Male or female. Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include double barrier methods (condom with spermicide jelly or diaghragm with spermicide), hormonal methods (oral contraceptives, patches, or medroxyprogesterone acetate), or an intrauterine device (IUD) with a documented failure rate of less than 1% per year. Abstinence may be considered an acceptable method of contraception at the discretion of the investigator. Females who have been surgically sterilized or who are postmenopausal (total cessation of menses for >1 year) will not be considered “females of childbearing potential”.
4. Subjects with confirmed diagnosis of active, mild to moderate, ulcerative proctitis or proctosigmoiditis, with disease extending at least 5 cm but no further that 30 cm from the anal verge. The following criteria must apply:
   • Diagnosis must be confirmed by endoscopy with easy passage of the endoscope to at least 10 cm above the proximal of the disease
   • NOTE: a subject must undergo colonoscopy at baseline if a previous colonoscopy procedure has not been performed within 12 months of the screening date
   • Subjects newly diagnosed with active, mild to moderate, ulcerative proctitis or proctosigmoiditis must have had symptoms (e.g. rectal bleeding) for at least 45 days prior to screening and must undergo colonoscopy to confirm diagnosis.
   • For initial diagnosis, a pathological report from a local pathologist identifying histological changes characteristic of UP/UPS will be required to meet eligibility requirements.
5. Subjects must possess a baseline MMDAI score between 5 and 10, inclusive. Subjects must score =2 on the MMDAI rectal bleeding component and =2 on the MMDAI endoscopy or sigmoidoscopy component at Randomization to be eligible.
6. Subject is capable of understanding the requirements of the study, is willing to comply with all the study procedures including diary completion and is willing to attend all study visits.

Exclusion Criteria: (NOTE: development of any of the following exclusion criteria during the study may be considered a basis for discontinuation)

1. History of ulcerative colitis extending more proximally that 35 cm from anal verge, or diagnosis of Crohn’s disease or indeterminate colitis
2. Prior gastrointestinal surgery except appendectomy and hernia. (Prior cholecystectomy is not exclusionary if greater than one year prior to Screening.)
3. Diagnosis of one or more significant co-morbid condition(s), including:
   1. Concomitant active gastrointestinal disease, to include duodenal ulcer, gastric ulcer, erosive gastritis or erosive esophagitis (Los Angeles Class B,C, or D)
   2. History of sclerosing cholangitis, cirrhosis, or hepatic impairment, including chronic hepatitis of any etiology.
   3. History of diverticulitis, collagenous colits, celiac disease, recurrent pancreatitis, or know gallbladder disease.
   4. Distortion of intestinal anatomy, such as small bowel, rectal or colonic stricture.
   5. Diabetes mellitus (Type 1 or 2) requiring medication, or a fasting blood glucose =126mg/dL taken at Screening.
   6. History of abnormal thyroid function not controlled by thyroid medications.
   7. Unstable significant cardiovascular, endocrine, neurologic or pulmonary disease. Subjects with hemoglobin levels <7.5 g/dL are also excluded.
   8. Hepatic disease manifested by 1.5 times the ULN for any of the following liver function tests: ALT, AST, Alk P or total bilirubin.
   9. Renal disease manifested by >2.0mg/dL serum creatinine.
   10. History of avascular necrosis of the hip.
   11. History of active tuberculosis or ocular herpes simplex or ocular varicella zoster.
   12. History of malignant disease with the following exceptions: basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.
   13. History or diagnosis of HIV, any other immunosuppressed condition, or hepatitis B or C.
   14. Adrenal insufficiency
   15. Active systemic or cutaneous infection, including parasitic disease, at study entry.
   16. History of or current diagnosis of toxic megacolon, fistula, perforation or abscess.
   17. Subject has history of psychiatric disorders which are not controlled (includes significant depression or suicidal ideation; controlled is based on the investigator’s medical judgment); subjects with psychoses are excluded regardless of current therapy.
   18. Subject has history of seizure disorders
   19. Subjects with asthma requiring inhaled steroids within the past 3 months to Screening Visit.
   20. Subject has current or recent history of drug or alcohol abuse.
   21. Subject is pregnant or lactating.
4. Subject has a positive stool test for bacterial pathogens, C difficile toxin or ovum and parasites.
5. History of receiving any type of vaccination within the past 28 days prior to Randomization.
6. Subject has any condition or circumstance that could cause noncompliance with treatment or visits.
7. Subject has known allergy to budesonide or to excipients and/or vehicles used in the formulation preparation.
8. Subject has participated in an investigational drug or device study within the 30 days prior to signing informed consent.
9. Subject is an employee of the site that is directly involved in the management, administration, or support of this study or is an immediate family member of the same.
10. The following medications (and/or medication history) are not permitted within the timepoints specified:
    • History of treatment with a cell-depleting therapy
    • Any type of vaccination during the study
    • Anti-seizure and antipsychotic drugs
    • Concomitant use of diuretics with cardiac glycosides
    • Within 6 months of screening: Drugs used for the treatment of IBS
    • Within 3 months of Screening: Inhaled corticosteroids. Subjects with asthma requiring use of intermittent inhaled steroids within the past 6 months are excluded
    • Within 60 days of Screening: Immunosuppressants; Anticoagulants
    • Within 30 days of Screening: Systemic, oral, topical, or rectal corticosteroids, including budesonide
    • Subjects taking any investigational agents
    • Within 14 days of Screening: Antibiotics, Antispasmodics and prokinetic drugs, Laxatives and enemas, Narcotics
    • At the Screening Visit: Ketoconazole and other potent CYP3A4 inhibitors
    • At the Run-In/Stabilization Visit: Rectal 5-ASA products; Antidiarrheals; Subjects taking supplement or products specifically marketed as probiotics; Routine use of NSAIDS, with the exception of cardioprotective aspirin