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

Eli Lilly and Company
(A Comparison of Prasurgrel and Clopidogrel in Acute Coronary Syndrome {ACS} Subjects with Unstable Angina/Non-ST-Elevation Myocardial Infarction {UA/NSTEMI} Who are Medically Managed – The TRILOGY ACS Study)

30 Months Study

Inclusion:

1. Male or female, 18 years or older who have had a UA/NSTEMI index event within 10 days (240 hours) prior to randomization.
2. Have had a medical management strategy decision made with reasonable certainty; that is, neither PCI nor CABG is planned for treatment of the index event.
   • For subjects whose medical management decision and randomization occurs no later than 72 hours following onset of the index event, prior to clopidogrel treatment is not a consideration for eligibility.
   • For subjects with a medical management decision who are randomized beyond 72 hours of onset of the index event, clopidogrel must be administered according to standard of care practice for ACS patients no later than 72 hours following the onset of the index event:
3. Have had at least one of the following 4 high-risk features at the time of the UA/NSTEMI event:
   • Age = 60 years
   • Prior MI evidenced by pre-existing Q waves, or demonstration of infarction on imaging studies, or prior documentation of elevated cardiac markers
   • Diabetes Mellitus – defined by concomitant treatment with an oral hypoglycemic agent and/or insulin
   • Coronary revascularization (either PCI or CABG) at least 30 days before the onset of the index ACS event

Exclusion:

1. Decision for medical management = 72 hours after the onset of the index event without commercial clopidogrel treatment within 72 hours following the onset of the index event (Note: commercial clopidogrel treatment must continue daily thereafter until randomization).
2. Planned PCI or CABG as treatment for the index ACS event-either during the index hospitalization or thereafter.
3. PCI or CABG performed within the previous 30 days.
4. STEMI as the index event.
5. Cardiogenic shock within the previous 24 hours (defined as a systolic blood pressure =90 mm Hg associated with clinical evidence of end-organ hypoperfusion, or hypotension requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion)
6. Refractory ventricular arrhythmias within the previous 24 hours.
7. Symptoms of New York Heart Association (NYHA) Class IV congestive heart failure (CHF) within the previous 24 hours
8. Clinical findings associated, in the judgment of the investigator, with an unacceptably high risk of bleeding
9. Any of the following:
   • History of ischemic or hemorrhagic stroke
   • Intracranial neoplasm, arteriovenous malformation, or aneurysm
   • History of any TIA symptoms
10. History of spontaneous gastrointestinal or non-gastrointestinal internal bleeding requiring in-hospital treatment, unless the event has been definitively treated and, in the investigator’s opinion, has a low likelihood of recurrence.
11. Currently receiving hemodialysis or peritoneal dialysis
12. Females who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
13. Females of childbearing potential (that is, females who are not surgically or chemically sterilized and who are between menarche and 1-year post menopause) and do not agree to use a reliable method of birth control during the study.
14. Known severe hepatic dysfunction (that is, with cirrhosis or portal hypertension).
15. Insignificant coronary disease identified during coronary angiography performed for the index ACS event (defined as the absence of at least one stenosis in any native coronary artery visually estimated to be =30%).

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

Sanofi-aventis ACT11286

(A randomized, double-blind, placebo-controlled study of the effect of a single injection of SAR164877 {REGN475} on reduction of pain from chronic pancreatitis)

Study will last 12 weeks

Inclusion Criteria:

1. Patients with moderate to severe abdominal pain due to Chronic Pancreatitis of at least 6 months duration and a frequency threshold of at least 2 episodes per month in the preceding 3 months requiring analgesia, or at least 1 episode of severe pain requiring pain management in an emergency room or hospitalized setting in the preceding 3 months.
• Chronic Pancreatitis confirmed by at least one of the following:
• Histological confirmation
• Computerized Tomography/Magnetic Resonance Imaging (including calcifications, dilated ducts, dilated main pancreatic duct and/or atrophy)
• Endoscopic retrograde pancreatogram with Cambridge grade (18) of 3 or greater
• Endoscopic ultrasound
2. Written Informed Consent obtained

Exclusion Criteria:

1. over 18 years or under 80 years of age at screening
2. Abdominal pain at screening (visit 1) or randomization (visit 2) of <5 on "worst pain" PI-NRS
3. Intervention specifically indicated for relief of chronic pancreatitis pain performed within the past 6 months before screening (visit 1) or planned within 4 months after screening.
4. Cholelithiasis or biliary obstruction
5. Severe Steatorrhea (defined as 24 hr quantitative fat >14% as performed within last 6 months prior to randomization)
6. Known pancreatic carcinoma
7. Current pancreatic pseudocyst (unless documented as unchanged for =12mos)
8. Known splenic vein thrombosis
9. Uncontrolled diabetes
10. Narcotic, solvent or alcohol addiction and/or abuse in the Investigator’s judgment based on medical history and physical exam
11. High degree of somatization
12. Moderate severe major depression
13. Weight loss =10% of ideal body weight within last 6 months
14. Triglycerides >1000 mg/dL at either screening or randomization visits.
15. Daily opiate requirement (in the opinion of the investigator, the character of the patient’s pain requires use of a daily opioid)
16. Prior and/or concomitant use of the following agents with pain relieving properties is prohibited as follows:
• Concomitant use of an immediate release opioid or other non-protocol specified analgesic at any time during the study; if used prior to screening must be able to be washed out prior to randomization.
• Use of long acting or controlled release opioid within last 30 days before screening or concomitant use at any time during the study
• Introduction of an anti-convulsant, monoamine oxidase inhibitor, tricyclic antidepressant, neuropleptic or SSRI within 30 days of screening or new concomitant use at any time during the study
• Use of a systemic corticosteroid within last 7 days before screening or concomitant use at any time during the study
17. Prior and/or concomitant use of the following agents with potential pain relieving properties are restricted as follows:
• Use of cardiovascular prophylaxis dose of ASA for less than 14 days before screening visit
• Use of the following agents is allowed as long as, in the Investigator’s judgment, the use was stable for at least 3 months prior to screening visit:
1. pancreatic enzyme replacement
2. acid reducing agent
3. oral contraceptive
4. antioxidants
5. oral anti-diabetic medications/insulin
18. Any history of or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, or infectious disease that could interfere with the conduct of the study as judged by the Investigator.
19. Unable to use study defined rescue analgesia (acetaminophen) for any reason
20. Known sensitivity to doxycycline or mAb therapeutics
21. Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives, whichever is longer, of the investigational drug prior to the Screening Visit.
22. Previous exposure to an anti-NGF antibody within 6 months of enrollment in this study
23. Women who are pregnant or nursing
24. All female patients will be considered "women of childbearing potential" unless they have undergone a verifiable surgical sterilization procedure or are post-menopausal; women must be amenorrheic for at least 12 months in order to be considered post-menopausal. Women of childbearing potential with either a positive pregnancy test result or no pregnancy test at screening or randomization.
25. Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study and for 3 months following the end of the study.

Pfizer A4091044

(A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of the Analgesic Efficacy and Safety of Tanezumab in Patients with Chronic Pancreatitis)

Study will last 20 weeks

Inclusion Criteria:

1. Patients must consent in writing to participate in the study by signing and dating an Informed Consent document.
2. Male or female of any race, = 18 years of age.
3. Diagnosis of chronic pancreatitis based on morphologic changes observed on imaging. Acceptable imaging studies include MRI, CT scan, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography (ECRP) or magnetic resonance cholangiopancreatography (MRCP). New images should be obtained if a patient has had worsening of their pain or deterioration in their status which suggests acute obstruction, pseudocyst(s) or pancreatic cancer.
4. Persistent abdominal pain due to chronic pancreatitis for at least 3 months immediately prior to Screening.
5. All concomitant medications including medications for the management of chronic pancreatitis pain are at a stable dose and regimen for at least 30 days prior to Screening and are expected to remain at a stable dose and regimen throughout the study.
6. Completes at least 6 daily pain diaries during the 7 days prior to Randomization.
7. Female patients must meet one of the following criteria:
1. Female of non-childbearing potential: post menopausal (women who are =45 years old with amenorrhea for 24 consecutive months; amenorrhea for at least 1 year AND have a serum FSH level greater than 30 IU/L at Screening; or surgically sterile).
2. Female patients of child-bearing potential: must not be pregnant or lactating and must be abstinent or use adequate contraception (2 forms of birth control, one of which must be a barrier method).
3. Male patients must agree that they and their female spouses/partners will use adequate contraception (2 forms of birth control, one of which must be a barrier method) or be of non-childbearing potential.
4. Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of screening procedures until 16 weeks after study medication administration.
8. Patients must be willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, lab tests and other study procedures.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

1. Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to become pregnant during the course of the clinical study
2. Chronic pancreatitis as a complication of pancreatic cancer or acute pancreatic duct obstruction
3. Pancreatic surgery, lithotripsy, or endoscopic decompression within 3 months of screening
4. History of alcohol abuse within 1 year of Screening or concurrent alcohol abuse (defined as =35 alcoholic drinks/week)
5. Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with chronic pancreatitis
6. Body mass index of >39 kg/m2
7. Planned surgical procedure during the study
8. History of cancer within the last 5 years except for cutaneous basal cell or squamous cell cancer resolved by excision
9. Signs and symptoms of clinically significant cardiac disease including but not limited to:
1. Ischemic cardiac disease
2. Surgery or stent placement for coronary artery disease in the 6 months prior to screening
3. Heart failure (New York Heart Association Class III or IV congestive heart failure or known left ventricular dysfunction with ejection fraction =35%, cardiomiopathy, myocarditis in the 6 months prior to Screening)
4. Resting tachycardia or resting bradycardia on ECG at Screening or Baseline
5. QTcF interval >500 msec in the absence of confounding factors like bundle branch block or paced rhythm at Screening or Baseline
6. Any other cardiovascular illness that in the opinion of the Investigator would render a patient unsuitable to participate in the study
7. NOTE: Patients with a history of heart block now controlled by a functioning cardiac pacemaker and/or transient episodes of asymptomatic tachy- or brady- arrhythmias are eligible
10. Diagnosis of transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits that would preclude completion of required study activities
11. History, diagnosis or signs and symptoms of clinically significant neurological disease, including but not limited to:
1. Alzheimer’s disease or other types of dementia
2. Clinically significant head trauma within the past year
3. Peripheral neuropathy
4. Multiple sclerosis
5. Epilepsy or seizure
6. Myopathy
12. Patients with a past history of carpal tunnel syndrome with signs or symptoms of CTS in the 1 year prior to Screening
13. Present (current) history of sciatica (patients with a past history of sciatica who have been asymptomatic for at least 1 year and who have no evidence of radiculopathy or sciatic neuropathy on thorough neurologic exam may be considered for study)
14. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder
15. Previous exposure to exogenous NGF or to an anti-NGF antibody
16. History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein
17. Resting, sitting BP =160 mm Hg in systolic pressure or =100mm Hg in diastolic pressure at Screening
18. ALT or AST =3.0 times the upper limit of normal, creatinine exceeding 1.7 mg/dL in men or 1.5 mg/dL in women, or hemoglobin A1c =10% at Screening. Repeat confirmatory tests may be performed.
19. Presence of drug abuse (including prescription medications without a valid prescription), other illegal drugs or marijuana in the urine toxicology screen obtained at screening
20. Non-zero blood alcohol test result at Screening
21. Positive Hepatitis B, Hepatitis C, or HIV tests at Screening
22. Use of biologics including any live vaccines within 3 months of IPAP or use during the study; vaccinations for influenza with inactive/killed virus and Pneumovax are allowable exceptions
23. Use of any investigational medication within 30 days prior to Baseline or plans to receive an investigational medication other than the study medication during the course of this study.
24. Other severe acute or chronic medical or psychiatric condition or lab abnormality that may increase the risk in the judgment of the investigator.

Athena D.U.E.T.S. Protocol PMT-4-001

(Athena PMT – Device to Treat Urinary–incontinence - Effectiveness, Tolerability, and Satisfaction “Athena DUETS Trial”)

Study consists of 5 visits over 13 weeks

Inclusion Criteria:

1. Women between the ages of 30 and 70 years
2. Suffer from urge-incontinence, stress incontinence or incontinence of mixed etiology and who may benefit from strengthening Kegel muscles by electrical stimulation
3. Able to perform informed consent and physically able to comply with protocol requirements
4. Experience one or more incontinence episodes per week
5. Women of childbearing potential must have a negative urine or blood pregnancy test within 7 days prior to initiation of treatment
6. Subject may be post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (e.g., hormonal contraceptive, intra-uterine device [IUD], diaphragm with spermicide, condom with spermicide or abstinence) from the screening visit through the duration of study participation
7. Have a positive response to two or more questions on the Athena Questionnaire

Exclusion Criteria:

1. Neurological deficiency that does not permit proper sensory perception or stimulation
2. Is currently pregnant, lactating or attempting to get pregnant
3. Has a cardiac pacemaker or a history of rate or conductive disturbance
4. Has anatomical vaginal structures that do not permit proper and complete placement of the trainer
5. Has irregular menstrual bleeding cycles
6. Has urinary or vaginal infections, localized lesions, or other undiagnosed symptoms
7. Has a history or symptoms of urinary retention
8. Has cancer or life expectancy of less than one year
9. Recreational drug use
10. Consume more than 3 caffeine beverages daily
11. Consume more that 1-2 alcoholic drinks per day
12. Significant drug use (causing dieresis or urinary retention)
13. Allergy or sensitivity to materials in the Athena PMT
14. Participation in another clinical trial within past 3 months
15. Subjects morbidly obese (BMI >35)
16. Subject who chronically smoke (>10 cigarettes per day)
17. Subjects required to do heavy lifting (>40 lbs regularly)
18. Surgery within the past six months for incontinence, or use of other incontinence devices
19. Currently taking cholinergic or anti-cholinergic drugs or other prescription or non-prescription drugs that may increase or decrease the volume or frequency of urination and thus, may confound the results of this study, except, in the opinion of the investigator. The subject’s regimen has been stable for at least sixty days.
20. Suspected infection or condition (e.g., diabetes) that would alter the subjects ability to participate or would confound the results of the trial.

Sanofi-aventis EFC11319

(A randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate cardiovascular outcomes during treatment with lixisenatide in type 2 diabetic patients after an Acute Coronary Syndrome)

Study duration estimated to be approximately 41 months; median duration is expected to be approximately 23.5 months

Inclusion Criteria:

1. Men and women who experienced an ACS event (i.e., ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarcation [NSTEMI] or unstable angina [UA] at least 5 days and no more than 12 weeks prior to the screening visit, and providing that they are discharged from the acute care facility.
2. Patients with history of type 2 diabetes prior to the screening visit.
3. Written informed consent obtained.

Exclusion Criteria:

1. HbA1c <60.0% or >10.0% on last value obtained prior to the screening visit.
2. Fasting Plasma Glucose >13.9 mmol/L (>250 mg/mg/dL) on last value obtained prior to the screening visit.
3. At the time of screening, age < 30 years.
4. Women of childbearing potential with no effective contraceptive method. Women of childbearing potential must have a confirmed negative serum pregnancy test at screening visit. They must use an effective contraceptive method throughout the study and agree to repeat serum pregnancy test at designated visits.
5. Type I diabetes mellitus
6. Use of GPL-1 receptor agonists or DPP-IV inhibitors within 3 months prior to the screening visit.
7. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC.
8. History of metabolic acidosis, including diabetic ketoacidosis within 6 months prior to screening.
9. Known history of drug or alcohol abuse within 6 months prior to the time of screening.
10. Patients who have undergone a coronary artery bypass graft surgery (CABG) prior to screening, or a percutaneous coronary intervention (PCI) within 30 days prior to screening or a catherization within 7 days prior to screening.
11. Patients with planned revascularization procedure (PCI or CABG) at the time of screening visit.
12. Conditions/situations such as:
• Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any cub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases
• Patients considered by the Investigator or any sub-Investigator as inappropriate for this study for any reason, e.g.
• Those deemed unable to meet specific protocol requirements, such as scheduled visits or being able to do self-injections
• Those with likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol
• Investigator or any sub-Investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc.
13. Patients who have previously participated in any clinical trial with lixisenatide.
14. Patients who have taken other investigational drugs within 1 month or 5 half lives, whichever is longer.

Additional Exclusion Criteria at the end of the run-in period (before randomization)

15. Informed consent withdrawal
16. HbA1c < 6.0% or > 10.0% measured at screening Visit.
17. Fasting Plasma Glucose >13.9 mmol/L measured at screening visit.
18. Patients with planned revascularization procedure at the time of baseline visit.
19. Lab findings measured at screening:
• Amylase and/or lipase > 3 times ULN
• Total bilirubin: > 1.5 x ULN (except in case of Gilbert’s syndrome)
• Hemoglobin <11 g/dL and/or neutrophils <1,500/mm3 and/or platelets <100,000/mm3
• ALT > 3x ULN
• Calcitonin = 20pg/ml
• Positive serum pregnancy test in females of childbearing potential
20. Lack of compliance during the placebo run-in period
21. Patients with any adverse event (AE) which, by the judgment of the Investigator would preclude participation in the study.

Exclusion Criteria related to the current knowledge of lixisenatide

22. Pregnancy or lactation
23. History of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, and unstable and not controlled gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the screening visit.
24. Allergic reaction to any GLP-1 receptor agonist or to metacresol in the past.
25. Severe chronic renal insufficiency

PPD/GSK GLP114130 Harmony

(A Randomized, Double-Blind, Active-Controlled, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of Albiglutide as Compared With Sitagliptin in Subjects With Type 2 Diabetes Mellitus With Renal Impairment)

Study duration is approximately 60 weeks

Inclusion Criteria:

1. Male or female, 18 years of age or older, who is renally impaired with a historical diagnosis of type 2 diabetes mellitus and is experiencing inadequate glycemic control on their current regime of diet and exercise or their antidiabetic therapy of metformin, TZD, SU, or any combination of these oral antidiabetic medications.
2. BMI =20 kg/m2 and =45 kg/m2
3. Fasting C-peptide =0.8 ng/mL
4. HbA1c between 7.0% and 10.0%, inclusive, at Visit 5.
5. For the regular use of other medications (does not include medications excluded by the protocol), it is preferred that the subjects are receiving a stable dose for at least 4 weeks before Screening.
6. Use of oral or systemically injected glucocorticoids is generally not allowed within 3 months before randomization; short courses of oral steroids (single dose or multiple doses for up to 2 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, and topical corticosteroids are allowed.
7. Hemoglobin =10 g/dL for male subjects and =9 g/dL for female subjects
8. GFR =15 mL/min and <90 mL/min using the MDRD formula
9. Thyroid stimulating homone level is normal or clinically euthyroid as demonstrated by further thyroid tests
10. Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study including the 8-week Posttreatment Follow-up Period.
11. Able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor
12. No major illness or debility that in the investigator’s opinion prohibits the subject from actively participating in their diabetes management and completing the study
13. Able and willing to provide written informed consent

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study.

1. History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.)
2. History of treated diabetic gastroparesis
3. Current ongoing symptomatic biliary disease or history of pancreatitis
4. History of significant gastrointestinal surgery, including gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function
5. Recent clinically significant cardiovascular and/or cerebrovascular disease including but not limited to the following:
1. Previous history of stroke or transient ischemic attack within 1 month before Screening. Subjects who are deemed clinically stable by the investigator may be enrolled 1 month after the cerebrovascular event
2. Acute coronary syndrome, which includes the following:
• Documented MI within 2 months before Screening and during the period up until receiving the first dose of study medication
• Any cardiac surgery within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable angina not responsive to nitroglycerin within 2 months before Screening and during the period up until receiving the first dose of study medication
3. Unstable cardiac rhythm, however, as an example, controlled atrial fibrillation is allowed
4. For subjects taking a TZD, current history of heart failure (NY Heart Association Class I to IV); for subjects not taking a TZD, current history of heart failure (NY Heart Association Class II to IV)
5. Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg
6. QTc interval >470 ms confirmed by a central reader at screening.
6. Hemoglobinopathy that may affect determination of Hb A1c
7. History of human immunodeficiency virus infection
8. History of total bilirubin >1.5 x ULN unless the subject has a previously known history of Gilbert’s syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin
9. ALT or aspartate aminotransferase (AST) >2.5 x ULN3
10. Fasting triglyceride level >850 mg/dL at Screening
11. Acute symptomatic (within 3 months before Screening) infection with Hepatitis B or Hepatitis C; however subjects with past or chronic Hepatitis B or Hepatitis C are allowed provided the requirements for ALT, AST, and total bilirubin are met
12. History of a psychiatric disorder that will affect the subject’s ability to participate in the study
13. History of alcohol or substance abuse within 1 year before screening
14. Positive urine drug screen at Screening unless the subject is taking a medically approved medication for which a positive drug screen simply verifies the sue of this medication
15. Female subject is pregnant, lactating, or <six weeks postpartum
16. Known allergy to any GLP-1 analogue, sitagliptin, other study medications’ excipients, excipients of albiglutide, or Baker’s yeast
17. History of type I diabetes mellitus, diabetic complications that in the opinion of the investigator would preclude effective participants in the study, or a history of ketoacidosis or hyperosmolar coma
18. Contraindications for the use of either background or potential randomized study medication
19. Receipt of any investigational drug or sitagliptin within the 30 days or 5 half-lives, whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization or receipt of albiglutide in previous studies
20. History or family history of medullary carcinoma
21. History or family history of multiple endocrine neoplasia type 2

PPD/GSK GLP114179 Harmony

(A Randomized, Open-label, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of Albiglutide as Compared With Liraglutide in Subjects With Type 2 Diabetes Mellitus)

Study duration is approximately 46 weeks

Inclusion Criteria:

1. Male or female, 18 years of age or older, with a historical diagnosis of type 2 diabetes mellitus and is experiencing inadequate glycemic control on their current regimen of metformin, TZD, SU, or any combination of these oral antidiabetic medications.
2. BMI =20 kg/m2 and =45 kg/m2
3. Fasting C-peptide =0.8 ng/mL
4. HbA1c between 7.0% and 10.0%, inclusive, at Visit 5.
5. For the regular use of other medications (does not include medications excluded by the protocol), it is preferred that the subjects are receiving a stable dose for at least 4 weeks before Screening.
6. Use of oral or systemically injected glucocorticoids is generally not allowed within 3 months before randomization; short courses of oral steroids (single dose or multiple doses for up to 2 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, and topical corticosteroids are allowed.
7. Hemoglobin =10 g/dL for male subjects and =9 g/dL for female subjects
8. Creatinine clearance =11 mL/min (calculated using the Cockcroft-Gault formula)
9. Thyroid stimulating homone level is normal or clinically euthyroid as demonstrated by further thyroid tests
10. Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study including the 8-week Posttreatment Follow-up Period.
11. Able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor
12. No major illness or debility that in the investigator’s opinion prohibits the subject from actively participating in their diabetes management and completing the study
13. Able and willing to provide written informed consent

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study.

1. History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.)
2. History of treated diabetic gastroparesis
3. Current ongoing symptomatic biliary disease or history of pancreatitis
4. History of significant GI surgery, including gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper GI function
5. Recent clinically significant cardiovascular and/or cerebrovascular disease including but not limited to the following:
1. Previous history of stroke or transient ischemic attack within 1 month before Screening. Subjects who are deemed clinically stable by the investigator may be enrolled 1 month after the cerebrovascular event
2. Acute coronary syndrome, which includes the following:
• Documented MI within 2 months before Screening and during the period up until receiving the first dose of study medication
• Any cardiac surgery within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable angina not responsive to nitroglycerin within 2 months before Screening and during the period up until receiving the first dose of study medication
3. Unstable cardiac rhythm, however, as an example, controlled atrial fibrillation is allowed
4. For subjects taking a TZD, current history of heart failure (NY Heart Association Class I to IV); for subjects not taking a TZD, current history of heart failure (NY Heart Association Class II to IV)
5. Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg
6. QTc interval >470 ms confirmed by a central reader at screening.
6. Hemoglobinopathy that may affect determination of Hb A1c
7. History of human immunodeficiency virus infection
8. History of total bilirubin >1.5 x ULN unless the subject has a previously known history of Gilbert’s syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin
9. ALT or aspartate aminotransferase (AST) >2.5 x ULN3
10. Fasting triglyceride level >850 mg/dL at Screening
11. Acute symptomatic (within 3 months before Screening) infection with Hepatitis B or Hepatitis C; however subjects with past or chronic Hepatitis B or Hepatitis C are allowed provided the requirements for ALT, AST, and total bilirubin are met
12. History of a psychiatric disorder that will affect the subject’s ability to participate in the study
13. History of alcohol or substance abuse within 1 year before screening
14. Positive urine drug screen at Screening unless the subject is taking a medically approved medication for which a positive drug screen simply verifies the sue of this medication
15. Female subject is pregnant, lactating, or <six weeks postpartum
16. Known allergy to any GLP-1 analogue, liraglutide, other study medications’ excipients, excipients of albiglutide, or Baker’s yeast
17. History of type I diabetes mellitus, diabetic complications that in the opinion of the investigator would preclude effective participants in the study, or a history of ketoacidosis or hyperosmolar coma
18. Contraindications for the use of either background or potential randomized study medication
19. Receipt of any investigational drug or sitagliptin within the 30 days or 5 half-lives, whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization or receipt of albiglutide in previous studies
20. History or family history of medullary carcinoma
21. History or family history of multiple endocrine neoplasia type 2