The Effect of Betahistine on Body Weight in Obese Subjects

Inclusion Criteria:

• Signed written informed consent;
• Male or female subjects 18 to 65 years of age;
• Is obese with a BMI greater than or equal to 30 kg/m2 to less than or equal to 40 kg/m2;
• Has been obese for at least 1 year prior to screening; and
• If female, is nonlactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to randomization or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year) must practice or be willing to continue to practice appropriate birth control (such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire study duration.

Exclusion Criteria:

• Has obesity of known endocrine origin (e.g., Cushing's disease, Addison's disease, hypothalamic tumor);
• Has a medical history (e.g., morbid childhood obesity) and/or physical characteristics (e.g., polydactyly) suggestive of genetic obesity (e.g., ob/ob genotype) or syndromatic obesity (e.g., Prader-Willi syndrome, Bardet Biedl syndrome);
• Previous surgical procedures for weight loss;
• Has had liposuction within 1 year before screening or is planning to have liposuction during the study;
• History of bulimia or evidence of laxative abuse;
• Has had a body weight loss of >4 kg in the 90 days prior to screening;
• Has taken drugs capable of influencing body weight 30 days prior to screening;
• Has recently started or plans on starting a smoking cessation program;
• Has had a major change in daily physical activity (e.g., initiation of an exercise program) or started a weight loss program within 90 days prior to screening;
• Is unwilling or unable to participate in a dietary program as part of the study;
• Is <80% compliant with study medication in the single-blind placebo run-in period;
• Has a clinically significant history or presence of any of the following conditions:
• Active or past history of cardiovascular or cerebrovascular disease including unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, congestive heart failure, or cardiac valve abnormalities;
• Liver disease (irrespective of transaminase concentrations);
• Pheochromocytoma;
• Porphyria;
• Type 1 diabetes mellitus;
• Type 2 diabetes mellitus on treatment other than metformin monotherapy and/or diet with HbA1c less than or equal to 8%;
• Severe type 2 diabetes with history of ketoacidosis or diabetic ulcers, or presence of retinopathy, neuropathy, or nephropathy;
• Renal insufficiency defined as a serum creatinine greater than or equal to 1.5 mg/dL (133 µmol/L) at screening;
• Malignant disease within 5 years of screening;
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x ULN;
• Thyroid-stimulating hormone (TSH) outside of the normal range;
• Plans on having any surgery (elective or otherwise) during the course of the study;
• Has uncontrolled hypertension (sitting blood pressure >160/95 mmHg at screening or randomization), uncontrolled hyperlipidemia (triglycerides [TG] greater than or equal to 400 mg/dL or low-density lipoprotein cholesterol [LDL-C] >160 mg/dL), or uncontrolled diabetes (HbA1c >8%);
• History of asthma;
• History of peptic ulcers;
• History of HIV;
• History of undiagnosed allergy, severe allergy, or drug allergy, including history of anaphylaxis, angioedema, bronchospasm, or urticaria;
• Has clinical laboratory test values (chemistry, hematology, or urinalysis) judged to be clinically significant by the investigator;
• Has a physical examination or electrocardiogram (ECG) with significant abnormalities, as judged by the investigator;
• Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion could cause the subject to be noncompliant with study procedures;
• Has hypersensitivity to betahistine;
• Has psychiatric or neurological disorders requiring chronic medications (e.g., antidepressants), subjects are to be unlikely to have a major depressive episode (score of lees than or equal to 8) on The Harvard Department of Psychiatry and National Depression Screening Day Scale (THE HANDS) (See Appendix E);
• Chronic or as needed use of antihistamines;
• Has not been on a stable treatment regimen with any of the following medications for a minimum of 90 days prior to screening:
• Hormone replacement therapy;
• Oral contraceptives;
• Antihypertensive agents;
• Metformin;
• Lipid-lowering agents; or
• Thyroid replacement therapy;
• Has been treated over the past 60 days, is currently treated, or is expected to require or undergo treatment with any of the following excluded medications;
• All prescription or over-the-counter agents taken for the purpose of weight reduction, including (but not limited to) the following anti obesity agents:
• Prescription drugs such as orlistat (Xenical), sibutramine (Meridia), and phentermine (Adipex-P, Celltech, Pro-Fast SA, Pro-Fast SR, Fastin, Oby trim, Zantryl, Teramine, Phentride, Phentercot, Obephen, Oby-cap); or
• Over-the-counter antiobesity agents (e.g., herbal supplements or other alternative remedies such as Cortislim, Dexatrim, Acutrim);
• Psychotropic/neurological agents including the following:
• Antipsychotic agents (e.g., olanzapine, clozapine, risperidol, lithium, etc.).
• Antiepileptic agents (e.g., Topamax®, Zonegran®, valproate, carbamazepine); or
• Antidepressant agents including the following: monoamine oxidase inhibitors, bupropion (Wellbutrin®, Zyban®), tricyclic antidepressants, and tetracyclic antidepressants; and selective serotonin reuptake inhibitors (e.g., Prozac®, Paxil®, Zoloft®, etc.);
• Systemic steroids administered by oral, intravenous, or intramuscular route;
• Drugs that directly affect gastrointestinal motility (e.g., Reglan® and Propulsid®, and chronic [taken for more than 10 days within a 6-month period] macrolide antibiotics such as erythromycin and newer derivatives);
• Calcitonin (e.g., Miacalcin®);
• Insulin;
• Exenatide (Byetta®);
• Sulfonylureas (e.g., Diamicron®, Amaryl®, Glucotrol®, Micronase®); or Meglitinides (e.g., Starlix®, Prandin®)
• Has received any investigational drug within 90 days of screening;
• Receipt of any investigational treatment (drug or device) within 90 days prior to screening;
• Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or
• Is employed by OBEcure Ltd.