The Effect of Betahistine on Body Weight in Obese Subjects

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Examine the Effect of Betahistine on Body Weight in Obese Subjects

The purpose of this study is to examine the effect that betahistine has 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, sibutramine, and phentermine; 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.