erx1000 - safety, tolerability, pharmacokinetic, and pharmacodynamic study in male and female subjects with obesity

Conditions: Obesity

Summary: the primary objective is to assess the safety and tolerability of single and multiple oral doses of erx1000 in obese subjects.


Eligibility criteria:
inclusion criteria: * able to comprehend and willing to sign an informed consent form (icf) and to abide by the study restrictions. * adult females and males, of any race, between 18 and 55 years of age, inclusive, at screening. * females of non-childbearing potential, which is defined as permanently sterile (ie, due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or with bilateral tubal ligation or essure® (hysteroscopic bilateral tubal occlusion) with confirmation of occlusion of the fallopian tubes performed at least 3 months prior to screening, or postmenopausal (defined as at least 12 months post cessation of menses without an alternative medical cause and follicle-stimulating hormone \[fsh\] level ≥ 40 miu/ml). males will agree to use contraception and refrain from sperm donation. * body mass index between 30.0 and 39.9 kg/m\^2, inclusive, at screening. * glycosylated hemoglobin (hba1c) level of \< 6.5% at screening (test may be repeated once for confirmation of out-of-range values). * vital signs at screening and check-in as per the following ranges and stable (measured in a supine position after a minimum of 5 minutes of rest): 1. systolic blood pressure ≥ 90 and ≤ 140 mmhg 2. diastolic blood pressure ≥ 50 and ≤ 90 mmhg 3. pulse rate ≥ 50 and ≤ 100 bpm. * in good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ecg, vital sign measurements, and clinical laboratory evaluations at screening and/or check-in as assessed by the investigator (or designee). exclusion criteria: * any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dose administration on day 1. * significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee). * obesity induced by known endocrine or genetic disorders (eg, cushing syndrome, hypothyroidism, prader willi syndrome). * any previous surgical treatment or procedures with medical devices (such as insertion of lap band or gastric balloons) for obesity (excluding liposuction if performed \> 1 year prior to check-in). * history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, which would increase the subject's risk of participation. * history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair \> 6 months prior to screening will be allowed). * history or evidence of underlying liver disease, including viral (hepatitis b and c) or alcoholic hepatitis, or confirmed diagnosis of nonalcoholic steatohepatitis (nash); nonalcoholic fatty liver disease with qualifying liver function tests (lfts) will be allowed. * gilbert's syndrome (congenital non-hemolytic hyperbilirubinemia) or suspicion of gilbert's syndrome based on total and direct bilirubin. * laboratory results that exceed the following thresholds at screening and check-in (laboratory tests may be repeated once for confirmation of out-of-range values) as specified: 1. alanine aminotransferase (alt) \> 1.5 × upper limit of normal (uln) 2. aspartate aminotransferase (ast) \> 1.5 × uln 3. gamma glutamyl transferase (ggt), alkaline phosphatase (alp), total bilirubin, or international normalized ratio (inr) \> uln 4. hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration \< 13.0 g/dl \[130 g/l\] for males, \< 11.0 g/dl \[110 g/l\] for females) at screening or any other condition known to interfere with interpretation of hba1c measurement 5. neutrophils \< 1.5 × 109/l deemed clinically significant by investigator upon a confirmatory repeat 6. thyroid-stimulating hormone (tsh) level above the normal range, confirmed on repeat. * history or presence of cardiac arrhythmia (at the discretion of the investigator) or congenital long qt syndrome. * a qt interval corrected for heart rate using fridericia's method (qtcf) \> 450 msec for males or \> 470 msec for females on screening ecg. at the discretion of the investigator, ecg may be repeated twice and an average taken of the 3 readings. * the subject has creatinine clearance ≤ 80 ml/minute as calculated using the cockroft-gault equation. at the discretion of the investigator, evaluation may be repeated once to confirm. * history of alcoholism or drug/chemical abuse within 2 years prior to check in. * alcohol consumption of \> 14 units per week. one unit of alcohol equals 12 oz (360 ml) of beer, 1½ oz (45 ml) of liquor, or 5 oz (150 ml) of wine. * positive urine drug screen at screening; or positive alcohol breath test result or positive urine drug screen at check-in. * positive hepatitis b surface antigen and/or hepatitis c antibody and/or positive human immunodeficiency virus 1/2 (appendix 2). * participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing, whichever is longer. * subjects who are actively dieting, have gained or lost \> 5 pounds, or using or intend to use any prescription or nonprescription drugs for weight loss including herbal or other dietary supplements within 3 months prior to check-in. * use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including st. john's wort, within 30 days prior to check-in and throughout the outpatient follow-up period. * use or intend to use any prescription medications/products within 30 days prior to check-in, unless deemed acceptable by the investigator (or designee). * use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee). * use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to check-in and throughout the outpatient follow-up period, unless deemed acceptable by the investigator (or designee). * consumption of alcohol from 72 hours prior to check-in. * use of tobacco- or nicotine-containing products (including nicotine and non-nicotine e-cigarettes, vaping, etc.) within 3 months prior to check-in, or positive cotinine at screening or check-in. * receipt of blood products within 2 months prior to check-in. * donation of blood from 8 weeks prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening. * poor peripheral venous access. * have previously completed or withdrawn from this study or any other study investigating erx1000, and have previously received the investigational product. * subjects who, in the opinion of the investigator (or designee), should not participate in this study.

Keywords: erx1000 obesity