A First-in-Human, Phase 1, Open-Label, Crossover Study Evaluating the Effect of Food on the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of EBMC-710GO in Healthy Adults who are Overweight or have Obesity

Exclusion Criteria46

• Known hypersensitivity to the study drug or any of the study drug ingredients.
• History of anaphylaxis or other significant allergy (i.e., multiple food or drug allergies) which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
• History or presence of CS cardiovascular (including active hypertension and/or history of poor or uncontrolled hypertension), pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
• History or current diagnosis with type 1 or type 2 diabetes mellitus.
• History or presence of clinically relevant oesophageal or gastrointestinal disease/disorders, including (but not limited to) cholecystectomy, pancreatitis, irritable bowel syndrome, and inflammatory bowel disease. Note: A history of gastroesophageal reflux disease is not exclusionary.
• History of hypo/hyperthyroidism (except those undergoing replacement with thyroxine and on a stable dose for the at least 2 months at the time of screening), repeated thyroid stimulating hormone (TSH) values that are abnormal at screening, or obesity of endocrine origin.
• Presence or sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (e.g., over or under production of clinical or laboratory assessments).
• Any CS (as determined by PI [or delegate]) disorders of skin and hair follicle pigmentation (including but not limited to albinism and vitiligo), and CS dermatological conditions (e.g., eczema).
• A CS acute illness within 1 week prior to dosing.
• History of surgical treatment for obesity or any other major gastrointestinal surgery (as determined by the PI [or delegate]).
• History of surgery or hospitalisation within 6 months prior to screening, or surgery planned during the study. If a previous surgical procedure was performed within 6 months and a full recovery was made with no expected impact on study procedures or participant safety, the participant may be eligible at the discretion of the PI and Medical Monitor.
• Any history of malignant disease in the last 10 years except for fully resolved surgically resected skin squamous or basal cell carcinoma or cervical intraepithelial neoplasia.
• History of cardiac abnormalities, including a family history of long QT syndrome and/or family history of sudden death in an otherwise healthy individual between the ages of 1 and 30 years.
• Abnormal and clinically relevant ECG characteristics at Screening including, but not limited to:
• a. bradycardia or tachycardia (sinus rate 100 bpm)
• b. complete left bundle branch block
• c. complete right bundle branch block
• d. second- or third-degree heart block
• e. intraventricular conduction delay with QRS duration >120 ms, QTcF duration >450 msec (males) or >470 msec (females)
• f. pathological Q-wave
• g. symptomatic or asymptomatic arrhythmias (excluding sinus arrhythmia)
• h. evidence of ventricular pre-excitation
• i. frequent palpitations or syncopal episodes
• j. heart failure (i.e., all stages of diagnosed heart failure)
• Any CS neurological or psychiatric diagnosis or psychological or behavioural problems (e.g., major depression, anxiety, suicidal behaviour or attempts, or other psychiatric disorder) that, in the opinion of the investigator, would interfere with the participant’s ability to participate in the study.
• Any suicidal ideation with intent, with or without a plan, within 2 years before screening or during screening (i.e., answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS).
• Presence of clinically relevant immunosuppression including, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase, bilirubin (total, conjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT or AST above the limits specified may be included, at the discretion of the PI (or delegate), if unaccompanied by clinical signs and are determined to be normal variants.
• Serum creatinine above the ULN.
• Fibrinogen above the ULN.
• A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
• History of alcohol or illicit drug abuse.
• Positive drugs of abuse test, cotinine test, or alcohol breath test results at the screening visit and/or on admission to the study site on Day 1.
• Regular consumption of more than 14 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], or 30 mL spirit [40% Alc/Vol]), and/or the volunteer is unwilling to abstain from alcohol for at least 24 hours prior to check-in to the study site, while confined to the study site, and for at least 24 hours prior to an outpatient appointment.
• Volunteer smokes more than 5 cigarettes or equivalent nicotine-containing products per week, and/or the volunteer is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in to the study site, throughout the confinement period(s) at the study site, for the duration of the treatment period, and for 72 hours prior to each outpatient appointment.
• Note: 1 average cigar is equal to approx. 5 average cigarettes; 1 average pipe session is equal to approx. 5 average cigarettes; 1 average nicotine liquid vape session is equal to 1 average e-cigarette or 1 average cigarette.
• A heavy caffeine drinker (consume equivalent of >5 cups or glasses of caffeinated beverages [e.g., coffee, tea, cola, energy drink] per day), and/or the volunteer is unwilling to abstain from the consumption of caffeine and/or xanthene products for at least 24 hours prior to check-in to the study site, while confined to the study site, and for at least 24 hours prior to an outpatient appointment.
• Females who are breastfeeding or planning to breastfeed.
• Unable to swallow oral medication.
• Use of weight-lowering pharmacotherapy (including dietary aids or supplements), or dieting and organised weight loss program within 3 months prior to screening. Note: Regular physical exercise is permitted upon consultation with the PI.
• Use of any prescription or over-the-counter medication (including herbal products, vitamins, hormone supplements, homeopathic preparations, cannabinoids) within 14 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of IP. The following are permitted: use of contraceptives, use of paracetamol (up to 2 g per day) for no more than 3 consecutive days, use of ibuprofen (up to 600 mg per day) for no more than 3 consecutive days, and use of medications for gastroesophageal reflux disease (e.g., H2 blockers or proton pump inhibitors) except for 24 hours prior to IP administration.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic, or antiviral medication within 10 days prior to first dose of IP.
• Received vaccination(s) within 14 days prior to dosing or has vaccination(s) planned during the study.
• Donation of blood or plasma within 90 days prior to first dose of the study drug, or loss of whole blood of more than 500 mL within 90 days prior to first dose of the study drug, or receipt of a blood transfusion within 1 year of the first dose of the study drug.
• Participation in another clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening. Note: Participants may only participate once (i.e., in one cohort) in the current study.
• Any other condition or prior therapy that in the opinion of the PI (or delegate) would pose a risk or make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.