A First in Human Study to Evaluate the Safety, Tolerability and PK of GB1211 in Healthy Subjects

Inclusion Criteria

Subjects for Parts A and B must satisfy all of the following criteria at the Screening visit unless otherwise stated:

• Males or females, of any race, between 18 and 55 years of age (60 years for Part B), inclusive.
• Body mass index (BMI) of 18.0 to 32.0 kg/m^2 (inclusive) with a minimum body weight of 50 kg.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed further in the protocol.
• Male subjects must agree to refrain from sperm donation and females should refrain from ova donation from the date of Check-in (Day -1) until 90 days after the Follow-up visit.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Subjects for Parts C must satisfy all of the following criteria at the Screening visit unless otherwise stated:

• Males or females, of any race, between 18 and 60 years of age, inclusive.
• Body mass index (BMI) of ≥ 25.0 and ≤ 38.0 kg/m^2.
• Documented history of fatty liver within the last 24 weeks by one of the following: magnetic resonance imaging (MRI) suggesting liver fat ≥ 8%, ultrasound (US) indicating fatty liver, or Fibroscan Controlled Attenuation Parameter (CAP) > 270 dB/m. In subjects without a documented history of fatty liver, a Fibroscan CAP or US can be performed at Screening. Subjects with Fibroscan CAP > 270 dB/m or US indicating fatty liver are eligible.
• Metabolic syndrome (Adult Treatment Panel III definition) or T2DM (defined as stable diabetes with glycosylated haemoglobin [HbA1c] ≤ 9.5%).
• Alanine aminotransferase (ALT) ≥ 20 U/L for females and ≥ 30 U/L for males at Screening.
• Fibroscan ≥ 7 KPa and 450 msec confirmed by repeat measurement. b. QRS duration > 110 msec confirmed by repeat measurement. c. PR interval > 220 msec confirmed by repeat measurement. d. findings which would make QTc measurements difficult or QTc data uninterpretable. e. history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).

3 (Part B). Clinically significant ECG abnormalities or QTcF greater than 450 msec for males and 470 msec for females at either Screening or Day 1 predose, or any prior history of QT abnormality.

• History of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
• Positive hepatitis panel and/or positive human immunodeficiency virus (HIV) test.
• Participation in a clinical study involving administration of an investigational agent or vaccine (new chemical entity) or having received a biological product in the past 90 days prior to dosing.
• 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 dosing, unless deemed acceptable by the Investigator (or designee).
• Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
• Use of tobacco- or nicotine-containing products 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 and donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• Subject who, in the opinion of the Investigator (or designee), should not participate in this study.

Subjects from Part C will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated:

• If diabetic and diabetes is other than T2DM