A Study to Understand the Safety, Tolerability, and Activity of Drug in Body Over a Period of Time of AZD2693, in Subjects of Non-Childbearing Potential in Overweight But Otherwise Healthy Subjects, and Healthy Chinese and Japanese Subjects
Condition: Metabolic Disorders; Non-alcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Overweight; Metabolic Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase 1, first-in-human (FiH), single-ascending-dose (SAD) study, will assess the safety
      and tolerability and characterize the pharmacokinetics (PK) of AZD2693, following
      subcutaneous (SC) SAD administration of AZD2693 in male and female subjects of
      non-childbearing potential in overweight but otherwise healthy subjects, and healthy Chinese
      and Japanese subjects.
    

Detailed description: 
      This is a single center study, and approximately 64 overweight/mildly obese but otherwise
      healthy male and female subjects, and up to 16 healthy Japanese subjects and 8 healthy
      Chinese (all of non-childbearing potential) will be enrolled into this study.

      Study will consist of following planned cohorts:

      Eligible healthy subjects will be divided in 6 cohorts, each consisting of 8 subjects, within
      each cohort, 6 subjects will receive AZD2693 at dose level 1 and 2 subjects will receive
      placebo. Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel
      cohort, such that 1 subject will be randomized to receive placebo and 1 subject will be
      randomized to receive AZD2693.

      Eligible healthy Japanese and Chinese subjects will be divided as two cohorts of Japanese
      subjects, and one cohort of Chinese subjects. Each cohort will consist of 8 subjects. Within
      each cohort, 6 subjects will receive AZD2693 and 2 subjects will receive placebo.

      Depending on emerging data, up to 2 additional cohorts may be added to test additional dose
      levels based on Sponsor's decision.

      Full study will comprise of following periods:

        1. Screening period of maximum 28 days.

        2. A Dosing Session during which subjects will be resident at the Clinical Unit from the
           day before investigational medicinal product (IMP) administration (Day -1) until at
           least 3 days after IMP administration with discharge on Day 4.

        3. A Follow-Up Period of 16 weeks that will consist of 9 Follow-Up Visits, for which the
           subjects will return to the Clinical Unit at 1, 2, 4, 6, 8, 10, 12, 14, and 16 weeks
           post dose.
    

Intervention name(s): AZD2693; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will receive SC injection of AZD2693 as per the arms they are randomized.; Subjects will receive SC injection of placebo matched to AZD2693, as per the arms they are randomized.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects in this study will be categorized as follows:
Overweight/mildly obese, but otherwise healthy subjects: There will be 6 cohorts, with 8 subjects in each cohort.
Japanese and Chinese subjects: There will be 2 cohorts for Japanese subjects, and one cohort for Chinese subjects, with 8 subjects in each cohort.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Single-ascending-dose; First-in-human; Chinese; Japanese; Dyslipidemia; Type II diabetes mellitus; Non-alcoholic fatty liver disease