A Randomised, Open-Label Study to Evaluate the Relative and Absolute Bioavailability of Cotadutide in Healthy Subjects
Condition: Non-alcoholic Steatohepatitis; Type 2 Diabetes Mellitus (T2DM); Chronic Kidney Disease
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      The Sponsor is developing the test medicine, cotadutide, for the potential treatment of
      non-alcoholic steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM) with chronic kidney
      disease. This healthy volunteer study will try to identify how two different concentrations
      of cotadutide are taken up by the body when dosed under the skin (subcutaneous injection).
      The study will also try to identify the absolute bioavailability of cotadutide (amount taken
      up by the body when dosed under the skin compared to an injection directly into the vein
      (intravenous)). This is a single-part, three-period study taking place at one non-NHS site in
      the UK and will involve 12 male and female (non-pregnant/non-lactating) volunteers aged
      18-55. For each study period, on Day 1 volunteers will receive cotadutide as either a
      subcutaneous injection (into the stomach) or an intravenous injection following an overnight
      fast of at least 10 hours. The subcutaneous injections will be given as either a 1 mg/ml or 5
      mg/ml concentration. The intravenous injection will be given as a 0.1 mg/ml concentration.
      Volunteers will be discharged on Day 4 and there will be a washout period of 7 days between
      dosing.

      Blood samples will be taken at regular intervals for pharmacokinetics and safety assessments
      from Day -1 to discharge. Volunteers will need to return for a follow up visit 28 (±2) days
      post-first dose for provisional of an anti-drug antibody sample and to ensure wellbeing
    

Detailed description: 
      The Sponsor is developing the test medicine, cotadutide, for the potential treatment of
      non-alcoholic steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM) with chronic kidney
      disease. NASH is a common liver disease characteristic of a damaged liver that may no longer
      work properly. T2DM is a condition that causes sugar (glucose) levels in the blood to become
      too high which can damage the blood vessels within the kidney leading to chronic kidney
      disease and also causing problems with eyes, heart and nerves. This healthy volunteer study
      will try to identify how two different concentrations of cotadutide are taken up by the body
      when dosed under the skin (subcutaneous injection). The study will also try to identify the
      absolute bioavailability of cotadutide (amount taken up by the body when dosed under the skin
      compared to an injection directly into the vein (intravenous)). The study will also assess
      the safety and tolerability of cotadutide.

      This is a single-part, three-period study taking place at one non-NHS site in the UK and will
      involve 12 male and female (non-pregnant/non-lactating) volunteers aged 18-55. For each study
      period, on Day 1 volunteers will receive cotadutide as either a subcutaneous injection (into
      the stomach) or an intravenous injection following an overnight fast of at least 10 hours.
      The subcutaneous injections will be given as either a 1 mg/ml or 5 mg/ml concentration. The
      intravenous injection will be given as a 0.1 mg/ml concentration. Volunteers will be
      discharged on Day 4 and there will be a washout period of 7 days between dosing.

      Blood samples will be taken at regular intervals for pharmacokinetics and safety assessments
      from Day -1 to discharge. Volunteers will need to return for a followup visit 28 (±2) days
      post-first dose for provisional of an anti-drug antibody sample and to ensure wellbeing
    

Intervention name(s): cotadutide solution for injection
Intervention type(s): Drug
Intervention description(s): cotadutide solution for injection
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Steatohepatitis; Diabetes; Kidney disease