A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People With Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated
Condition: Type II Diabetes Mellitus; Renal Insufficiency
MeSH terms: Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: MEDI0382; Placebo
Intervention description: Participants will receive subcutaneous MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.; Participants will receive SC placebo matched to MEDI0382 once daily for 32 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised, Double-Blind, Placebo-Controlled
Masking: Double (Participant, Investigator)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Maximum age: 84 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes Mellitus; MEDI0382; Renal Impairment; Glucose concentration; Hemoglobin A1c

Summary:

      A study to look at the effect MEDI0382 has on blood sugar in people with type 2 diabetes and
      kidney problems and also to check that MEDI0382 is well tolerated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 and < 85 years at screening.

          2. Signed and dated written informed consent (with the exception of consent for genetic
             and nongenetic research) prior to performing any protocol-related procedures,
             including screening evaluations.

          3. Diagnosed with type 2 diabetes mellitus (T2DM) with glucose control managed with any
             insulin and/or oral therapy combination where no significant dose changes of oral
             therapy of more than 50% have occurred in the 3 months prior to screening

          4. Body mass index (BMI) between 25 and 45 kg/m^2 (inclusive) at screening

          5. Haemoglobin A1c (HbA1c) range of 6.5 % to 10.5% (inclusive) at screening

          6. Renal impairment with estimated glomerular filtration rate (eGFR) ≥ 30 and < 60
             mL/min/1.73 m^2 at screening. Approximately 16 participants (40%) are required to have
             a screening eGFR ≥30 and < 45 mL/min/1.73 m^2 and at least 16 participants (40%) are
             required to have screening eGFR ≥45 and < 60 mL/min/1.73 m^2.

          7. Females of childbearing potential must have a negative pregnancy test at screening and
             randomisation, and must not be lactating. Women of childbearing potential who are
             sexually active with a non-sterilized male partner must be using at least one highly
             effective method of contraception from screening and up to 4 weeks after the last dose
             study drug.

        Exclusion Criteria:

          1. History or presence of significant medical or psychological conditions, including
             substance dependence/abuse, or significant abnormalities in laboratory parameters or
             vital signs including electrocardiogram (ECG), which in the opinion of the
             investigator, would compromise the participant's safety or successful participation in
             the study. As an example, severe anaemia (haemoglobin < 7.0 g/dL) could be
             exclusionary due to blood sampling required by the protocol, at the discretion of
             investigator.

          2. Concurrent participation in another interventional study of any kind and repeat
             randomisation in this study is prohibited.

          3. Any participant who has received another study drug as part of a clinical study or a
             glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30
             days or 5 half-lives of the drug (if known; whichever is longer) at the time of Visit
             2.

          4. Any participant who has received any of the following medications within the specified
             timeframe prior to the start of the study (Visit 2)

               -  Herbal preparations within 1 week prior to the start of dosing (Visit 4) or drugs
                  licensed for control of body weight or appetite (eg, orlistat,
                  bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30
                  days (or 5 half-lives of the drug) prior to the start of dosing (Visit 4)

               -  Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and
                  within the last 3 days prior to the start of the run-in period (Visit 2)

               -  Paracetamol (acetaminophen) or paracetamol-containing preparations at a total
                  daily dose of greater than 3000 mg and within the last 3 days prior to the start
                  of the run-in period (Visit 2)

               -  Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000
                  mg and within the last 3 days prior to the start of the run-in period (Visit 2)

               -  Opiates, domperidone, metoclopramide, or other drugs known to alter gastric
                  emptying and within 2 weeks prior to the start of dosing (Visit 4)

          5. Severe allergy/hypersensitivity to any of the proposed study treatments or excipients

          6. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight
             loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis

          7. Participants who have undergone a renal transplant

          8. Participants with suspicion of acute or subacute renal function deterioration (eg,
             participants with large fluctuations of creatinine values documented within the 6
             months prior to screening)

          9. Significant inflammatory bowel disease, gastroparesis, or other severe disease or
             surgery affecting the upper gastrointestinal (GI) tract including weight-reducing
             surgery and procedures) which may affect gastric emptying or could affect the
             interpretation of safety and tolerability data

         10. History of acute or chronic pancreatitis

         11. Significant hepatic disease (except for non-alcoholic steatohepatitis or nonalcoholic
             fatty liver disease without portal hypertension or cirrhosis) and/or participants with
             any of the following results:

               -  Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)

               -  Alanine transaminase (ALT) ≥ 3 × ULN

               -  Total bilirubin ≥ 2 × ULN

         12. Poorly controlled hypertension defined as:

               -  Systolic blood pressure (BP) > 180 mm Hg

               -  Diastolic BP ≥ 100 mm Hg Participants who fail BP screening criteria may be
                  considered for 24-hour ambulatory blood pressure monitoring (ABPM) at the
                  discretion of the investigator. Participants who maintain a mean 24-hour systolic
                  BP ≤ 180 or diastolic BP < 100 mm Hg with a preserved nocturnal dip of > 15% will
                  be considered eligible

         13. Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke
             within 3 months prior to screening, or participants who have undergone percutaneous
             coronary intervention or a coronary artery bypass graft within the past 6 months or
             who are due to undergo these procedures at the time of screening

         14. Severe congestive heart failure (New York Heart Association Class III or IV)

         15. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary
             thyroid carcinoma or multiple endocrine neoplasia

         16. History of neoplastic disease within 5 years prior to screening, except for adequately
             treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer

         17. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C
             antibody, and human immunodeficiency virus (HIV) antibody

         18. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (ACR) > 250
             mg/mmol at screening

         19. History of substance dependence, alcohol abuse, or excessive alcohol intake (defined
             as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks
             for women) within 3 years prior to screening, and/or a positive screen for drugs of
             abuse or alcohol at screening or on Day -5. Participants who use tricyclic
             antidepressants or benzodiazepines for an established clinical indication may be
             permitted to enter the study based upon the judgement of the investigator