Non-alcoholic Steatohepatitis (NASH)
Conditions
Interventions
Parts C and D: Bi-weekly/monthly up-titration (starting at 0.3 mg titrating up to 9.4 mg, if
tolerated) of AZD9550/placebo for 24 weeks in overweight/obese participants with
T2DM (Part C) and in overw
Sponsors
Kinumura Takumi
Eligibility
Inclusion criteria
Inclusion criteria: 1. Males or females of non-childbearing potential age 18 through 65 years at the time of screening. 2. Parts A, B, C only: Participants with a diagnosis of T2DM and glucose control managed with diabetes diet and in addition to metformin treatment no more than two treatment options (with a stable dose 3 months prior to screening). Part D only: Participants who are diagnosed with T2DM, have inadequate glycaemic control with diet and exercise. Participants who are prescribed an oral anti-diabetic agent such as metformin, a DPP IV inhibitor, sulphonylurea, glinides, alphaglucosidase inhibitors, and an SGLT2 inhibitor may be eligible to enter the study following a washout of 4-weeks or 5-half lives (whichever is longer) washout period. 3. Participants with a screening HbA1c value within the target range of >_42 to _27 (>_25 in Part D) to <_39.9 kg/m2 (inclusive). 5. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 6. Written informed consent and any locally required authorization (eg, European Union Data Privacy Directive) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations 7. Ability to complete and meet all eligibility requirements for randomisation within 60 days after signing the ICF. 8. Venous access suitable for multiple cannulations. 9. Willing and able to self-administer weekly SC injections (Parts C and D only).
Exclusion criteria
Exclusion criteria: 1. Participants with T2DM treated with insulin. 2. Participants with T2DM treated with more than 3 anti-diabetic therapies. 3. Participants with T2DM treated with a GLP-1RA within 3 months of screening. 4. History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. 5. Serum calcitonin suggestive of thyroid C-cell hyperplasia (calcitonin level > 50 ng/L), medullary thyroid carcinoma, or history or family history of multiple endocrine neoplasia at screening. 6. History or presence of GI, renal, or hepatic disease (with the exception of Gilbert's syndrome), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs, as judged by the investigator. 7. History of cancer within the last 10 years, with the exception of non-melanoma skin cancer. 8. Any clinically important illness (apart from T2DM), as judged by the investigator. 9. Any medical/surgical procedure, or trauma within 4 weeks prior to screening, at the discretion of the investigator. 10. Symptoms of insulinopenia or poor blood glucose control (eg, significant thirst, nocturia, polyuria, polydipsia, or weight loss). 11. Positive hepatitis B or hepatitis C virus serology at screening. 12. Positive human immunodeficiency virus test at screening or participant taking antiretroviral medications as determined by medical history or participant's verbal report. 13. At screening blood tests, any of the following: o AST >_ 1.5 x ULN o ALT >_ 1.5 x ULN o TBL >_ 1.5 x ULN (with the exception of Gilbert's syndrome) o Haemoglobin below the lower limit of the normal range or any other clinically significant haematological abnormality as judged by the investigator. 14. Impaired renal function defined as estimated glomerular filtration rate (eGFR) _ 150 mmHg o Diastolic BP _ 90 mmHg o HR 85 bpm at resting state o Participants may be re-tested for the vital signs criteria only once if, in the investigator's judgement, they are not representative of the participant. 18. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, as considered by the investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy. 19. Participants with implantable cardiac defibrillator or a permanent pacemaker, and participants with symptomatic tachy- or brady-arrhythmias. 20. Participants with unstable angina pectoris or stable angi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part D - Principal aim is to evaluate the safety, tolerability, PK, and PD of repeat escalating doses of AZD9550 up to the MTD in participants of Japanese descent | — |
Countries
Austria, Germany, Japan, Sweden
Contacts
Public ContactTakumi Kinumura
Fortrea Japan K.K.
Outcome results
None listed