Overview

A Trial to Learn How Safe AZD9550 is in People With Type 2 Diabetes Who Are Overweight or Obese

Status:
Recruiting
Trial end date:
2025-04-04
Target enrollment:
0
Participant gender:
All
Summary
AZD9550 is in early development for the treatment of NASH, a type of liver disease that commonly affects overweight and obese patients who have T2DM. The purpose of this study is to investigate the safety, tolerability, and effects of increasing doses of AZD9550 in overweight and obese participants aged 18 through 65 years living with T2DM, and to investigate how AZD9550 is absorbed, distributed, and eliminated from the body.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AstraZeneca
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

≤75 mmol/mol (6% to 9%).

4. Body mass index from ≥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:

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:

- AST ≥ 1.5 × ULN

- ALT ≥ 1.5 × ULN

- TBL ≥ 1.5 × ULN (with the exception of Gilbert's syndrome)

- 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)

≤ 60 mL/minute/1.73m2 as defined by Chronic Kidney Disease Epidemiology Collaboration
(2021).

15. Any clinically important abnormalities in clinical chemistry, haematology,
coagulation, or urinalysis results other than those specifically described as
exclusion criteria herein, as judged by the investigator.

16. Significant late diabetic complications (macroangiopathy with symptoms of congestive
heart disease or peripheral arterial disease, microangiopathy with symptoms of
neuropathy, gastroparesis, retinopathy requiring treatment, nephropathy) detected in
laboratory results or in clinical history/documentation as judged by the investigator.

17. Abnormal vital signs, after 10 minutes of supine rest, defined as any of the
following:

- Systolic BP < 90 mmHg or ≥ 150 mmHg

- Diastolic BP < 50 mmHg or ≥ 90 mmHg

- HR < 50 or > 85 bpm at resting state

- 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 angina pectoris classified higher
than Canadian Cardiovascular Society class II or an acute coronary syndrome/acute
myocardial infarction or coronary intervention with percutaneous coronary intervention
or coronary artery bypass grafting or stroke within 6 months.

21. History of hospitalisation caused by heart failure or a diagnosis of heart failure.

22. Known or suspected history of drug abuse within the past 3 years as judged by the
investigator and /or a positive screen for drugs of abuse at screening.

23. History of severe allergy/hypersensitivity or ongoing clinically important
allergy/hypersensitivity as judged by the investigator.

24. Whole blood or red blood cell donation, or any blood loss > 500 mL (or > 400 mL in
Part D) during the 3 months prior to screening.

25. Psychiatric illness such that participants have been committed to an institution by
way of official or judicial order.

26. History of lactic acidosis or ketoacidosis.

27. Use of any of the following medicinal products:

- Use of systemic corticosteroids within 28 days prior to screening.

- Use of compounds known to prolong the QTc interval.

- Use of any herbal preparations or medicinal products licensed for control of body
weight or appetite within 3 months prior to screening.

28. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks
prior to the first administration of study intervention.

29. Received another new chemical entity (defined as a compound that has not been approved
for marketing), or has participated in any other clinical study that included drug
treatment within at least 30 days or 5 half-lives prior to the first administration of
study intervention in this study (whichever is longer). The period of exclusion to
begin 30 days or 5 halflives of IMP after the final dose, or after the last visit,
whichever is longest. Participants consented and screened, but not randomised into
this study or a previous Phase 1 study, are not excluded.

30. Previous enrolment or randomisation in the present study.

31. Concurrent participation in another study of any kind is prohibited.

32. Ongoing weight loss diet (hypocaloric diet) or use of weight loss agents, unless the
diet or treatment has been stopped at least 3 months prior to screening and the
participant has had a stable body weight (± 5%) during the 3 months prior to
screening.

33. Participants who are vegans, ones with medical dietary restrictions, or participants
who are willingly conducting any diet likely to increase ketone levels (Atkins or any
similar diet based on increased protein consummation or low carbohydrate content).

34. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea,
Coca-Cola/Pepsi or similar drink type, chocolate) as judged by the investigator.

35. Current smokers or those who have smoked or used nicotine products (including
e-cigarettes) within the previous 3 months prior to screening.

36. Participants who cannot communicate reliably with the investigator or vulnerable
participants (eg, kept in detention, protected adults under guardianship, trusteeship,
or committed to an institution by governmental or juridical order).

37. The participant is an employee, or close relative of an employee, of AstraZeneca, the
CRO, or the study site, regardless of the employee's role.

38. Judgement by the investigator that the participant should not participate in the study
if the participant is unlikely to comply with study procedures, restrictions, and
requirements.

39. Contra-indication to MRI: such as participants with pacemakers, metallic cardiac
valves, magnetic material such as surgical clips, implanted electronic infusion pumps
or other conditions that would preclude proximity to a strong magnetic field;
participants with history of extreme claustrophobia or participant cannot fit inside
the MRI scanner cavity (Parts B and C only).