A Phase I Study to Investigate the Effect of Hepatic Impairment of AZD9550 and AZD6234

Summary

The purpose of this study is to examine the safety and tolerability of AZD6234 and AZD9550 in participants with hepatic impairment and participants with normal hepatic function.

Eligibility

Inclusion Criteria

1. Age 18-85 years at consent.
2. Groups:

   * Healthy controls: Medically healthy; no clinically significant findings in history, exam, labs, vitals, or 12 lead ECG (per investigator).
   * Hepatic impairment: Chronic (≥6 months), stable; documented Child Pugh B (Group 2) or C (Group 1).
3. Stable concomitant regimen ≥2 weeks before screening (Groups 1-2).
4. T2DM allowed if HbA1c \<10% and no severe hypo/hyperglycaemia or hospitalisation within 6 months.
5. Body weight ≥50 kg; BMI 18-42 kg/m².
6. Sex assigned at birth (male/female); contraception per local regulations. Females of child bearing potential: negative pregnancy tests and condoms plus one highly effective method through 54 days post last dose. Males: condom use; no sperm donation through 54 days post last dose.
7. Written informed consent; separate consent for optional genomics.

Exclusion Criteria

Healthy controls only:

1. Any clinically significant disease; Diabetes;
2. lab values i) ALT/AST/ALP \>1.5×ULN; ii) WBC/platelets \<LLN; iii) haemoglobin \<11.0 g/dL (female) or \<12.0 g/dL (male); aPTT or PT/INR \>1.2×ULN; iv) total bilirubin \>1.5×ULN (or Gilbert's);
3. abnormal resting vital signs i) SBP \>150 or \<90 mmHg, ii) DBP \>95 or \<50 mmHg, iii) pulse ≥100 or ≤45 bpm;
4. QTcF \>450 ms or clinically significant ECG abnormalities;
5. severe allergy/hypersensitivity;
6. major surgery within 30 days;
7. pancreatitis or pancreatic enzymes \>2×ULN;
8. triglycerides \>500 mg/dL (5.6 mmol/L);
9. calcitonin \>50 ng/L (50 pg/mL);
10. severe vitamin D deficiency (\<12 ng/mL, 30 nmol/L);
11. low corrected or ionised calcium;
12. HIV positive; HBV surface/core Ab or HCV Ab positive; drug/alcohol abuse within 1 year.

    Hepatically impaired only:
13. Unstable medical/psychological conditions or uncontrolled systemic disease;
14. eGFR \<50 mL/min/1.73 m² (CKD EPI 2021);
15. Abnormal resting vital signs i) SBP \>160 or \<100 mmHg, ii) DBP \>110 or \<65 mmHg, iii) pulse ≥100 or ≤50 bpm;
16. platelets \<35×10⁹/L; neutrophils \<1.2×10⁹/L; haemoglobin \<85 g/L; HbA1c ≥10%;
17. oesophageal banding within 3 months or GI bleeding within 6 months;
18. ascites requiring paracentesis and albumin ≤4 week intervals; paracentesis within 30 days;
19. fluctuating/worsening hepatic function during screening; hepatocellular carcinoma;
20. acute liver disease due to infection/drug; hepatic impairment due to non liver disease;
21. biliary obstruction or non parenchymal causes; hepatic encephalopathy Grade ≥2;
22. functioning organ transplant or anticipated within 2 months; prior porto systemic shunt/TIPS;
23. QTcF \>480 ms or clinically significant ECG abnormalities;
24. pancreatitis or pancreatic enzymes \>2×ULN;
25. triglycerides \>500 mg/dL (5.6 mmol/L); calcitonin \>50 ng/L (50 pg/mL); severe vitamin D deficiency (\<12 ng/mL, 30 nmol/L); ionised calcium \<LLN;
26. neoplastic disease within 10 years (except adequately treated BCC/SCC or in situ cervical); MEN2 or medullary thyroid carcinoma (personal or first degree relative); significant gastric emptying abnormality;
27. HIV positive; HBV surface/core Ab or HCV Ab positive (may be included if HBV DNA or HCV RNA negative on follow up); drug/alcohol abuse within 1 year.
28. Exposure to a new chemical entity within 30 days or 5 half lives (whichever longer) before intervention; prior exposure to AZD9550 or AZD6234;

    Prior/concomitant therapy:

    Healthy controls:
29. use of prescription/non prescription/supplements within 7 days (or 14 days for enzyme inducers) or 5 half lives before intervention unless judged non interfering; current oral contraceptives or oestrogen HRT.

    Hepatically impaired:
30. prohibited-weight loss medicines (including GLP 1), agents causing significant weight gain (e.g., systemic glucocorticoids, antipsychotics), GLP 1 RAs for diabetes, QT prolonging/prokinetic agents, oral contraceptives for contraception; restricted-short systemic glucocorticoids (≤7 days), 5HT 3 antiemetics at lowest effective dose, combined oral contraceptives for non contraceptive indications. If diabetes develops and requires insulin/SU/GLP 1 RA, discontinue from study.

    Other:
31. prior enrolment in this study (screened without dosing permitted). Positive drugs of abuse and/or alcohol screen (except prescribed meds in hepatic impairment); recent blood products/donation per protocol thresholds; employees or close relatives; vulnerable populations; unlikely to comply (investigator judgement).

Conditions2

Interventions2

Locations4 sites

Browse More Trials