A Phase I/II, Randomised, Single-blind, Placebo-controlled, Multiple-ascending-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD9550 Monotherapy and Co-administration of AZD9550 and AZD6234 in Participants Living With Obesity and Overweight With or Without Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 166
- 试验地点
- 16
- 主要终点
- Area Under Concentration-Time Curve of AZD9550 following repeat weekly SC doses
研究概览
简要总结
AZD9550, previously being developed for the treatment NASH, is a dual GCG and GLP-1 receptor agonist. AZD9550 is now being developed in combination with AZD6234, a SARA, for the treatment of overweight and obesity and its associated co-morbidities. Co-administration of AZD9550 and AZD6234 is currently being evaluated in participants living with obesity and overweight without T2DM in an ongoing Phase 2b study.
The purpose of this study is to investigate the safety, tolerability, and effects of increasing doses of AZD9550 monotherapy in overweight and obese participants aged 18 through 65 years living with or without T2DM, and to investigate how AZD9550 is absorbed, distributed, and eliminated from the body (Parts A-D).
In addition, the study will investigate the safety and tolerability of co-administration of AZD9550 and AZD6234 in participants living with T2DM with obesity or overweight aged 18 through 75 years (Part E), and safety and tolerability for different titration regimens for AZD9550 in participants living with obesity, but without T2DM, aged 18 through 75 years (Part F).
详细描述
This Phase I/II, randomised, single-blind, placebo-controlled, MAD study will assess the safety and tolerability of AZD9550 monotherapy and co-administration of AZD9550 and AZD6234 and will characterise the PK and PD of AZD9550 monotherapy and co-administration of AZD9550 and AZD6234 following SC administration to overweight and obese participants living with or without T2DM. Inclusion of participants receiving placebo is appropriate for benchmarking the safety and tolerability of AZD9550 and co-administration of AZD9550 and AZD6234. A randomised and single-blind study design has been chosen to minimise bias and includes a placebo to facilitate identification of effects related to the administration of the study intervention rather than the study procedures or situation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This study is single-blind with regard to treatment (AZD9550 monotherapy, co-administered AZD9550 and AZD6234, or placebo). This means that the participant, investigator, Study Monitor, and the clinical unit staff will remain blinded during each part of the study and the randomisation code will only be available at each predefined decision point before the SRC meeting in order to review the data unblinded, if necessary. The sponsor will be unblinded throughout the study.
AZD9550, AZD6234, and placebos will as far as possible be matched for appearance and volume. Participants randomised to placebo will receive the same volume of injection (SC cohorts) as participants on active treatment. In Part E, the number of injections per dosing occasion (ie, 2) will be the same in all treatment arms.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged 18 through 65 years (Parts A-D) or 75 years (Part E-F) at the time of screening.
- •Parts A, B, C only: Participants with or without T2DM. If participants have a diagnosis of T2DM, the 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.
- •Part E only: Participants are eligible to be included in the Part E only if they meet all of the following criteria at screening:
- •Diagnosed with T2DM.
- •Are treated with diet and exercise only, or any combination of OAD with stable doses in the 3 months prior to dosing.
- •Participants prescribed a DPP IV inhibitor or a GLP-1RA-containing medicine, alone or in combination with other OADs, may be eligible to enter the study if they have not been treated with any of these drugs for at least 35 days or 5 drug half-lives (whichever is longer) prior to randomisation.
- •Participants with a screening HbA1c value within the target range of
- •Parts A to E:≥ 42 to ≤ 86 mmol/mol (6% to 10%).
- •Part F: < 48 mmol/mol (6.5%).
- •Body mass index from ≥ 27 to ≤ 39.9 kg/m2 (inclusive) (Part A-C) or ≥ 27 kg/m2 (Part E), or ≥ 30 kg/m2 (Part F).
- •Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •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
- •Ability to complete and meet all eligibility requirements for randomisation within 60 days after signing the ICF.
- •Venous access suitable for multiple cannulations.
- •Willing and able to "route of administration" weekly SC injections (Parts C, D, E, and F only).
排除标准
- •Participants with T2DM (Part F) and participants with T2DM treated with insulin (Parts A-E).
- •Participants with T2DM treated with more than 3 anti-diabetic therapies (Parts A-D only).
- •Treatment with GLP-1RA or GLP-1RA/GIPRA within 3 months of screening (Parts A to C only) or within 35 days of randomisation or five half-lives (whichever is shorter) of dosing (Parts E and F only).
- •History of any clinically important disease or disorder which 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.
- •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.
- •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.
- •History of cancer within the last 10 years, with the exception of non-melanoma skin cancer.
- •Any clinically important illness (apart from T2DM), as judged by the investigator.
- •Any medical/surgical procedure, or trauma within 4 weeks prior to screening, at the discretion of the investigator.
- •Symptoms of insulinopenia or poor blood glucose control (eg, significant thirst, nocturia, polyuria, polydipsia, or weight loss).
- •Positive hepatitis B or hepatitis C virus serology at screening.
- •Positive human immunodeficiency virus test at screening or participant taking antiretroviral medications as determined by medical history or participant's verbal report.
- •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.
- •Total serum calcium, albumin-corrected calcium or ionised calcium < LLN at screening (Part E).
- •Impaired renal function defined as eGFR ≤ 60 mL/minute/1.73 m2 as defined by Chronic Kidney Disease Epidemiology Collaboration (2021) (Part A to C); or ≤ 45 mL/minute/1.73 m2 (Parts E and F).
- •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.
- •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.
- •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.
- •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.
- •Participants with implantable cardiac defibrillator or a permanent pacemaker, and participants with symptomatic tachy- or brady-arrhythmias.
- •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.
- •In Parts A-D: History of hospitalisation caused by heart failure or a diagnosis of heart failure. In Part E, severe congestive heart failure (New York Heart Association Class III or IV) or recent (< 6 months) hospitalisation due to heart failure.
- •Known or suspected history of drug abuse within the past 3 years as judged by the investigator (Parts A-F) and/or a positive screen for drugs of abuse at screening (Parts A-C only).
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
- •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.
- •History of psychosis or bipolar disorder.
- •History of major depressive disorder within the 2 years prior to screening or depression, where the participant is deemed to be clinically unstable as judged by the investigator.
- •Previous hospitalisation for any psychiatric reason.
- •Questionnaire score ≥ xx within the x years prior to screening or at screening (Parts E and F only).
- •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.
- •History of lactic acidosis
- •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.
- •Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of study intervention.
- •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 half-lives 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 previous AZD9550, AZD6234, or AZD9550/AZD6234 combination studies, are not excluded from Part E.
- •Previous enrolment or randomisation in the present study.
- •Concurrent participation in another study of any kind is prohibited.
- •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.
- •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) (Part A-D only).
- •Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, Coca-Cola/Pepsi or similar drink type, chocolate) as judged by the investigator (Part A-D only).
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研究组 & 干预措施
Part B: AZD9550
Once weekly up-titration over 5 doses of AZD9550 in overweight/obese participants with or without T2DM
干预措施: AZD9550 (Drug)
Part C: AZD9550
Bi-weekly/monthly up-titration of AZD9550 for 24 weeks in overweight/obese participants with or without T2DM.
干预措施: AZD9550 (Drug)
Part A: placebo
Multiple repeat doses of placebo given as 4 once weekly SC doses for 4 weeks to 2 sequential cohorts in overweight/obese participants with or without T2DM, evaluating 2 low dose levels of AZD9550
干预措施: placebo (Drug)
Part B: placebo
Once weekly administration of placebo over 5 doses, volume matched to the active treatment being up-titrated, in overweight/obese participants with or without T2DM
干预措施: placebo (Drug)
Part C: placebo
Bi-weekly/monthly administration of placebo - volume matched to the active treatment being up-titrated - for 24 weeks in overweight/obese participants with or without T2DM.
干预措施: placebo (Drug)
Part F: AZD9550
Bi-weekly/monthly up-titration of AZD9550 for 28 weeks in obese participants without T2DM.
干预措施: AZD9550 (Drug)
Part D: placebo
Bi-weekly/monthly administration of placebo - volume matched to the active treatment being up-titrated - 24 weeks in overweight/obese Japanese participants with T2DM.
干预措施: placebo (Drug)
Part E: placebo
Bi-weekly/monthly administration of placebo - volume matched to the active treatments being up-titrated - 24 weeks in overweight/obese participants with T2DM.
干预措施: placebo (Drug)
Part E: AZD9550 and AZD6234
Bi-weekly/monthly up-titration of AZD9550 and AZD6234 for 24 weeks in overweight/obese participants with T2DM.
干预措施: AZD9550 and AZD6234 (Drug)
Part F: placebo
Bi-weekly/monthly administration of placebo - volume matched to the active treatment - 28 weeks in obese participants without T2DM.
干预措施: placebo (Drug)
Part A: AZD9550
Multiple repeat doses of AZD9550 given as 4 once weekly SC doses for 4 weeks to 2 sequential cohorts in overweight/obese participants with or without T2DM, evaluating 2 low dose levels of AZD9550
干预措施: AZD9550 (Drug)
Part D: AZD9550
Bi-weekly/monthly up-titration of AZD9550 for 24 weeks in overweight/obese Japanese participants with T2DM.
干预措施: AZD9550 (Drug)
结局指标
主要结局
Area Under Concentration-Time Curve of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
* AUC from 0 to the time of the last measured concentration (AUClast) at first dose and last dose * AUC over a dosing interval (AUCtau) at first dose and last dose. Applicable for Part A.
Maximum observed concentration of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Cmax at first dose and last dose Applicable for Part A.
Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• t1/2λz at first dose and last dose Applicable for Part A.
Time to maximum observed concentration of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• tmax at first dose and last dose Applicable for Part A.
Apparent oral clearance of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• CL/F at first dose and last dose Applicable for Part A.
Apparent volume of distribution of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Vz/F at first dose and last dose Applicable for Part A.
Ratio for AUC of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Rac AUCtau at last dose Applicable for Part A.
Ratio for Cmax of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Rac Cmax at last dose Applicable for Part A.
Number and percentage of participants with any AE, SAEs, AEs leading to discontinuation of study intervention, AEs with outcome of death, and AEs leading to withdrawal from study.
时间窗: Day - 35 to Day 205
Applicable for Parts A, B, C, D, E.
Number and percentage of participants with clinically significant changes from baseline in Vital Sign Parameters.
时间窗: Day - 35 to Day 205
Applicable for Parts A, B, C, D, E.
Area Under Concentration-Time Curve of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
* AUC from 0 to the time of the last measured concentration (AUClast) at first dose and last dose * AUC over a dosing interval (AUCtau) at first dose and last dose. Applicable for Part A.
Number and percentage of participants with clinically significant changes in ECG parameters.
时间窗: Day - 35 to Day 205
Applicable for Parts A, B, C, D, E.
Number and percentage of participants with clinically significant changes from baseline in Clinical Laboratory Parameters
时间窗: Day - 35 to Day 205
Applicable for Parts A, B, C, D, E.
Maximum observed concentration of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Cmax at first dose and last dose Applicable for Part A.
Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• t1/2λz at first dose and last dose Applicable for Part A.
Time to maximum observed concentration of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• tmax at first dose and last dose Applicable for Part A.
Apparent oral clearance of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• CL/F at first dose and last dose Applicable for Part A.
Apparent volume of distribution of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Vz/F at first dose and last dose Applicable for Part A.
Ratio for AUC of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Rac AUCtau at last dose Applicable for Part A.
Ratio for Cmax of AZD9550 following repeat weekly SC doses
时间窗: Day 1 to Day 65
• Rac Cmax at last dose Applicable for Part A.
次要结局
- PD effect of AZD9550 on fasting glucose compared to placebo(From baseline to Week 24)
- Absolute and percentage change in body weight from baseline(From baseline to Week 4)
- Incidence of anti-AZD9550 antibodies(Day 1 to Day 205)
- Absolute change in percentage body fat from baseline(From baseline to Week 4)
- Effect of AZD9550 on hepatic fat fraction versus placebo at Week 5(From baseline to Week 5)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 24 hours(From baseline to Day 176)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 7 days(From baseline to Day 176 and during 14 days post last dose)
- Percentage change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Percentage change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Change in liver volume as measured by MRI(From baseline to Week 5)
- Absolute change in body weight(From baseline to Week 5)
- Percent change in body weight(From baseline to Week 5)
- Proportion of participants achieving ≥ 5% body weight loss(From baseline to Week 5)
- Proportion of participants achieving ≥ 10% body weight loss(From baseline to Week 5)
- Change in liver volume, visceral and SC fat as measured by MRI(From baseline to Weeks 13 and 24)
- Anti-AZD9550 antibody titre among participants with positive serum antibodies to AZD9550(Day 1 to Day 205)
- Maximum observed concentration of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Time to maximum observed concentration of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Apparent oral clearance of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Apparent volume of distribution of AZD9550 following repeat weekly SC doses(Day 1 to day 169)
- Change in visceral and subcutaneous fat as measured by MRI(From baseline to week 5)
- PD effect of AZD9550 on glucose metabolism compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on fasting insulin compared to placebo(From baseline to Week 5)
- PD effect of AZD9550 on fasting c-peptide compared to placebo(From baseline to Week 5)
- Absolute change in percentage body fat(From baseline to Week 5)
- PD effect of AZD9550 on HbA1c compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on glucose metabolism following an MMTT compared to placebo(From baseline to Week 13 and Week 24)
- Area Under concentration-time Curve of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- The effect of AZD9550 on hepatic fat fraction versus placebo after 13 and 24 weeks of treatment(From baseline to Weeks 13 and 24)
- Effects of AZD9550 compared to placebo on body weight(From baseline to Week 24)
- Change in daily (24 hours) average glucose levels as measured by CGM(From baseline to Weeks 1, 2, 3, 4, 5, and 6, and during 14 days post last dose)
- Change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Week 5)
- Change in 7-day average glucose levels as measured by CGM(From baseline to Day 176)
- Change in coefficient of variation of glucose levels as measured by CGM over 7 days(From baseline to Day 176 and during 14 days post last dose)
- PD effect of AZD9550 on fasting glucose compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on fasting lipid profile compared to placebo(From baseline to Week 24)
- Absolute and percentage change in body weight from baseline(From baseline to Week 4)
- Incidence of anti-AZD9550 antibodies(Day 1 to Day 205)
- Absolute change in percentage body fat from baseline(From baseline to Week 4)
- Effect of AZD9550 on hepatic fat fraction versus placebo at Week 5(From baseline to Week 5)
- PD effect of AZD9550 on glucose metabolism following an MMTT compared to placebo(From baseline to Week 13 and Week 24)
- Area Under concentration-time Curve of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- The effect of AZD9550 on hepatic fat fraction versus placebo after 13 and 24 weeks of treatment(From baseline to Weeks 13 and 24)
- Effects of AZD9550 compared to placebo on body weight(From baseline to Week 24)
- Change in daily (24 hours) average glucose levels as measured by CGM(From baseline to Weeks 1, 2, 3, 4, 5, and 6, and during 14 days post last dose)
- Change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Week 5)
- Change in 7-day average glucose levels as measured by CGM(From baseline to Day 176)
- Change in coefficient of variation of glucose levels as measured by CGM over 7 days(From baseline to Day 176 and during 14 days post last dose)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 24 hours(From baseline to Day 176)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 7 days(From baseline to Day 176 and during 14 days post last dose)
- Percentage change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Percentage change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Change in liver volume as measured by MRI(From baseline to Week 5)
- Absolute change in body weight(From baseline to Week 5)
- Percent change in body weight(From baseline to Week 5)
- Proportion of participants achieving ≥ 5% body weight loss(From baseline to Week 5)
- Proportion of participants achieving ≥ 10% body weight loss(From baseline to Week 5)
- Change in liver volume, visceral and SC fat as measured by MRI(From baseline to Weeks 13 and 24)
- Anti-AZD9550 antibody titre among participants with positive serum antibodies to AZD9550(Day 1 to Day 205)
- Maximum observed concentration of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Time to maximum observed concentration of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Apparent oral clearance of AZD9550 following repeat weekly SC doses(Day 1 to Day 169)
- Apparent volume of distribution of AZD9550 following repeat weekly SC doses(Day 1 to day 169)
- Change in visceral and subcutaneous fat as measured by MRI(From baseline to week 5)
- PD effect of AZD9550 on glucose metabolism compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on fasting insulin compared to placebo(From baseline to Week 5)
- PD effect of AZD9550 on fasting c-peptide compared to placebo(From baseline to Week 5)
- Absolute change in percentage body fat(From baseline to Week 5)
- PD effect of AZD9550 on HbA1c compared to placebo(From baseline to Week 24)
- Prevalence, incidence, and titres of ADAs to AZD9550 and AZD6234 in combination(After 24 weeks)
- PD effect of AZD9550 on fasting glucose compared to placebo(From baseline to Week 4)
- PD effect of AZD9550 on fasting lipid profile compared to placebo(From baseline to Week 4)
- Incidence of anti-AZD9550 antibodies(From Day 1 to Day 65)
- PD effect of AZD9550 on fasting glucose compared to placebo(From baseline to Week 5)
- PD effect of AZD9550 on fasting lipid profile compared to placebo(From baseline to Week 5)
- PD effect of AZD9550 on glucose metabolism following an MMTT compared to placebo(From baseline to Week 5)
- Area Under concentration-time Curve of AZD9550 following repeat weekly SC doses(Day 1 to Day 72)
- Incidence of anti-AZD9550 antibodies(Day 1 to Day 72)
- Change in daily (24 hours) average glucose levels as measured by CGM(From baseline to Day 176)
- Change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Weeks 13 and 24)
- Change in 7-day average glucose levels as measured by CGM(From baseline to Weeks 1, 2, 3, 4, 5, and 6 and during 14 days post last dose)
- Change in coefficient of variation of glucose levels as measured by CGM over 7 days(From baseline to Weeks 1, 2, 3, 4, 5, and 6, and during 14 days post last dose)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 24 hours(From baseline to Weeks 1, 2, 3, 4, 5, and 6, and during 14 days post last dose)
- Change in percentage time spent in hyperglycaemia (> 140 mg/dL), normoglycaemia (70 -140 mg/dL), and clinically significant hypoglycaemia (< 54 mg/dL) as measured by CGM over 7 days(From baseline to Weeks 1, 2, 3, 4, 5, and 6, and during 14 days post last dose)
- Percentage change in fasting hepatic glycogen concentration adjusted for liver volume as measured by MRS(From baseline to Week 5)
- Change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Week 5)
- Percentage change in fasting hepatic glycogen concentration unadjusted for liver volume as measured by MRS(From baseline to Week 5)
- Anti-AZD9550 antibody titre among participants with positive serum antibodies to AZD9550(From Day 1 to 65)
- Maximum observed concentration of AZD9550 following repeat weekly SC doses(Day to Day 72)
- Half life associated with terminal phase elimination rate constant of AZD9550 following repeat weekly SC doses(Day 1 to Day 72)
- Time to maximum observed concentration of AZD9550 following repeat weekly SC doses(Day 1 to Day 72)
- Apparent oral clearance of AZD9550 following repeat weekly SC doses(Day 1 to day 72)
- Apparent volume of distribution of AZD9550 following repeat weekly SC doses(Day 1 to Day 72)
- Anti-AZD9550 antibody titre among participants with positive serum antibodies to AZD9550(Day 1 to Day 72)
- PD effect of AZD9550 on glucose metabolism compared to placebo(From baseline to Week 4)
- PD effect of AZD9550 on glucose metabolism compared to placebo(From baseline to Week 5)
- PD effect of AZD9550 on fasting insulin compared to placebo(From baseline to Week 4)
- PD effect of AZD9550 on fasting c-peptide compared to placebo(From baseline to Week 4)
- PD effect of AZD9550 on fasting insulin compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on fasting c-peptide compared to placebo(From baseline to Week 24)
- PD effect of AZD9550 on HbA1c compared to placebo(From baseline to Week 4)
- PD effect of AZD9550 on HbA1c compared to placebo(From baseline to Week 5)