A Phase IIb Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Co-administration of AZD9550 and AZD6234 in Participants Living With Obesity or Overweight With Co-morbidity (ASCEND)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 377
- 试验地点
- 54
- 主要终点
- Percent change in body weight from baseline after 36 weeks of treatment
研究概览
简要总结
The purpose of this study is to determine whether treatment with AZD9550 when given in combination with AZD6234 as once weekly subcutaneous (SC) injections is superior to placebo or either agent administered as monotherapy for weight loss in participants living with obesity or overweight with at least one weight-related co-morbidity.
详细描述
This is a Phase IIb, global, randomised, parallel-group, double-blind, placebo-controlled, multi-centre, reduced factorial study designed to evaluate the efficacy, safety and tolerability of treatment with AZD9550 and AZD6234 in combination or as monotherapy in adults who are living with obesity or overweight with at least one of the following weight-related co-morbidities: hypertension, dyslipidemia or obstructive sleep apnoea. The study is composed of a screening period, a treatment period and a follow up period with participants expected to be in the study for approximately 47 weeks. The study will be conducted at around 60 sites and in approximately 7 countries with about, 360 participants will be randomly assigned to study intervention or placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 18 to 75 years of age inclusive.
- •BMI: ≥ 30 kg/m2, or ≥ 27 kg/m2 with at least one weight related comorbidity.
- •A stable, self-reported body weight for 3 months prior to screening.
- •Male and female participants: Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
- •Capable of giving signed informed consent.
排除标准
- •History of any clinically important disease or disorder, which, in the opinion of the Investigator, may put the participant at risk.
- •History or presence of GI, renal, hepatic disease.
- •Previous or planned bariatric surgery or fitting of a weight loss device.
- •Obesity induced by endocrine disorders such as Cushing's syndrome, insulinoma or Prader-Willi syndrome.
- •History of T1DM or T2DM or symptoms indicative of insulinopenia or poor glucose control.
- •HbA1c ≥ 6.5% (48 mmol/mol), fasting serum glucose ≥ 126 mg/dL (7.0 mmol/L) or random glucose ≥ 200 mg/dL (11.1 mmol/L).
- •Significant gastric and hepatobiliary disease.
- •History of acute or chronic pancreatitis or pancreatic amylase or lipase > 2 × ULN at screening.
- •History of psychosis or bipolar disorder.
- •History of major depressive disorder within the 2 years prior to screening or depression.
- •Treatment with a GLP1 containing preparation, either as part of treatment or while participating in another clinical study within the 3 months or 5 half-lives of the drug prior to screening.
- •Vulnerable populations
研究组 & 干预措施
Arm 1
AZD9550 low dose + AZD6234 low dose or placebos
干预措施: Placebo comparator (Drug)
Arm 1
AZD9550 low dose + AZD6234 low dose or placebos
干预措施: AZD9550 (Drug)
Arm 1
AZD9550 low dose + AZD6234 low dose or placebos
干预措施: AZD6234 (Drug)
Arm 4
AZD9550 low dose + AZD6234 medium dose or placebos
干预措施: AZD9550 (Drug)
Arm 8
AZD9550 high dose or placebo
干预措施: AZD9550 (Drug)
Arm 3
AZD9550 high dose + AZD6234 high dose or placebos
干预措施: Placebo comparator (Drug)
Arm 9
AZD6234 high dose or placebo
干预措施: Placebo comparator (Drug)
Arm 3
AZD9550 high dose + AZD6234 high dose or placebos
干预措施: AZD9550 (Drug)
Arm 2
AZD9550 medium dose + AZD6234 medium dose or placebos
干预措施: Placebo comparator (Drug)
Arm 4
AZD9550 low dose + AZD6234 medium dose or placebos
干预措施: Placebo comparator (Drug)
Arm 5
AZD9550 medium dose + AZD6234 low dose or placebos
干预措施: Placebo comparator (Drug)
Arm 6
AZD9550 high dose + AZD6234 medium dose or placebos
干预措施: Placebo comparator (Drug)
Arm 7
AZD9550 medium dose + AZD6234 high dose or placebos
干预措施: Placebo comparator (Drug)
Arm 8
AZD9550 high dose or placebo
干预措施: Placebo comparator (Drug)
Arm 7
AZD9550 medium dose + AZD6234 high dose or placebos
干预措施: AZD6234 (Drug)
Arm 2
AZD9550 medium dose + AZD6234 medium dose or placebos
干预措施: AZD6234 (Drug)
Arm 7
AZD9550 medium dose + AZD6234 high dose or placebos
干预措施: AZD9550 (Drug)
Arm 5
AZD9550 medium dose + AZD6234 low dose or placebos
干预措施: AZD9550 (Drug)
Arm 3
AZD9550 high dose + AZD6234 high dose or placebos
干预措施: AZD6234 (Drug)
Arm 6
AZD9550 high dose + AZD6234 medium dose or placebos
干预措施: AZD6234 (Drug)
Arm 6
AZD9550 high dose + AZD6234 medium dose or placebos
干预措施: AZD9550 (Drug)
Arm 5
AZD9550 medium dose + AZD6234 low dose or placebos
干预措施: AZD6234 (Drug)
Arm 4
AZD9550 low dose + AZD6234 medium dose or placebos
干预措施: AZD6234 (Drug)
Arm 2
AZD9550 medium dose + AZD6234 medium dose or placebos
干预措施: AZD9550 (Drug)
Arm 9
AZD6234 high dose or placebo
干预措施: AZD6234 (Drug)
结局指标
主要结局
Percent change in body weight from baseline after 36 weeks of treatment
时间窗: 36 weeks
To determine whether treatment with AZD9550 and AZD6234 in combination is superior to placebo for weight loss
Weight loss ≥ 5% from baseline after 36 weeks of treatment
时间窗: 36 weeks
To assess the effect of treatment with AZD9550 and AZD6234 in combination vs placebo on the proportion of participants with weight loss ≥ 5%
次要结局
- Incidence of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment(36 weeks)
- Absolute change in body weight from baseline after 36 weeks of treatment(36 weeks)
- Weight loss ≥ 5% from baseline after 36 weeks of treatment(36 weeks)
- Weight loss ≥ 10% and ≥ 15% from baseline after 36 weeks of treatment(36 weeks)
- Percent change in body weight from baseline after 36 weeks of treatment(36 weeks)
- Titres of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment(36 weeks)
- Prevalence of ADAs to AZD9550 and AZD6234 in combination and as monotherapies after 36 weeks of treatment(36 weeks)