A Phase III, Randomized, Parallel, Double-blind, and Non-inferiority Clinical Trial to Compare Efficacy and Safety of CinnaGen-liraglutide to Innovator Liraglutide Product (Victoza®) in Patients With Type II Diabetes (T2D)
试验速览
- 阶段
- 3 期
- 发起方
- Cinnagen
- 入组人数
- 300
- 主要终点
- HbA1c
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of liraglutide produced by CinnaGen company and Novo Nordisk liraglutide (Victoza®) in subjects with type II diabetes. Patients with Type II diabetes treated with two oral glucose-lowering agents for ≥ 3 months, aged between 30 to 65 years, HbA1c equal or greater than 7.5 and lower than 10, and BMI between 25 to 45 were included in this study.
This study is a phase III, randomized, two-armed, parallel, double-blind, active-controlled, and non-inferiority clinical trial. Patients who enter the trial will be randomly allocated (1:1 ratio) to receive subcutaneous 1.8 mg daily injections of either Victoza® or CinnaGen-liraglutide. Doses of liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks up to 1.8 mg/day from the beginning of the fifth week. Patients continue to receive 1.8 mg/day liraglutide until the end 26th week.
The primary objective of this study is to assess non-inferiority of CinnaGen-liraglutide to reference liraglutide in terms of efficacy in patients with T2D. The secondary objectives of this study are to further compare the efficacy of CinnaGen-liraglutide to reference liraglutide and to assess the safety of CinnaGen-liraglutide to reference liraglutide.
详细描述
The purpose of this study is to compare the efficacy and safety of liraglutide produced by CinnaGen company with Novo Nordisk liraglutide (Victoza®) in subjects with type II diabetes. Patients with Type II diabetes treated with two oral glucose-lowering agents for ≥ 3 months, aged between 30 to 65 years, HbA1c equal or greater than 7.5 and lower than 10, and BMI between 25 to 45 will be included in this study. This study is a phase III, randomized, two-armed, parallel, double-blind, active-controlled, and non-inferiority clinical trial. Patients who enter the trial will be randomly allocated (1:1 ratio) to receive subcutaneous 1.8 mg daily injections of either Victoza® or CinnaGen-liraglutide. Doses of liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks up to 1.8 mg/day from the beginning of the fifth week. Patients continue to receive 1.8 mg/day liraglutide until the end of 26th week.
Physical examinations and vital signs will be evaluated for patients at baseline, and at weeks 4, 8, 12 and 26 visits. Laboratory parameters will be assessed at baseline, week 12 and 26. The incidence of adverse events will be evaluated based on patients' reports, vital signs, physical examinations, and laboratory tests.
Before initiation, the trial will be reviewed by food and drug administration of Iran. The protocol, electronic case report form (eCRF), information for patients and informed consent form will be submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.
In this study, no patient will be recruited without informed consent. All the informed consent forms which will be signed by the patients will have two copies so that patients can receive a copy of it.
Determination of sample size:
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)
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with Type 2 diabetes treated with maximum tolerable dose of two oral glucose-lowering agents (OGLAs; Metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues) for ≥ 3 months
- •30-65 years of age
- •7.5 ≤ HbA1c < 10
- •Body mass index (BMI) of 25-45 kg / m2
排除标准
- •Lack of consent for being in the trial and not complying with 26-weeks follow-up period;
- •Hypersensitivity to liraglutide or any component of the formulation (excipients include Disodium phosphate dehydrate, Propylene glycol, Phenol, Water for injection)
- •Insulin treatment during the previous 3 months (except short-term treatment for intercurrent illness)
- •Impaired liver function (alanine aminotransferase concentrations ≥ 2·5 times upper normal range).
- •Impaired renal function (eGFR < 60 mL/min/1.73 m2),
- •Uncontrolled hypertension (≥ 160/100 mmHg),
- •Malignancy
- •Used any drugs apart from OGLAs likely to affect glucose concentrations, including androgens, hyperglycemia-associated agents, hypoglycemia-associated agents, MAO inhibitors, quinolone antibiotics, salicylates (Anti-inflammatory dose).
- •Treatment with dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors)
- •Treatment with systemic corticosteroids
- •History or family history of Medullary Thyroid Carcinoma (MTC)
- •Multiple endocrine neoplasia syndrome type 2 (MEN2)
- •History of pancreatic cancer and pancreatitis
- •History of recent MI, uncontrolled CHF, and unstable Angina
- •History or known case of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy
- •Pregnancy
- •Previous exposure to exenatide or liraglutide
研究组 & 干预措施
CinnaGen-liraglutide
CinnaGen-liraglutide (Liraglutide 6 MG/ML Pen Injector by CinnaGen Company) will be administered 1.8 mg/day subcutaneously. Doses of CinnaGen-liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Liraglutide 6 MG/ML Pen Injector (Drug)
CinnaGen-liraglutide
CinnaGen-liraglutide (Liraglutide 6 MG/ML Pen Injector by CinnaGen Company) will be administered 1.8 mg/day subcutaneously. Doses of CinnaGen-liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Metformin (Drug)
CinnaGen-liraglutide
CinnaGen-liraglutide (Liraglutide 6 MG/ML Pen Injector by CinnaGen Company) will be administered 1.8 mg/day subcutaneously. Doses of CinnaGen-liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Sulfonylurea/non-sulfonylurea insulin secretagogues (Drug)
Victoza®
Victoza® (Liraglutide 6 MG/ML Pen Injector by Novo Nordisk Company) will be administered 1.8 mg/day subcutaneously. Doses of Victoza® will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Liraglutide 6 MG/ML Pen Injector (Drug)
Victoza®
Victoza® (Liraglutide 6 MG/ML Pen Injector by Novo Nordisk Company) will be administered 1.8 mg/day subcutaneously. Doses of Victoza® will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Metformin (Drug)
Victoza®
Victoza® (Liraglutide 6 MG/ML Pen Injector by Novo Nordisk Company) will be administered 1.8 mg/day subcutaneously. Doses of Victoza® will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
干预措施: Sulfonylurea/non-sulfonylurea insulin secretagogues (Drug)
结局指标
主要结局
HbA1c
时间窗: 26 weeks
The primary outcome of this study is to assess changes in HbA1c in both treatment arms
次要结局
- Systolic blood pressure(26 weeks)
- Fasting blood sugar(26 weeks)
- HbA1c < 7.0%(26 weeks)
- HbA1c ≤ 6.5%(26 weeks)
- Body weight(26 weeks)
- Lipid profiles(26 weeks)
- Postprandial glucose(26 weeks)
- Diastolic blood pressure(26 weeks)
- Liver enzymes(26 weeks)
- Pulse Rate(26 weeks)
- estimated Glomerular Filtration Rate(26 weeks)