A Randomised, Double Blind, Parallel Group, Placebo Controlled, Phase 3 Trial of Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 194
- 试验地点
- 1
- 主要终点
- Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3
研究概览
简要总结
This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, the investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period. In order to explore this, a randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide is being undertaken (Exenatide-PD3).
详细描述
This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period.
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)
盲法说明
Double Blind
入排标准
- 年龄范围
- 25 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Parkinson's disease.
- •Hoehn and Yahr stage ≤2.5 in the ON medication state.
- •Between 25 and 80 years of age.
- •On dopaminergic treatment for at least 4 weeks before enrolment.
- •Ability to self-administer, or to arrange carer administration of trial medication.
- •Documented informed consent to participate.
排除标准
- •Diagnosis or suspicion of other cause for Parkinsonism.
- •Patients unable to attend the clinic visits in the practically defined OFF medication state.
- •Body mass index <18.
- •Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
- •Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
- •Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
- •Prior intra-cerebral surgical intervention for Parkinson's disease.
- •Previous participation in one of the following Parkinson's disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent).
- •Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days
- •Previous exposure to exenatide.
- •Impaired renal function with creatinine clearance <50ml/min.
- •History of pancreatitis.
- •Type 1 or Type 2 diabetes mellitus.
- •Severe gastrointestinal disease (e.g. gastroparesis)
- •Hyperlipidaemia.
- •History or family history of medullary thyroid cancer (MTC).
- •Multiple endocrine neoplasia 2 (MEN2) syndrome.
- •Hypersensitivity to any of exenatide's excipients.
- •Females that are pregnant or breast feeding.
- •WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication.
- •Participants who lack the capacity to give informed consent
- •Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator's opinion compromises the potential participant's ability to participate.
研究组 & 干预措施
Exenatide
Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100
干预措施: Exenatide extended release 2mg (Bydureon) (Drug)
Placebo
Exenatide extended release placebo once weekly for 96 weeks n=100
干预措施: Exenatide extended release 2mg (Bydureon) (Drug)
结局指标
主要结局
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3
时间窗: 96 weeks
Comparison of MDS-UPDRS part 3 motor sub-score in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Min value- 0 Max Value- 108. Higher score indicative of worse outcome.
次要结局
- Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L)(96 weeks)
- Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores.(96 weeks)
- Timed Walk assessment ON and OFF medication(96 weeks)
- Montreal Cognitive Assessment(96 weeks)
- Unified Dyskinesia Rating Scale (UDysRS)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs)(96 weeks)
- Patient Health Questionnaire-9 (PHQ-9)(96 weeks)
- Parkinson's Disease 39 item Quality of life questionnaire(96 weeks)
- Non-Motor Symptoms Scale (NMSS)(96 weeks)
- Levodopa Equivalent Dose(96 weeks)
- 3 day Hauser diary of Parkinson's Disease State(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in pulse (bpm)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Body Mass Index (weight and height will be combined to report BMI in kg/m^2)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Haematocrit (%)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L)(96 weeks)
- Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L)(96 weeks)