Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease (Exenatide-PD3)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Exenatide extended release 2mg (Bydureon)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • University College London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of Parkinson's disease.
2. Hoehn and Yahr stage ≤2.5 in the ON medication state.
3. Between 25 and 80 years of age.
4. On dopaminergic treatment for at least 4 weeks before enrolment.
5. Ability to self-administer, or to arrange carer administration of trial medication.
6. Documented informed consent to participate.

Exclusion Criteria:

1. Diagnosis or suspicion of other cause for Parkinsonism.
2. Patients unable to attend the clinic visits in the practically defined OFF medication state.
3. Body mass index <18.5.
4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
7. Prior intra-cerebral surgical intervention for Parkinson's disease.
8. 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).
9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days
10. Previous exposure to exenatide.
11. Impaired renal function with creatinine clearance <50ml/min.
12. History of pancreatitis.
13. Type 1 or Type 2 diabetes mellitus.
14. Severe gastrointestinal disease (e.g. gastroparesis)
15. Hyperlipidaemia.
16. History or family history of medullary thyroid cancer (MTC).
17. Multiple endocrine neoplasia 2 (MEN2) syndrome.
18. Hypersensitivity to any of exenatide's excipients.
19. Females that are pregnant or breast feeding.
20. 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.
21. Participants who lack the capacity to give informed consent
22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator's opinion compromises the potential participant's ability to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Exenatide; Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100	Drug: Exenatide extended release 2mg (Bydureon); Subcutaneous Injection
Placebo Comparator: Placebo; Exenatide extended release placebo once weekly for 96 weeks n=100	Drug: Exenatide extended release 2mg (Bydureon); Subcutaneous Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3	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.	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores.	Questionnaire. Section I: 16 points; Section II: 52; Section IV: 23. Higher score indicative of worse outcome.	96 weeks
Timed Walk assessment ON and OFF medication	Assessment with research team	96 weeks
Montreal Cognitive Assessment	Questionnaire. Maximum Score= 30. Lower scores indicative of worse outcome.	96 weeks
Unified Dyskinesia Rating Scale (UDysRS)	Questionnaire. The UDysRS has four parts: I: Historical Disability (patient perceptions) of On-Dyskinesia impact (maximum 44 points); II: Historical Disability (patient perceptions) of Off-Dystonia impact (maximum 16 points); III: Objective Impairment (dyskinesia severity, anatomical distribution over seven body regions, and type (choreic or dystonic) based on four activities observed or video-recorded (28 points); IV: Objective Disability based on Part III activities (maximum 16 points). Higher scores= worse outcomes	96 weeks
Patient Health Questionnaire-9 (PHQ-9)	Questionnaire. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. Max Score= 27. Higher Score= worse outcome	96 weeks
Parkinson's Disease 39 item Quality of life questionnaire	This questionnaire assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living. The 39 item questionnaire offers a patient reported measure of health status and quality of life and is the most frequently used disease-specific health status measure. Higher score= worse outcome.	96 weeks
Non-Motor Symptoms Scale (NMSS)	Questionnaire. The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD. Higher score indicative of worse outcome. NMSS total score is 0 to 360.	96 weeks
Levodopa Equivalent Dose	Assessment with Research Team	96 weeks
3 day Hauser diary of Parkinson's Disease State	Participant take Home questionnaire. (Time-On, Off, Non troublesome Dyskinesia, Troublesome dyskinesia, Asleep). Higher total scores indicate more severe motor signs of Parkinson's.	96 weeks
Safety and tolerability of exenatide as indicated by changes in pulse (bpm)	Vital Signs	96 weeks
Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg)	Vital Signs	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)	Vital Signs	96 weeks
Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Haematocrit (%)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L)	Full Blood Count	96 weeks
Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs)	Blood Tests (Coagulation)	96 weeks
Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time)	Blood Tests (Coagulation)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs)	Blood Tests (Coagulation)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs)	Blood Tests (Coagulation)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L)	Blood Tests (Coagulation)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin)	Blood Tests (Blood Sugar Levels / Diabetes Testing)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L)	Biochemistry	96 weeks
Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL)	Biochemistry (Fasting)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL)	Biochemistry (Fasting)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L)	Biochemistry (Fasting)	96 weeks
Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L)	Biochemistry (Fasting)	96 weeks
Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events	Ongoing Safety Reporting	96 weeks

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Tom Foltynie, University College London Comprehensive Clinical Trials Unit

Publications and helpful links

General Publications

• Vijiaratnam N, Girges C, Auld G, Chau M, Maclagan K, King A, Skene S, Chowdhury K, Hibbert S, Morris H, Limousin P, Athauda D, Carroll CB, Hu MT, Silverdale M, Duncan GW, Chaudhuri R, Lo C, Del Din S, Yarnall AJ, Rochester L, Gibson R, Dickson J, Hunter R, Libri V, Foltynie T. Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson's disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The 'Exenatide-PD3' study. BMJ Open. 2021 May 28;11(5):e047993. doi: 10.1136/bmjopen-2020-047993.

Helpful Links

• Sponsor Trial web link

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Estimated): February 24, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: January 10, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Exenatide; Parkinson's research
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 18/0320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No