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

Parkinson's Disease Clinical Trial

— Exenatide-PD3  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04232969
• Other study ID #: 18/0320
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 20, 2020
• Est. completion date: July 31, 2024

Study information

• Verified date: December 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 194
• Est. completion date: July 31, 2024
• Est. primary completion date: February 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Exenatide extended release 2mg (Bydureon)
Subcutaneous Injection

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Timed Walk assessment ON and OFF medication	Assessment with research team	96 weeks
Secondary	Montreal Cognitive Assessment	Questionnaire. Maximum Score= 30. Lower scores indicative of worse outcome.	96 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Levodopa Equivalent Dose	Assessment with Research Team	96 weeks
Secondary	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
Secondary	Safety and tolerability of exenatide as indicated by changes in pulse (bpm)	Vital Signs	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg)	Vital Signs	96 weeks
Secondary	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
Secondary	Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Haematocrit (%)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L)	Full Blood Count	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs)	Blood Tests (Coagulation)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time)	Blood Tests (Coagulation)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs)	Blood Tests (Coagulation)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs)	Blood Tests (Coagulation)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L)	Blood Tests (Coagulation)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin)	Blood Tests (Blood Sugar Levels / Diabetes Testing)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L)	Biochemistry	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL)	Biochemistry (Fasting)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL)	Biochemistry (Fasting)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L)	Biochemistry (Fasting)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L)	Biochemistry (Fasting)	96 weeks
Secondary	Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events	Ongoing Safety Reporting	96 weeks

External Links

•   Sponsor Trial web link