E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To identify the biological mechanisms that mediate Exenatide-effect in the brain, and to measure true treatment-effect of Exenatide that is independent of the concurrent, symptomatic, dopaminergic treatment.
To evaluate the effect on motor-symptom progression. (open-label extension part one).
To evaluate the rate and severity of AEs and the number of AEs related to long-term exposure to Exenatide(open-label extension part two). |
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E.2.2 | Secondary objectives of the trial |
- To compare the effect of Exenatide to placebo on disease progression. - To compare the effect of Exenatide to placebo on motor-symptom progression. - To compare the effect of Exenatide to placebo on the non-motor symptom progression. - To measure the safety of Exenatide in patients with PD. - To evaluate pharmacokinetic properties of Exenatide. - Frequency of adverse events (open-label extension part one). - To evaluate changes in motor, and non-motor symptoms activities of daily living and complications by dopaminergic treatment (open-label extension part one and two ).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of clinically probable Parkinson’s disease. • Males or Females. • Hoehn and Yahr stage ≤ 2 in the ON medication state. • Patients are on levodopa treatment. • No need for extended treatment adjustment, no significant motor fluctuations during the last year. • All patients will be ≥25 and ≤80 years of age. • Ability to self-administer, or to arrange carer administration of the trial drug. • Signed informed consent to participate in the trial. |
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E.4 | Principal exclusion criteria |
• Atypical or other causes of parkinsonism. • Prior intra-cerebral surgical intervention for Parkinson’s disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible. • Already actively participating in a trial of a device, drug or surgical treatment for Parkinson’s disease. • Previous exposure to Exenatide. • Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/FDG-PET acquisition. • Patients with body mass index less than 18.5. • Patients with diabetes mellitus type 1. • Patients with prediabetes, or T2DM. • History of pancreatitis. • Severe gastrointestinal disease including gastroparesis. • History of alcoholism. • History of severe cardiac disease. • History of pancreas cancer. • History or suspicion of thyroid cancer. • Personal or family history of medullary thyroid cancer. • Patients with Multiple Endocrine Neoplasia 2 (MEN2) syndrome. • End-stage renal disease or creatinine clearance < 50 ml/min. • Hyperlipidaemia. • Concurrent treatment with warfarin. • Concurrent severe depression, defined as MADRS score more than 16. • Concurrent dementia, defined as MMSE < 22. • Pregnancy and Breastfeeding. • Known hypersensitivity or allergy or intolerance to GLP-1. • Known hypersensitivity to Exenatide or any of its excipients. • Potential participants who lack the capacity to give informed consent • Any medical, psychiatric or other condition which in the investigator’s opinion compromises the potential participant's ability to participate in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 9 and 21 months |
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E.5.2 | Secondary end point(s) |
A. MDS-UPDRS part 3 in OFF-medication state and accelerometer-based parameters of physical activity, MDS-UPDRS part 3 in ON-medication state, MDS-UPDRS parts 1, 2 and 4, biofluid-based parameters
B. LEDD
C. PDQ-39, NMSQuest, ESS,
D. MoCA
E. B-SIT
F. MADRS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A. Baseline, 9, 18 and 21 months
B. Baseline, 3, 6, 9, 12, 15, 18 and 21 months
C. Baseline, 6, 12, 18 months
D. Baseline, 9 and 21 months
E. Baseline, 9 and 18 months
F. Screening, 6, 12 and 18 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
A double-blind placebo-controlled trial followed by two open-label extensions, part one and part two |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |