Ambroxol to Slow Progression in Parkinson Disease

Inclusion Criteria:

1. A diagnosis of Parkinson's disease (in accordance with the MDS diagnostic criteria)within 7 years of the screening visit confirmed by year of diagnosis.

2. Adults aged ≥ 35 and ≤ 75 years.

3. Hoehn and Yahr stage between 1-2.5, inclusive (in ON stage) at screening visit.

4. Known glucocerebrosidase gene (GBA1) status, positive or negative (status MUST beconfirmed prior to screening).

5. On stable dopaminergic treatment for at least 3 months before enrolment.

6. Able and willing to provide informed consent prior to any study related assessmentsand/or procedures.

7. Able and willing to attend trial visits and comply with all study procedures for theduration of the trial.

8. Willing and able to self-administer oral ambroxol medication or placebo.

Exclusion Criteria:

1. Participation in another interventional clinical trial of an InvestigationalMedicinal Product (IMP) and use of an Investigational Medicinal Product (IMP) within 90 days prior to the first dose of trial treatment.

2. Use of an Investigational Medicinal Product (IMP) within 90 days prior to the firstdose of trial treatment.

3. Participation in another clinical trial of an Investigational New Drug being testedfor PD disease modifying potential within 12 months prior to the first dose of trialtreatment.

4. Past surgical history of deep brain stimulation.

5. Use of ambroxol in the past 12 months.

6. Exposure to Exenatide within 12 months prior to the first dose in this currenttrial.

7. Concomitant medications that in the opinion of the Investigator would precludeparticipation in the study e.g., exenatide or other GLP1 agonist for diabetes.

8. Confirmed dysphagia that would preclude self-administration of ambroxol.

9. History of known sensitivity to the study medication, ambroxol or its excipients (lactose monohydrate, granulated microcrystalline cellulose, copovidone andmagnesium stearate) in the opinion of the investigator that contraindicates theirparticipation.

10. History of known rare hereditary disorders of galactose intolerance, Lapp lactasedeficiency or glucose-galactose malabsorption.

11. Presence of the LRRK2 G2019S mutation (status to be confirmed prior to screening).

12. History of drug abuse or alcoholism in the opinion of the Investigator that wouldpreclude participation in the trial.

13. Pregnant (or planned pregnancy during the trial) and/or breastfeeding.

14. Women of childbearing potential (WOCBP) and male participants with a partner ofchildbearing potential not willing to use highly effective contraception orabstinence for the duration of the trial treatment and for 2 weeks following thelast dose of the study drug.

15. Any clinically significant or unstable medical or surgical condition that in theopinion of the Investigator may; put the participant at risk when participating inthe study, influence the results of the study or affect the participants ability totake part in the study, as determined by medical history, physical examinations,electrocardiogram (ECG) or laboratory tests. Such conditions may include: A. Impaired renal function with creatinine clearance <50ml/min at screening visit. B. Moderate/Severe hepatic impairment. C. A major cardiovascular event (e.g., myocardial infarction, acute coronarysyndrome, compensated congestive heart failure, pulmonary embolism, coronaryrevascularisation) that occurred within 6 months prior to the screening visit.

16. Severe depression defined by a score >20 on the Beck Depression Inventory-II (BDI-II) at screening.

17. Significant cognitive impairment defined by a score <20 on the Montreal CognitiveAssessment (MoCA) at screening.

18. Use of trihexyphenidyl or benztropine within 30 days prior to the first dose oftrial treatment.

19. Only applicable for those patients consenting to the optional CSF sub-study:Evidence or history of hypersensitivity to lidocaine or its derivatives.

20. Only applicable for those patients consenting to the optional CSF sub-study: currenttreatment with anti-coagulants (e.g., warfarin) that might preclude safe completionof the lumbar puncture in the opinion of the Investigator. Aspirin will bepermitted.

21. Only applicable for those patients consenting to the optional CSF sub-study:Significant known lower spinal malformations or other spinal abnormalities thatwould preclude a lumbar puncture.