Ambroxol to Slow Progression in Parkinson Disease (ASPro-PD)
Parkinson Disease
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinsonian Disorders, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases, Ambroxol, Synucleinopathies
Eligibility Criteria
Inclusion Criteria: Diagnosis of Parkinson's disease (in accordance with the MDS diagnostic criteria) within 7 years Adults aged ≥ 40 and ≤ 75 years. Hoehn and Yahr stage between 1-2.5, inclusive (in ON stage) at screening visit. Known glucocerebrosidase gene (GBA1) status, positive or negative (status MUST be confirmed prior to screening). On stable dopaminergic treatment for at least 3 months before enrolment. Able and willing to provide informed consent prior to any study related assessments and/or procedures. Able and willing to attend trial visits and comply with all study procedures for the duration of the trial. Willing and able to self-administer oral ambroxol medication or placebo. Exclusion Criteria: Participation in another interventional clinical trial of an Investigational Medicinal Product (IMP) and use of an Investigational Medicinal Product (IMP) within 90 days prior to the first dose of trial treatment. Participation in another clinical trial of an Investigational New Drug being tested for PD disease modifying potential within 12 months prior to the first dose of trial treatment. Past surgical history of deep brain stimulation. Use of ambroxol in the past 12 months. Exposure to Exenatide within 12 months prior to the first dose in this current trial. Concomitant medications that in the opinion of the Investigator would preclude participation in the study e.g., exenatide or other GLP1 agonist for diabetes. Confirmed dysphagia that would preclude self-administration of ambroxol. History of known sensitivity to the study medication, ambroxol or its excipients (lactose monohydrate, granulated microcrystalline cellulose, copovidone and magnesium stearate) in the opinion of the investigator that contraindicates their participation. History of known rare hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Presence of the LRRK2 G2019S mutation (status to be confirmed prior to screening). History of drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the trial. Pregnant (or planned pregnancy during the trial) and/or breastfeeding. Women of childbearing potential (WOCBP) and male participants with a partner of childbearing potential not willing to use highly effective contraception or abstinence for the duration of the trial treatment and for 2 weeks following the last dose of the study drug. Any clinically significant or unstable medical or surgical condition that in the opinion of the Investigator may; put the participant at risk when participating in the study, influence the results of the study or affect the participants ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG) or laboratory tests. Such conditions may include: Impaired renal function with creatinine clearance <50ml/min at screening visit. Moderate/Severe hepatic impairment A major cardiovascular event (e.g., myocardial infarction, acute coronary syndrome, compensated congestive heart failure, pulmonary embolism, coronary revascularisation) that occurred within 6 months prior to the screening visit. Severe depression defined by a score >20 on the Beck Depression Inventory-II (BDI-II) at screening. Significant cognitive impairment defined by a score <20 on the Montreal Cognitive Assessment (MoCA) at screening. Use of Anticholinergic (e.g. trihexyphenidyl) within 30 days prior to the first dose of trial treatment. Only applicable for those patients consenting to the optional CSF sub-study: Evidence or history of hypersensitivity to lidocaine or its derivatives. Only applicable for those patients consenting to the optional CSF sub-study: current treatment with anti-coagulants (e.g., warfarin) that might preclude safe completion of the lumbar puncture in the opinion of the Investigator. Aspirin will be permitted. Only applicable for those patients consenting to the optional CSF sub-study: Significant known lower spinal malformations or other spinal abnormalities that would preclude a lumbar puncture.
Sites / Locations
- Addenbrookes NHS Trust
- North Cumbria Integrated Care NHS Foundation Trust
- University College London Hospital's
- The John Radcliffe Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Ambroxol hydrochloride
Placebo
Participants will receive ambroxol hydrochloride (tablets) for 104 weeks (blinded treatment period). Participants will receive ambroxol hydrochloride 420mg daily for Days 1-5, then 840mg daily for Days 6-10, then 1260mg for the remainder of the blinded treatment period. Participants will then enter the open-label extension and will receive ambroxol hydrochloride 420mg daily for Days 1-5, then 840mg daily for Days 6-10, then 1260mg for the remainder of the open-label extension phase. n=165
Participants will receive ambroxol hydrochloride matching placebo (tablets) for 104 weeks (blinded treatment period). Participants will receive ambroxol hydrochloride matching placebo 420mg daily for Days 1-5, then 840mg daily for Days 6-10, then 1260mg for the remainder of the blinded treatment period. Participants will then enter the open-label extension and will receive ambroxol hydrochloride 420mg daily for Days 1-5, then 840mg daily for Days 6-10, then 1260mg for the remainder of the open-label extension phase. n=165