NCT05778617

Brief Summary

This is a UK only clinical trial in patients with Parkinson's disease (PD) of a drug called ambroxol hydrochloride, which is an already licensed drug for the treatment of respiratory conditions (such as a common cold) in many European countries. The aim of this trial is to find out whether ambroxol hydrochloride can slow down the progression of Parkinson's disease and to evaluate it's safety and tolerability.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
330

participants targeted

Target at P50-P75 for phase_3 parkinson-disease

Timeline
40mo left

Started Feb 2025

Typical duration for phase_3 parkinson-disease

Geographic Reach
1 country

15 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress27%
Feb 2025Sep 2029

First Submitted

Initial submission to the registry

February 16, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 21, 2023

Completed
1.9 years until next milestone

Study Start

First participant enrolled

February 25, 2025

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2029

Expected
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2029

Last Updated

May 1, 2025

Status Verified

April 1, 2025

Enrollment Period

3.9 years

First QC Date

February 16, 2023

Last Update Submit

April 30, 2025

Conditions

Keywords

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersNeurodegenerative DiseasesAmbroxolSynucleinopathies

Outcome Measures

Primary Outcomes (1)

  • Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I- III score from baseline to Week 104.

    The MDS-UPDRS is a comprehensive 50 question assessment of both motor and non-motor symptoms associated with Parkinson's. Comparison of MDS-UPDRS Parts I-III total score at 104 weeks between participants according to treatment allocation will be made. Parts I and II are measured in the practically defined ON medication state and Part III is measured in the practically defined OFF medication state. Parts I and II are historical data assessed by an examiner and are designed to rate mentation, behaviour and mood; Part III is done as a motor examination at the time of a visit. Participants will undergo MDS-UPDRS assessment at baseline, week 20, week 40, week 60, week 80, week 104. The MDS-UPDRS measures patient status on a scale 0, which is normal or none, to 4, which is severe or the worst scenario. MDS-UPDRS score = sum of Parts I, II and III (Range: 0 to 236). Higher score indicative of worse outcome.

    Baseline; Week 104

Secondary Outcomes (43)

  • Motor signs of PD using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score in the OFF medication state from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104.

  • Motor complications of PD using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV score in the ON medication state from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104.

  • The non-motor impact of PD on patients using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I score in the ON medication state baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104.

  • The motor aspect impact of PD of patients experiences on daily living using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II score in the ON medication state from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104.

  • The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) tremor score from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104.

  • +38 more secondary outcomes

Other Outcomes (7)

  • The association between ambroxol, the glucocerebrosidase enzyme and other proteins associated with the development of PD measured by glucocerebrosidase enzyme activity and other protein markers in blood and cerebrospinal fluid (CSF) samples.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104

  • The association between ambroxol and alpha-synuclein levels in blood and cerebrospinal fluid (CSF) samples from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104

  • The association between ambroxol and glycerylceramide, neurofilament light chain and lipid levels in cerebrospinal fluid (CSF) samples from baseline to Week 104.

    Baseline; Week 20; Week 40; Week 60; Week 80; Week 104

  • +4 more other outcomes

Study Arms (2)

Ambroxol hydrochloride

ACTIVE COMPARATOR

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

Drug: Ambroxol Hydrochloride (420mg)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Oral tablet

Also known as: Ambroxol
Ambroxol hydrochloride

Oral tablet

Placebo

Eligibility Criteria

Age35 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • Adults aged ≥ 35 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.

You may not qualify if:

  • 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.
  • 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:
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

University Hospitals Birmingham

Birmingham, United Kingdom

NOT YET RECRUITING

Southmead Hospital Bristol

Bristol, United Kingdom

NOT YET RECRUITING

Addenbrookes NHS Trust

Cambridge, United Kingdom

NOT YET RECRUITING

Western General Hospital

Edinburgh, United Kingdom

NOT YET RECRUITING

Kings College London

London, United Kingdom

NOT YET RECRUITING

Royal London Hospital

London, United Kingdom

NOT YET RECRUITING

University College London Hospital's

London, United Kingdom

RECRUITING

Newcastle

Newcastle, United Kingdom

NOT YET RECRUITING

Northumbria

Newcastle upon Tyne, United Kingdom

NOT YET RECRUITING

The John Radcliffe Hospital

Oxford, United Kingdom

NOT YET RECRUITING

Derriford Hospital

Plymouth, United Kingdom

RECRUITING

Fairfield General Hospital

Salford, United Kingdom

NOT YET RECRUITING

Salford Royal Hospital

Salford, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, United Kingdom

NOT YET RECRUITING

Prince Philip Hospital

Wales, United Kingdom

NOT YET RECRUITING

Related Links

MeSH Terms

Conditions

Parkinson DiseaseParkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersNeurodegenerative DiseasesSynucleinopathies

Interventions

Ambroxol

Condition Hierarchy (Ancestors)

Proteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

BromhexineAniline CompoundsAminesOrganic ChemicalsCyclohexylamines

Study Officials

  • Anthony Schapira

    University College, London

    PRINCIPAL INVESTIGATOR

Central Study Contacts

ASPro-PD Trial Team

CONTACT

Felicia Ikeji

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double Blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: A randomised, double blind, parallel group, placebo controlled, Phase 3a trial of daily ambroxol hydrochloride (420mg) as a potential disease modifying treatment for Parkinson's disease.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 16, 2023

First Posted

March 21, 2023

Study Start

February 25, 2025

Primary Completion (Estimated)

February 1, 2029

Study Completion (Estimated)

September 1, 2029

Last Updated

May 1, 2025

Record last verified: 2025-04

Locations