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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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28 February 2019 |
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Main ID: |
EUCTR2015-002571-24-GB |
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Date of registration:
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12/02/2019 |
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Prospective Registration:
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No |
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Primary sponsor: |
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Public title:
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A Pilot Study to Evaluate the Safety, Tolerability (any side effects of the drug) and Pharmacodynamic (biochemical and physiological effects of drugs). The effects of Ambroxol in Patients with Parkinson Disease: Ambroxol in Disease Modification in Parkinson Disease.
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Scientific title:
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A Phase IIA Prospective, Single-Centre, Open Label Clinical Trial to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of Ambroxol in Patients with Parkinson Disease: Ambroxol in Disease Modification in Parkinson Disease
- AiM-PD |
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Date of first enrolment:
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14/10/2016 |
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Target sample size:
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20 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002571-24 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: no
Open: no
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: yes
Other trial design description: A proof of concept clinical trial
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
Number of treatment arms in the trial: 1
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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United Kingdom
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Contacts
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Name:
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Gayle D'Souza
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Address:
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UCL, Institute of Neurology & The National Hospital for Neurology and Neurosurgery
WC1N 3BG
Queen Square, London
United Kingdom |
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Telephone:
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02034484541 |
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Email:
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g.d'souza@ucl.ac.uk |
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Affiliation:
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Leonard Wolfson Experimental Neurology Centre Clinical Research Facility |
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Name:
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Gayle D'Souza
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Address:
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UCL, Institute of Neurology & The National Hospital for Neurology and Neurosurgery
WC1N 3BG
Queen Square, London
United Kingdom |
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Telephone:
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02034484541 |
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Email:
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g.d'souza@ucl.ac.uk |
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Affiliation:
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Leonard Wolfson Experimental Neurology Centre Clinical Research Facility |
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Key inclusion & exclusion criteria
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Inclusion criteria:
1. Male or female;
2. Age = 40 and = 80 years of age;
3. Confirmed diagnosis of Parkinson disease at any time; and Hoehn and Yahr criteria, confirmed staged between I – III, inclusive;
4. Able and willing to provide informed consent prior to any study related assessments and procedures at screening visit 1;
5. Capable of complying with all study procedures, including fasting lumbar puncture;
6. Willing to provide a blood sample for screening genomic for Parkinson Disease related DNA analysis and/or consent to Investigators obtaining and using participants previous DNA results if applicable;
7. Willing and able to self-administer oral ambroxol medication, from day 1 to 186 (at 60 mg TID (day 1-7), 120 mg TID (day 8-14), 180 mg TID (day 15-21), 300 mg TID (day 22-28) and 420 mg TID (day 29-186));
8. Able to travel to the participating study site;
9. A female participant is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12
consecutive months of spontaneous amenorrhea, at least 6 weeks post-surgical
bilateral oophorectomy (with or without hysterectomy) or post tubal
ligation. In questionable cases, menopausal status will be confirmed by
demonstrating levels of follicle stimulating hormone (FSH) 25.8 – 134.8 IU/L
and oestradiol < 201 pmol/l at entry.
• Women of child-bearing potential must use accepted contraceptive methods
(listed below), and must have a negative serum at screening visit 1 and
urine pregnancy tests at subsequent visits if applicable. An additional
pregnancy test will be performed, and results obtained, prior to
administration of the first dose of ambroxol.
Accepted contraception methods:
• True abstinence: When this is in line with the preferred and usual lifestyle of the participant. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).
Contraceptive Methods with a Failure Rate of < 1%:
• Oral contraceptive, either combined or progestogen alone;
• Injectable progestogen;
• Implants of levonorgestrel;
• Estrogenic vaginal ring;
• Percutaneous contraceptive patches; -
• Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label;
Please note:
- All male and female participants of child bearing potential must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 2 weeks following the last dose of the study drug.
- Participants may continue to take PD medications including glutamate antagonists, anticholinergics, dopamine agonists, Levodopa (L-DOPA and decarboxylase (DDC) inhibitor), Monoamine oxidase B (MAO-B) inhibitors catechol-O-methyltransferase (COMT) inhibitors, beta blockers, selective serotonin uptake inhibitors (SSRIS), tricyclic antidepressants (TCAs) a
Exclusion criteria:
Participants are excluded from participating in this study if 1 or more of the following criteria are met:
1. Current treatment with anticoagulants (e.g. warfarin) that might preclude safe completion of the lumbar puncture and in the opinion of the Investigator;
2. Current use of investigational medicinal product or participation in another interventional clinical trial or who have done so within 30 days prior to the first dose in the current study;
3. Exposure to more than three investigational medicinal products within 12 months prior to the first dose in the current study;
4. Confirmed dysphagia that would preclude self-administration of ambroxol up to 7 tablets TID for the duration of day 1 to day 186);
5. Significant known lower spinal malformations or other spinal abnormalities that would preclude lumbar puncture;
6. 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;
7. History of known rare hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
8. Evidence or history of hypersensitivity to lidocaine or its derivatives;
9. History of drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the study;
10. Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of the study drug;
11. Pregnant or breastfeeding;
12. All participants of child bearing potential in the opinion of the Investigator that would preclude participation in the study and who do not agree to use double-barrier birth control or abstinence while participating in the study and for two weeks following the last dose of study drug;
13. Any clinically significant or unstable medical or surgical condition that in the opinion of the PI or PI-delegated clinician may put the participant at risk when participating in the study or may influence the results of the study or affect the participant’s ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests. Such conditions may include:
a) Impaired renal function
b) Moderate/Severe hepatic impairment
c) A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, pulmonary embolism, coronary revascularisation that occurred within 6 months prior to the screening visit.
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
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Parkinson disease
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Intervention(s)
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Trade Name: AMBROSAN 60mg Tablets
Product Name: Ambroxol
Pharmaceutical Form: Tablet
INN or Proposed INN: Ambroxol hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
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Primary Outcome(s)
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Timepoint(s) of evaluation of this end point: The end point is at Month 6
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Secondary Objective: • To assess the safety and tolerability of the Glucocerebrosidase (GCase) modulating chaperone ambroxol in Parkinson disease participants with and without Gaucher gene (GBA) mutation at 5 intra-participant dose escalations from day 1 to 186.
• To measure the pharmacodynamic effects of ambroxol on GCase activity in blood and CSF following ambroxol oral administration at 5 intra-participant dose escalations from day 1 to 186.
• To quantify the effect of ambroxol on biomarkers of Parkinson and neurodegeneration at 5 intra-participant dose escalations from day 1 to 186.
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Primary end point(s): To assess the central nervous system (CNS), cerebrospinal fluid (CSF) penetration by the parameters outlines (GCase activity, ambroxol level) from day 1 to day 186.
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Main Objective: • To assess the central nervous system (CNS), cerebrospinal fluid (CSF) penetration and binding to GCase of ambroxol by the parameters outline (modulation of GCase activity & ambroxol level) at 5 intra-participant dose escalations from day 1 to day 186 at 60 mg TID (day 1-7), 120 mg TID (day 8-14), 180 mg TID (day 15-21), 300 mg TID (day 22-28) and 420 mg TID (day 29-186).
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: The end point is at Month 6
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Secondary end point(s): CSF biomarkers of Parkinson disease and neurodegeneration
CSF ambroxol levels
Safety data, i.e.:
- Adverse events
- Laboratory safety data
- Physical and neurological examinations
- ECG
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Source(s) of Monetary Support
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The Cure Parkinson's Trust
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Ethics review
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Status: Approved
Approval date:
Contact:
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