Ambroxol in early and prodromal Dementia with Lewybodies

Phase 1

• Conditions: Dementia with Lewy Bodies (DLB) and mild cognitive impairment (MCI) due to Lewy Body Disease (DLB-MCI); MedDRA version: 20.0Level: PTClassification code 10067889Term: Dementia with Lewy bodiesSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-002855-41-NO
• Lead Sponsor: Helse Fonna

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-28
• Last Update Posted: 18 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 172

Inclusion Criteria

1.Male or female.
2.Age = 50 and = 85 years of age.
3.Confirmed diagnosis of Dementia with Lewybodies (DLB) including Mild Cognitive Impairment in DLB (DLB-MCI).
4.MMSE score>=15
5.Able and willing to provide informed consent prior to any study related assessments and procedures.
6.Capable of complying with all study procedures.
7.Willing to provide blood samples for genetic analyses of APOE and GBA
8.Willing and able to self-administer oral ambroxol medication, from day 1 to study end (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 29-550)).
9.Able to travel to the participating study site.
10.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 dementia and PD medications including acetylcholine esterase inhibitors, glutamate antagonists, 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) and indomethacin.
¦Dementia and PD medications as defined above must be on a stable dosing for one month before study start.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

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, argatroban, dabigatraneteksilat, rivaroksaban, apiksaban, edoksaban).
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 this study.
5.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.
6.History of known rare hereditary disorders of galactose
Intolerance: Lapp lactase deficiency or glucose-galactose malabsorption.
7.History of illegal substance abuse, drug abuse or alcoholism in the opinion of the Investigator that would preclude participation in the study.
8.Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of the study drug.
9.Pregnant or breastfeeding.
10.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 2 weeks following the last dose of the study drug.
11.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.
d)Major stroke
e)Major depression or psychotic disorder unrelated to DLB.
f)Cancer or terminal illness.
12.Planned major surgical treatment during the study period.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified