Высокие дозы амброксола при паркинсонизме, связанном с GBA1

Daily administration of Ambroxol in newly diagnosed GBA1 PD.

75mg slow release (SR), X16/day or 300mg X4/day oral capsules.

The outcome measure involves the assessment of adverse events (AEs) experienced by study participants throughout the duration of the trial. Adverse events will be documented, and their severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. This comprehensive evaluation aims to provide a clear understanding of the safety profile of the intervention by specifically measuring and reporting the incidence and severity of treatment-emergent adverse events.

Criteria for potentially clinically significant abnormalities (PCSA): Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (Male[M]) or <=95 g/L (Female[F]), greater than or equal to (>=) 185 g/L (M) or >=165 g/L (F), Decrease from baseline (DFB) >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) (M) or <=0.32 v/v (F), >=0.55 v/v (M) or >=0.5 v/v (F); Red blood cells (RBC): >=6 Tera/L; Platelets: less than (<) 100 Giga/L, >=700 Giga/L; White blood cells (WBC): <3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]), >=16.0 Giga/L; Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); Lymphocytes: <lower limit of normal (LLN), greater than (>) 4.0 Giga/L; Monocytes: <LLN, >0.7 Giga/L; Basophils: >0.1 Giga/L; Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L).

Criteria for PCSA: Alanine Aminotransferase (ALT): >3 ULN, >5 ULN; Aspartate aminotransferase (AST): >3 ULN; Alkaline phosphatase: >1.5 ULN; Total Bilirubin: >1.5 ULN; ALT and Bilirubin: >3 ULN and >2 ULN; Direct Bilirubin and Bilirubin: >35% and >1.5 ULN.

Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L) (adults), >=30% change from baseline, >=100% change from baseline; Blood urea nitrogen: >=17 millimoles (mmol)/L.

Criteria for PCSA: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]); Albumin: <=25 g/L.

Criteria for PCSA: Sodium: <=129 mmol/L, >=160 mmol/L; Potassium: <3 mmol/L, >=5.5 mmol/L and Chloride: <80 mmol/L, >115 mmol/L.

Criteria for PCSA: Systolic blood pressure (SBP) supine: <=95 millimeters of mercury (mmHg) and DFB >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg; Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg; SBP (Orthostatic): <=-20 mmHg; DBP (Orthostatic): <=-10 mmHg; Heart rate (HR) supine: <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm; Weight: >=5% DFB; >=5% IFB.

Routine physical examinations will be conducted to assess participants for any physical manifestations of adverse effects or safety concerns.

In the final report the number of participants with new abnormal physical examination findings will be reported.

Transcranial Ultrasonography detects the area of hyper-echogenicity in the region of substantia nigra (values greater than 0.2 cm square are considered abnormal.

Improvement from baseline will be assessed and considered significant if greater than 15% from baseline.

Change from baseline to end of study (EOS) in F-DOPA imaging will be qualitative as assessed by independent expert in nuclear medicine in a central imaging center.

Using: (Video-recorded unified Parkinson's disease rating scale (MDS-UPDRS) Part II and III.

Perdue pegboard

Trail Making Test (TMT)

Montreal Cognitive Assessment (MoCa)

NeuroTrax

Clinical Global Impression Scale (CGI)

Hooper Visual Organization Test (VOT)

Beck Depression inventory (BDI)

REM sleep behavior disorder (RBD)

Epworth sleepiness scale (ESS)

Using the following tests: the BIT University of Pennsylvania brief Smell Identification Test (UPSIT)

Constipation questionnaire

Orthostatic hypotension (OH)

Color discrimination.