Safety and pharmacokinetics of multiple dosing with inhalable apomorphine (AZ-009), and its efficacy in a randomized crossover study in Parkinson's disease patients.

Autor: Thijssen E; Centre for Human Drug Research (CHDR), Zernikedreef 8, 2333 CL, Leiden, Netherlands; Leiden University Medical Centre (LUMC), Albinusdreef 2, 2333 ZA, Leiden, Netherlands., den Heijer JM; Centre for Human Drug Research (CHDR), Zernikedreef 8, 2333 CL, Leiden, Netherlands; Leiden University Medical Centre (LUMC), Albinusdreef 2, 2333 ZA, Leiden, Netherlands., Puibert D; Ferrer HealthTech, Diagonal 549, 08029, Barcelona, Spain., van Brummelen EMJ; Centre for Human Drug Research (CHDR), Zernikedreef 8, 2333 CL, Leiden, Netherlands., Naranda T; Alexza Pharmaceuticals, 2091 Stierlin Court, Mountain View, CA, 94043, USA., Groeneveld GJ; Centre for Human Drug Research (CHDR), Zernikedreef 8, 2333 CL, Leiden, Netherlands; Leiden University Medical Centre (LUMC), Albinusdreef 2, 2333 ZA, Leiden, Netherlands. Electronic address: ggroeneveld@chdr.nl.
Jazyk: angličtina
Zdroj: Parkinsonism & related disorders [Parkinsonism Relat Disord] 2022 Apr; Vol. 97, pp. 84-90. Date of Electronic Publication: 2022 Mar 08.
DOI: 10.1016/j.parkreldis.2022.02.014
Abstrakt: Introduction: Apomorphine is used to treat OFF periods in Parkinson's disease (PD) patients. AZ-009 is a novel apomorphine formulation that delivers a thermally-generated aerosol to the deep lung via inhalation with a single breath.
Methods: Part A was a randomized, placebo-controlled, double-blind study investigating the safety and pharmacokinetics of multiple ascending doses of AZ-009. PD patients (n = 24) received placebo or 2, 3 or 4 mg AZ-009 once daily for 5 days, followed by three times daily for 2 days with 2 h between doses. Part B was a double-blind crossover study in 8 PD patients who experience OFF periods. During an OFF state, patients received 4 mg AZ-009 and placebo on two consecutive days in a randomized order. MDS-UPDRS III and ON/OFF state were assessed pre- and post-dose.
Results: Three times daily dosing with 2, 3 and 4 mg AZ-009 was relatively well tolerated with no apparent accumulation or changes in safety profile. Mild and transient throat irritation and cough were reported most often. AZ-009 was rapidly absorbed with median T max between 1 and 2 min. When corrected for placebo response, the maximum effect of 4 mg AZ-009 based on MDS-UPDRS III scores was observed at 10 and 30 min post-dose with mean (SD) reductions of 6.8 (9.4) and 6.1 (9.1) points respectively. Whereas 0% of patients turned ON after placebo, 50% turned ON 10 min after 4 mg AZ-009 treatment.
Conclusion: AZ-009 is rapidly systemically absorbed and safe to dose three times daily. AZ-009 could provide a faster-acting and easier to use formulation than currently available therapies.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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