A Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Profile of AZ-009 in Subjects with Established Parkinson*s Disease

Completed

Conditions: Parkinson's disease
PD
10028037

Registration Number: NL-OMON48411

Lead Sponsor: Alexza Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

- Subjects between the ages of 30 and 85 (inclusive at the time of signing the
informed consent document) with a clinical diagnosis of PD.

- using medically acceptable contraception during the study and for 90 days
after the last dose of study drug.

- Healthy, as determined by the responsible physician, based on a medical
evaluation including history, physical examination, vital signs,
electrocardiograms (ECGs) and laboratory tests assessed at the screening visit
and prior to the first dose of study drug.

- Part A ONLY: Classified as Hoehn & Yahr stage I-IV in the ON state

- Part B ONLY: Subjects who experience motor fluctuations with recognizable OFF
periods as assessed by the Motor Fluctuation Questionnaire. Subjects should
respond at least one *yes* on the questionnaire.

- Part B ONLY: Classified as Hoehn & Yahr stage I-III in the ON state and have
clear, self-described motor fluctuations (confirmed by the Motor Fluctuation
Questionnaire) on optimized oral l-dopa or dopamine agonist therapy.

Exclusion Criteria

- Use of 5HT3 antagonists

- Previous intolerance to apomorphine

- Symptomatic clinically relevant and medically uncontrolled orthostatic
hypotension.

- Subjects with a prolonged QT interval corrected for heart rate according to
Fridericia's formula (QTcF) of >450 ms for male and >470 ms for female at
screening or directly prior to first dosing, or a history of long QT syndrome.
Also subjects with a PR interval > 220 msec or QRS duration > 120 msec at
screening.

- Active hallucinations or history of hallucinations in the past 3 months. Any
significant medical condition, psychiatric illness or history of depression
that could, in the investigator*s opinion, compromise the subject*s safety or
interfere with the completion of this protocol.

- Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl
transferase (GGT), serum creatinine, or total bilirubin > 1.5 x upper limit of
normal (ULN) at screening or prior to the first dose of study drug. An
exception may be made for a suspected Gilbert*s syndrome.

- Use of medication that is inhibitor or inducer of CYP450-3A4/5 within 3 days
of dosing

- Subjects with a contra-indication for domperidone as per current domperidone
SmPC.

- Use of apomorphine.

- Part B ONLY: Dementia indicated by MMSE <18 at Screening.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part A:<br /><br>- safety and tolerability of AZ-009 after several days of dosing<br /><br>- pharmacokinetics (values of AZ-009 in the blood over time)<br /><br><br /><br>Part B:<br /><br>- safety and tolerability of AZ-009<br /><br>- pharmacokinetics (values of AZ-009 in the blood over time)<br /><br>- effect of AZ-009 when given during an OFF period<br /><br>- user-friendliness of the AZ-009 inhalation device when used during an OFF (by<br /><br>asking the patient)</p><br>

Secondary Outcome Measures