Staccato Apomorphine Multi-dose PK and PD in Patients With Parkinson's Disease

Phase 1

Completed

• Conditions: Parkinson's Disease
• Interventions: Drug: 009-A2; Drug: 009-A0; Drug: 009-B2 (placebo --> active) crossover; Drug: 009-A1; Drug: 009-A3; Drug: 009-B1 (active --> placebo) crossover

• Registration Number: NCT04157933
• Lead Sponsor: Alexza Pharmaceuticals, Inc.

Brief Summary

This study will be conducted in subjects with established Parkinson's disease in 2 parts. Part A will examine the tolerability, safety, and pharmacokinetics of AZ-009 dose escalation ; and Part B will assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of AZ-009 compared with placebo in a crossover design

Detailed Description

This study will be conducted in subjects with established Parkinson's disease in 2 parts.

Part A will examine the tolerability, safety, and pharmacokinetics of daily doses of AZ-009 for 5 days followed by 3 doses on each of days 6 and 7 in dose escalation through 3 cohorts

Part B will assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of AZ-009 compared with placebo in subjects with established Parkinson's disease experiencing regular OFF episodes

Study Timeline

• Status Verified: 2019-08
• Study Start: 2019-10-16
• Study First Submitted: 2019-11-01
• Study First Submitted QC: 2019-11-07
• Study First Posted: 2019-11-08
• Primary Completion: 2020-02-28
• Study Completion: 2020-03-06
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Healthy adult males and females between 30 and 85 years of age, inclusive at the time of signing the informed consent document with a clinical diagnosis of Parkinson's Disease
• Body weight ≥ 50 kg and BMI within the range of 18 to 32 kg/m2.
• Willing and able to be confined at the clinical research center for the study period and adhere to overall study visit schedule, procedures and other protocol requirements.
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

Exclusion Criteria

• 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.
• History of clinically significant central nervous system, cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions including gastric bypass or other weight loss

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A-2a	009-A2	Part A, Arm 2 (active), Dose 2 (009-A2)
A-0p	009-A0	Part A, placebo comparator in all 3 arms, placebo dose (009-A0)
B-1 (009-B0 -> 009-B3)	009-B2 (placebo --> active) crossover	Crossover (placebo to active)
A-1a	009-A1	Part A, Arm 1 (active), Dose 1 (009-A1)
A-3a	009-A3	Part A, Arm 3 (active), Dose 3 (009-A3)
B-1 (009-B3 -> 009-B0)	009-B1 (active --> placebo) crossover	Crossover (active to placebo)

Primary Outcome Measures

Name	Time	Method
A - Dose Proportionality of multi-dose inhaled apomorphine by Power Analysis of AUC	6 days	Dose proportionality of inhaled Staccato apomorphine AUC across all 3 doses during Days 1-5 and multiple daily dosing (all 3 doses q 2 hr per day) on Day 6 using a power model \[regression of log(AUC) versus log(dose)\] in subjects with established Parkinson's disease
B1 - Effect on MDS-UPDRS in Parkinson's disease OFF periods	2 days	Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III in subjects with established Parkinson's disease experiencing regular OFF episodes.
B2 - Effect on Physician Disease State Assessment in Parkinson's disease OFF periods	2 days	Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on the Physician Disease State Assessment in subjects with established Parkinson's disease experiencing regular OFF episodes.
B3 - Effect on Patient Assessment of ON/OFF in Parkinson's disease OFF periods	2 days	Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on Patient Assessment of ON/OFF in subjects with established Parkinson's disease experiencing regular OFF episodes.

Trial Locations

Locations (1)

Centre for Human Drug Research; 🇳🇱 Leiden, Netherlands