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

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

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

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: 009-A1; Drug: 009-A2; Drug: 009-A3; Drug: 009-A0; Drug: 009-B1 (active --> placebo) crossover; Drug: 009-B2 (placebo --> active) crossover

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 Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A-1a; Part A, Arm 1 (active), Dose 1 (009-A1)	Drug: 009-A1; Inhaled apomorphine via Staccato aerosol, Dose 1 (low dose) each day for first 5 days, then 3 doses Dose 1 (low dose) q 2 hr on Day 6
EXPERIMENTAL: A-2a; Part A, Arm 2 (active), Dose 2 (009-A2)	Drug: 009-A2; Inhaled apomorphine via Staccato aerosol, Dose 2 (middle dose) each day for first 5 days, then 3 doses Dose 2 (middle dose) q 2 hr on Day 6
EXPERIMENTAL: A-3a; Part A, Arm 3 (active), Dose 3 (009-A3)	Drug: 009-A3; Inhaled apomorphine via Staccato aerosol, Dose 3 (high dose) each day for first 5 days, then 3 doses Dose 3 (high dose) q 2 hr on Day 6
PLACEBO_COMPARATOR: A-0p; Part A, placebo comparator in all 3 arms, placebo dose (009-A0)	Drug: 009-A0; Inhaled placebo via Staccato aerosol, Dose 0 (placebo) each day for first 5 days, then 3 doses Dose 0 (placebo) q 2 hr on Day 6
EXPERIMENTAL: B-1 (009-B3 -> 009-B0); Crossover (active to placebo)	Drug: 009-B1 (active --> placebo) crossover; Up to 2 doses (Dose 3) ; minimum of 2 hrs between doses, on Day 1, followed by Up to 2 doses (placebo) ; minimum of 2 hrs between doses, on Day 2
EXPERIMENTAL: B-1 (009-B0 -> 009-B3); Crossover (placebo to active)	Drug: 009-B2 (placebo --> active) crossover; Up to 2 doses (placebo) ; minimum of 2 hrs between doses, on Day 1, followed by Up to 2 doses (Dose 3) ; minimum of 2 hrs between doses, on Day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A - Dose Proportionality of multi-dose inhaled apomorphine by Power Analysis of AUC	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	6 days
B1 - Effect on MDS-UPDRS in Parkinson's disease OFF periods	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.	2 days
B2 - Effect on Physician Disease State Assessment in Parkinson's disease OFF periods	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.	2 days
B3 - Effect on Patient Assessment of ON/OFF in Parkinson's disease OFF periods	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.	2 days

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Geert J Groeneveld, MD, PhD, Center for Human Drug Research (The Netherlands)

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 16, 2019
• Primary Completion (ACTUAL): February 28, 2020
• Study Completion (ACTUAL): March 6, 2020

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (ACTUAL): November 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: AMDC-009-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes