Staccato Apomorphine Single and Multi Dose PK

A Randomized Study of the Safety, Tolerability, and Pharmacokinetics of AZ-009 (Staccato Apomorphine) in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZ-009 in Subjects With Parkinson's Disease

This study will be conducted in 3 parts. A) compare the pharmacokinetics (PK) of a single dose of AZ-009 with that of a therapeutically-relevant dose of a commercially available apomorphine injector in healthy volunteers; B) ascending doses of active drug in healthy volunteers; and C) examine the tolerability, safety, and PK of AZ-009 in subjects with established Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: 009-1; Drug: active comparator; Drug: 009-2; Drug: 009-0; Drug: 009-3; Drug: 009-4; Drug: 009-5

Detailed Description

This study will be conducted in 3 parts. Parts A and B will be conducted in healthy volunteers and Part C will be conducted in subjects with established Parkinson's disease. The primary objectives for each part are as follows.

Part A: To compare the pharmacokinetics of a single low dose of AZ-009 with that of a therapeutically-relevant dose a commercially available apomorphine injector in healthy volunteers.

Part B: To examine the tolerability and safety of AZ-009 of single ascending doses of active drug in healthy volunteers while; and to characterize the pharmacokinetics of single ascending doses of AZ-009 in healthy volunteers

Part C: To examine the tolerability, safety, and pharmacokinetics of AZ-009 in subjects with established Parkinson's disease and to identify optimal doses to bring into multiple ascending dose safety and efficacy studies; and to assess the usability of AZ-009 in subjects with Parkinson's Disease

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Center for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult males and females between 18 and 60 years of age, inclusive at the time of signing the informed consent document.
• 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 surgical procedure; or history of such conditions that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial.
• Use of non-prescription medications within 5 days prior to the first dose of study drug.
• Use of medication that is inhibitor or inducer of CYP450-3A4/5 within 3 days of dosing.
• Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, within 3 days prior to administration of study drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A-1 (009-1 -> active comparator); Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)	Drug: 009-1; Inhaled apomorphine via Staccato aerosol, Dose 1; Drug: active comparator; commercially available apomorphine injector
EXPERIMENTAL: A-2 (active comparator -> 009-1); Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)	Drug: 009-1; Inhaled apomorphine via Staccato aerosol, Dose 1; Drug: active comparator; commercially available apomorphine injector
EXPERIMENTAL: B-1a (009-2); Part B, Arm 1 (Inhaled apomorphine, Dose 2)	Drug: 009-2; Inhaled apomorphine via Staccato aerosol, Dose 2
PLACEBO_COMPARATOR: B-1p (009-0); Part B, Arm 1 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device
ACTIVE_COMPARATOR: B-2a (009-3); Part B, Arm 2 (Inhaled apomorphine, Dose 3)	Drug: 009-3; Inhaled apomorphine via Staccato aerosol, Dose 3
PLACEBO_COMPARATOR: B-2p (009-0); Part B, Arm 2 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device
EXPERIMENTAL: B-3a (009-4); Part B, Arm 3 (Inhaled apomorphine, Dose 4)	Drug: 009-4; Inhaled apomorphine via Staccato aerosol, Dose 4
PLACEBO_COMPARATOR: B-3p (009-0); Part B, Arm 3 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device
EXPERIMENTAL: C-1a (009-3); Part C, Arm 1 (Inhaled apomorphine, Dose 3)	Drug: 009-3; Inhaled apomorphine via Staccato aerosol, Dose 3
PLACEBO_COMPARATOR: C-1p (009-0); Part C, Arm 1 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device
EXPERIMENTAL: C-2a (009-4); Part C, Arm 2 (Inhaled apomorphine, Dose 4)	Drug: 009-4; Inhaled apomorphine via Staccato aerosol, Dose 4
PLACEBO_COMPARATOR: C-2p (009-0); Part C, Arm 2 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device
EXPERIMENTAL: C-3a (009-5); Part C, Arm 3 (Inhaled apomorphine, Dose 5)	Drug: 009-5; Inhaled apomorphine via Staccato aerosol, Dose 5
PLACEBO_COMPARATOR: C-3p (009-0); Part C, Arm 3 (Inhaled placebo)	Drug: 009-0; Inhaled placebo via Staccato device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration	Relative bioavailability of inhaled Staccato apomorphine compared to active comparator injection based on the Geometric Least Squares Mean Ratio of AUCinf for all subjects completing the crossover part of the trial	24 hours
B-Dose Proportionality by Power Analysis of AUCinf	Dose proportionality of inhaled Staccato apomorphine AUCinf across all doses administered in the single ascending dose portions of the study (Parts B and C) using a power model [regression of log(AUCinf) versus log(dose)]	24 hours

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): November 26, 2018
• Primary Completion (ACTUAL): March 26, 2019
• Study Completion (ACTUAL): March 26, 2019

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (ACTUAL): January 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 30, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: aerosol; apomorphine
• 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-009-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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