Staccato Apomorphine Single and Multi Dose PK

NCT03822364 | Completed Phase 1 FDA Drug

• 1 other identifier: AMDC-009-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

apomorphine; aerosol

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (14)

A-1 (009-1 -> active comparator)

EXPERIMENTAL

Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)

Drug: 009-1; Drug: active comparator

A-2 (active comparator -> 009-1)

EXPERIMENTAL

Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)

Drug: 009-1; Drug: active comparator

B-1a (009-2)

EXPERIMENTAL

Part B, Arm 1 (Inhaled apomorphine, Dose 2)

Drug: 009-2

B-1p (009-0)

PLACEBO COMPARATOR

Part B, Arm 1 (Inhaled placebo)

Drug: 009-0

B-2a (009-3)

ACTIVE COMPARATOR

Part B, Arm 2 (Inhaled apomorphine, Dose 3)

Drug: 009-3

B-2p (009-0)

PLACEBO COMPARATOR

Part B, Arm 2 (Inhaled placebo)

Drug: 009-0

B-3a (009-4)

EXPERIMENTAL

Part B, Arm 3 (Inhaled apomorphine, Dose 4)

Drug: 009-4

B-3p (009-0)

PLACEBO COMPARATOR

Part B, Arm 3 (Inhaled placebo)

Drug: 009-0

C-1a (009-3)

EXPERIMENTAL

Part C, Arm 1 (Inhaled apomorphine, Dose 3)

Drug: 009-3

C-1p (009-0)

PLACEBO COMPARATOR

Part C, Arm 1 (Inhaled placebo)

Drug: 009-0

C-2a (009-4)

EXPERIMENTAL

Part C, Arm 2 (Inhaled apomorphine, Dose 4)

Drug: 009-4

C-2p (009-0)

PLACEBO COMPARATOR

Part C, Arm 2 (Inhaled placebo)

Drug: 009-0

C-3a (009-5)

EXPERIMENTAL

Part C, Arm 3 (Inhaled apomorphine, Dose 5)

Drug: 009-5

C-3p (009-0)

PLACEBO COMPARATOR

Part C, Arm 3 (Inhaled placebo)

Drug: 009-0

Interventions

009-1 DRUG

Inhaled apomorphine via Staccato aerosol, Dose 1

A-1 (009-1 -> active comparator); A-2 (active comparator -> 009-1)

active comparator DRUG

commercially available apomorphine injector

A-1 (009-1 -> active comparator); A-2 (active comparator -> 009-1)

009-0 DRUG

Inhaled placebo via Staccato device

B-1p (009-0); B-2p (009-0); B-3p (009-0); C-1p (009-0); C-2p (009-0); C-3p (009-0)

009-2 DRUG

Inhaled apomorphine via Staccato aerosol, Dose 2

B-1a (009-2)

009-3 DRUG

Inhaled apomorphine via Staccato aerosol, Dose 3

B-2a (009-3); C-1a (009-3)

009-4 DRUG

Inhaled apomorphine via Staccato aerosol, Dose 4

B-3a (009-4); C-2a (009-4)

009-5 DRUG

Inhaled apomorphine via Staccato aerosol, Dose 5

C-3a (009-5)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Center for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Geert J Groeneveld, MD, PhD

  Center for Human Drug Research (The Netherlands)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A 3 part study including: A) Single Dose Crossover in Healthy Volunteers, B) Single Ascending Dose with placebo control in Healthy Volunteers, and C) Single Ascending Dose with placebo control in Subjects with Established Parkinson's Disease

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: January 30, 2019
• Study Start: November 26, 2018
• Primary Completion: March 26, 2019
• Study Completion: March 26, 2019
• Last Updated: August 30, 2019

Record last verified: 2018-12

Locations

NL (1)