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Staccato Apomorphine Single and Multi Dose PK

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
009-1
active comparator
009-0
009-2
009-3
009-4
009-5
Sponsored by
Alexza Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring apomorphine, aerosol

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Center for Human Drug Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Active Comparator

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

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

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

B-1a (009-2)

B-1p (009-0)

B-2a (009-3)

B-2p (009-0)

B-3a (009-4)

B-3p (009-0)

C-1a (009-3)

C-1p (009-0)

C-2a (009-4)

C-2p (009-0)

C-3a (009-5)

C-3p (009-0)

Arm Description

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

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

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

Part B, Arm 1 (Inhaled placebo)

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

Part B, Arm 2 (Inhaled placebo)

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

Part B, Arm 3 (Inhaled placebo)

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

Part C, Arm 1 (Inhaled placebo)

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

Part C, Arm 2 (Inhaled placebo)

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

Part C, Arm 3 (Inhaled placebo)

Outcomes

Primary Outcome Measures

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
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)]

Secondary Outcome Measures

Full Information

First Posted
December 18, 2018
Last Updated
August 28, 2019
Sponsor
Alexza Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03822364
Brief Title
Staccato Apomorphine Single and Multi Dose PK
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
November 26, 2018 (Actual)
Primary Completion Date
March 26, 2019 (Actual)
Study Completion Date
March 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexza Pharmaceuticals, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
apomorphine, aerosol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
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
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A-1 (009-1 -> active comparator)
Arm Type
Experimental
Arm Description
Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)
Arm Title
A-2 (active comparator -> 009-1)
Arm Type
Experimental
Arm Description
Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)
Arm Title
B-1a (009-2)
Arm Type
Experimental
Arm Description
Part B, Arm 1 (Inhaled apomorphine, Dose 2)
Arm Title
B-1p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part B, Arm 1 (Inhaled placebo)
Arm Title
B-2a (009-3)
Arm Type
Active Comparator
Arm Description
Part B, Arm 2 (Inhaled apomorphine, Dose 3)
Arm Title
B-2p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part B, Arm 2 (Inhaled placebo)
Arm Title
B-3a (009-4)
Arm Type
Experimental
Arm Description
Part B, Arm 3 (Inhaled apomorphine, Dose 4)
Arm Title
B-3p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part B, Arm 3 (Inhaled placebo)
Arm Title
C-1a (009-3)
Arm Type
Experimental
Arm Description
Part C, Arm 1 (Inhaled apomorphine, Dose 3)
Arm Title
C-1p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part C, Arm 1 (Inhaled placebo)
Arm Title
C-2a (009-4)
Arm Type
Experimental
Arm Description
Part C, Arm 2 (Inhaled apomorphine, Dose 4)
Arm Title
C-2p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part C, Arm 2 (Inhaled placebo)
Arm Title
C-3a (009-5)
Arm Type
Experimental
Arm Description
Part C, Arm 3 (Inhaled apomorphine, Dose 5)
Arm Title
C-3p (009-0)
Arm Type
Placebo Comparator
Arm Description
Part C, Arm 3 (Inhaled placebo)
Intervention Type
Drug
Intervention Name(s)
009-1
Intervention Description
Inhaled apomorphine via Staccato aerosol, Dose 1
Intervention Type
Drug
Intervention Name(s)
active comparator
Intervention Description
commercially available apomorphine injector
Intervention Type
Drug
Intervention Name(s)
009-0
Intervention Description
Inhaled placebo via Staccato device
Intervention Type
Drug
Intervention Name(s)
009-2
Intervention Description
Inhaled apomorphine via Staccato aerosol, Dose 2
Intervention Type
Drug
Intervention Name(s)
009-3
Intervention Description
Inhaled apomorphine via Staccato aerosol, Dose 3
Intervention Type
Drug
Intervention Name(s)
009-4
Intervention Description
Inhaled apomorphine via Staccato aerosol, Dose 4
Intervention Type
Drug
Intervention Name(s)
009-5
Intervention Description
Inhaled apomorphine via Staccato aerosol, Dose 5
Primary Outcome Measure Information:
Title
A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration
Description
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
Time Frame
24 hours
Title
B-Dose Proportionality by Power Analysis of AUCinf
Description
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)]
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geert J Groeneveld, MD, PhD
Organizational Affiliation
Center for Human Drug Research (The Netherlands)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Human Drug Research
City
Leiden
ZIP/Postal Code
2333 CL
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Staccato Apomorphine Single and Multi Dose PK

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