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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 15, 2020

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

Interventions

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

Arms, Groups and Cohorts

  • Experimental: A-1a
    • Part A, Arm 1 (active), Dose 1 (009-A1)
  • Experimental: A-2a
    • Part A, Arm 2 (active), Dose 2 (009-A2)
  • Experimental: A-3a
    • Part A, Arm 3 (active), Dose 3 (009-A3)
  • Placebo Comparator: A-0p
    • Part A, placebo comparator in all 3 arms, placebo dose (009-A0)
  • Experimental: B-1 (009-B3 -> 009-B0)
    • Crossover (active to placebo)
  • Experimental: B-1 (009-B0 -> 009-B3)
    • Crossover (placebo to active)

Clinical Trial Outcome Measures

Primary Measures

  • A – Dose Proportionality of multi-dose inhaled apomorphine by Power Analysis of AUC
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 30 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Alexza Pharmaceuticals, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Geert J Groeneveld, MD, PhD, Principal Investigator, Center for Human Drug Research (The Netherlands)

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