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

NCT04157933 | Completed Phase 1 FDA Drug

• 1 other identifier: AMDC-009-102
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (6)

A-1a

EXPERIMENTAL

Part A, Arm 1 (active), Dose 1 (009-A1)

Drug: 009-A1

A-2a

EXPERIMENTAL

Part A, Arm 2 (active), Dose 2 (009-A2)

Drug: 009-A2

A-3a

EXPERIMENTAL

Part A, Arm 3 (active), Dose 3 (009-A3)

Drug: 009-A3

A-0p

PLACEBO COMPARATOR

Part A, placebo comparator in all 3 arms, placebo dose (009-A0)

Drug: 009-A0

B-1 (009-B3 -> 009-B0)

EXPERIMENTAL

Crossover (active to placebo)

Drug: 009-B1 (active --> placebo) crossover

B-1 (009-B0 -> 009-B3)

EXPERIMENTAL

Crossover (placebo to active)

Drug: 009-B2 (placebo --> active) crossover

Interventions

009-A1 DRUG

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

A-1a

009-A2 DRUG

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

A-2a

009-A3 DRUG

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

A-3a

009-A0 DRUG

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

A-0p

009-B1 (active --> placebo) crossover DRUG

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

B-1 (009-B3 -> 009-B0)

009-B2 (placebo --> active) crossover DRUG

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

B-1 (009-B0 -> 009-B3)

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333, Netherlands

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Crossing Over, Genetic

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Homologous Recombination; Recombination, Genetic; Genetic Phenomena

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: 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 Record Dates

• First Submitted: November 1, 2019
• First Posted: November 8, 2019
• Study Start: October 16, 2019
• Primary Completion: February 28, 2020
• Study Completion: March 6, 2020
• Last Updated: November 4, 2020

Record last verified: 2019-08

Locations

NL (1)