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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04157933
• Other study ID #: AMDC-009-102
• Status: Completed
• Phase: Phase 1
• Start date: October 16, 2019
• Est. completion date: March 6, 2020

Study information

• Verified date: August 2019
• Source: Alexza Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: March 6, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

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
• 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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Alexza Pharmaceuticals, Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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