Clinical trial NCT03822364: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: apomorphine
aerosol
Lead sponsor: Alexza Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-30
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration
timeFrame: 24 hours
measure: B-Dose Proportionality by Power Analysis of AUCinf
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Center for Human Drug Research
Study officials:
affiliation: Center for Human Drug Research (The Netherlands)
name: Geert J Groeneveld, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: