Staccato Apomorphine Single and Multi Dose PK

Alexza Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Parkinson Disease

Treatments: Drug: 009-5; Drug: 009-0; Drug: 009-1; Drug: 009-2; Drug: 009-3; Drug: active comparator; Drug: 009-4

Study type: Interventional

Funder types: Industry

Identifiers

NCT03822364

AMDC-009-101

Details and patient eligibility

About

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.

Full 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

Enrollment: 56 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

56 participants in 14 patient groups, including a placebo group

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

Experimental group

Description:

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

Treatment:

Drug: active comparator

Drug: 009-1

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

Experimental group

Description:

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

Treatment:

Drug: active comparator

Drug: 009-1

B-1a (009-2)

Experimental group

Description:

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

Treatment:

Drug: 009-2

B-1p (009-0)

Placebo Comparator group

Description:

Part B, Arm 1 (Inhaled placebo)

Treatment:

Drug: 009-0

B-2a (009-3)

Active Comparator group

Description:

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

Treatment:

Drug: 009-3

B-2p (009-0)

Placebo Comparator group

Description:

Part B, Arm 2 (Inhaled placebo)

Treatment:

Drug: 009-0

B-3a (009-4)

Experimental group

Description:

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

Treatment:

Drug: 009-4

B-3p (009-0)

Placebo Comparator group

Description:

Part B, Arm 3 (Inhaled placebo)

Treatment:

Drug: 009-0

C-1a (009-3)

Experimental group

Description:

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

Treatment:

Drug: 009-3

C-1p (009-0)

Placebo Comparator group

Description:

Part C, Arm 1 (Inhaled placebo)

Treatment:

Drug: 009-0

C-2a (009-4)

Experimental group

Description:

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

Treatment:

Drug: 009-4

C-2p (009-0)

Placebo Comparator group

Description:

Part C, Arm 2 (Inhaled placebo)

Treatment:

Drug: 009-0

C-3a (009-5)

Experimental group

Description:

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

Treatment:

Drug: 009-5

C-3p (009-0)

Placebo Comparator group

Description:

Part C, Arm 3 (Inhaled placebo)

Treatment:

Drug: 009-0