A single center, randomized study investigating 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 established Parkinson*s Disease.
- Conditions
- Parkinson's diseaseParkinson's DiseasePD
- Registration Number
- NL-OMON48728
- Lead Sponsor
- Alexza Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 56
* Healthy adult males and females between 18 and 60 years of age, inclusive at the time of signing the informed consent document.
* Female subjects, who are:
o Surgically sterile (including bilateral tubal ligation) for at least 3 months prior to screening
o Postmenopausal, defined as 1 of the following:
* Last menstrual sequence greater than 12 months prior to screening
* Last menstrual sequence greater than 6 months prior to screening and a serum follicle-stimulating hormone (FSH) concentration > 40 mIU/mL
o Of childbearing potential (i.e. do not meet the criteria outlined above); subjects must:
* Have a negative urine pregnancy test at Screening and Day -1, as verified by the study doctor prior to starting study therapy.
* Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption with one of the following methods during the study participation up until 90 days after administration of study drug:
* Oral contraceptive medications
* Intra uterine devices
* Hormonal implants
* Injectable contraceptive medications
* Double-barrier methods
* Male subjects must practice true abstinence from heterosexual contact or, during sexual contact with a pregnant female or a female of childbearing potential, agree to use a condom.;* Healthy, as determined by the responsible physician, based on a medical evaluation including history, physical examination, vital signs, electrocardiograms (ECGs) and laboratory tests assessed at the screening visit and prior to the first dose of study drug. A subject with a non-clinically significant abnormality or laboratory parameters outside the reference range may be re-screened and included if the parameter or abnormality is acceptable per protocol. ;* Body weight * 50 kg and BMI within the range of 18 to 32 kg/m2, inclusive, at screening.;* Negative urine tests for selected drugs of abuse and alcohol breath test at screening and Day -1.;* Dietary habits that fall within the range of normal, as determined by the investigator. Examples of unusual diets are liquid diets, protein-only diets, high fat-diets, or low-carbohydrate diets.;* 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. ;Main criteria for Study Part C in PD Subjects IN ADDITION to above:
Inclusion Criteria
* Subjects between the ages of 30 and 85 with a clinical diagnosis of advanced PD who experience motor fluctuation and have recognizable OFF periods.
* Classified as Hoehn & Yahr stage I-IV in the ON state and have clear, self-described motor fluctuations (confirmed by the Motor Fluctuation Questionnaire) on optimized oral l-dopa or dopamine agonist therapy.
* Negative urine tests for selected drugs of abuse. However, positive urine drug screen for prescribed medication is allowed at the discretion of the PI.
* 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.
* Any condition including the presence of laboratory abnormalities, which according to the investigator places the subject at unacceptable risk if he/she were to participate in the study.
* Any condition that according to the investigator confounds the ability to interpret data from the study such as a virus, seasonal allergy, concurrent skin rash, etc. on screening or prior to drug treatment phase that may be difficult to discern from further health status changes from an investigational product.
* History of clinically significant central nervous system (e.g., seizures), cardiac, pulmonary (e.g., asthma, COPD), metabolic, renal, hepatic, or gastrointestinal (GI) 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, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study drugs.
* Use of 5HT3 antagonists, drugs known to prolong QTc and use of antihypertensives.
* PR interval > 220 msec or QRS duration > 120 msec or QTcF interval > 450 msec for men and 470 msec for women obtained at screening visit or prior to the first dose of study drug.
* Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatinine, or total bilirubin > 1.5 upper limit of normal (ULN) at screening or prior to the first dose of study drug. These laboratory tests may be repeated once, if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the reference range, the subject may be included only if the investigator considers that the previous finding will not compromise the subject*s safety and will not interfere with the interpretation of safety data.
* Use of non-prescription medications, including herbal and dietary supplements within 5 days or 5 half-lives (whichever is longer) prior to the first dose of study drug, (The subject may take paracetamol (* 2 grams/day) or ibuprofen (* 1600 mg/day) for up to 48 hours prior to the first dose of study drug. Females may take oral contraceptives. The investigator and study team may review medication use on a case-by-case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation.
* Use of medication that is inhibitor or inducer of CYP450-3A4/5 within 3 days of dosing and during the course of the study.
* Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges within 3 days prior to administration of study drug.
* Consumption of any caffeine and/or xanthine products (i.e., coffee, tea, chocolate and caffeine containing sodas, colas, etc.) within 24 hours prior to entry to the clinical unit on Day -1.
* Donation of blood, plasma or other blood products or blood collection in excess of 470 mL within 8 weeks prior to dosing.
* Subjects with a contra-indication for domperidone as per current SPC;Main criteria for Study Part C in PD Subjects IN ADDI
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* safety, tolerability, and pharmacokinetic profile of a single dose of AZ-009<br /><br>(1 mg) compared with that of ApoGo (2 mg)<br /><br>* tolerability and safety and pharmacokinetics of single ascending doses of<br /><br>AZ-009 in healthy volunteers<br /><br>- tolerability, safety, and pharmacokinetics of AZ-009 in subjects with<br /><br>established Parkinson*s disease </p><br>
- Secondary Outcome Measures
Name Time Method <p>NA</p><br>