临床试验/NCT00444028

NCT00444028已完成1 期

Safety, Tolerability, and Pharmacokinetics of a Single Dose of Staccato™ Loxapine for Inhalation in Normal, Healthy Volunteers

Alexza Pharmaceuticals, Inc.1 个研究点分布在 1 个国家目标入组 50 人开始时间: 2005年9月最近更新: 2018年11月20日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Alexza Pharmaceuticals, Inc.
入组人数: 50
试验地点: 1
主要终点: Dose Proportionality (AUCinf) by Power Analysis

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single inhaled dose of (administered in 1 or 2 puffs) Staccato Loxapine in healthy volunteers.

详细描述

Safety and pharmacokinetic data obtained from 50 subjects (between the ages of 18 to 55 years) entered into this randomized, placebo-controlled study. To obtain 50 enrolled subjects, screening procedures and inclusion/exclusion criteria were evaluated for 126 subjects during a variable screening period of up to 21 days. Once enrolled, subjects were randomized to either Staccato Loxapine or Staccato placebo.

Plasma samples for pharmacokinetic analysis were collected beginning on Day 0, pre-dose and continuing for 24 hr post dose. Blood samples for the PK analysis of loxapine and its metabolites (8-OH loxapine, 7-OH loxapine and amoxapine) were obtained at time 0 (immediately before dosing), at 30 sec, 1, 2, 3, 5, 10, 30, 45 min, 1, 2, 4, 6, 12, 24 hr after dosing. Plasma concentrations of loxapine and metabolites were used to estimate the following PK parameters for loxapine and its metabolites: area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf), AUC from time 0 to time tlast, the last quantifiable concentration (AUClast), maximum observed plasma concentration (Cmax), observed time of Cmax (tmax), terminal phase elimination rate constant (ke), apparent terminal elimination half life calculated from ke (T½ ), apparent total body clearance / fraction absorbed calculated from AUCinf and dose (CL/F) (for loxapine and the metabolites where permitted by measurable concentrations).

Safety was evaluated by the incidence of adverse events, clinical laboratory testing (blood chemistry, hematology, and urinalysis), physical examination, vital signs, pulse oximetry, postural vital signs, 12-lead electrocardiogram, pulmonary function tests, continuous 12-lead Holter monitoring, sedation assessments, akathisia assessments.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Male and female subjects between the ages of 18 to 55 years, inclusive.
•Subjects with a body mass index (BMI) ≥21 and ≤
•Subjects who speak, read, and understand English and are willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures.
•Subjects who are willing and able to be confined to the Clinical Research Unit (CRU) for approximately 2 days and comply with the study schedule and study requirements.
•Subjects who are in good general health as determined by a complete medical history, physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology, and urinalysis.

排除标准

•Subjects who regularly consume large amounts of xanthine-containing substances (i.e., more than 5 cups of coffee or equivalent amounts of xanthine-containing substances per day).
•Subjects who have taken prescription or nonprescription medication (with the exception of vitamins and acetaminophen if medically necessary) within 5 days of Visit 2 (Baseline).
•Subjects who have had an acute illness within 5 days of Visit 2 (Baseline).
•Subjects who have received an investigational drug within 30 days (or within 5 half lives of the investigational drug, if >30 days) prior to Visit 2 (Baseline).
•Subjects who have smoked tobacco within the last year.
•Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-
•Subjects with a history of HIV positivity.
•Subjects with a history of allergy or intolerance to dibenzoxazepines (amoxapine and loxapine).
•Subjects with a known history of contraindications to anticholinergics (bowel obstructions, urinary retention, acute glaucoma).
•Subjects with a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome (RLS).
•Subjects who test positive for alcohol or have a positive urine drug screen at Visit 1 or Visit
•Subjects who have hypotension (systolic blood pressure ≤90 mmHg, diastolic blood pressure ≤50 mmHg), or hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg).
•Subjects who have a clinically significant ECG abnormality.
•Subjects with a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure (CHF), stroke, transient ischemic attack (TIA), or a neurological disorder.
•Subjects who have a history of pulmonary disease that precludes administration of Staccato Loxapine (asthma, bronchitis, bronchospasm, emphysema).
•Subjects who have an FEV1 less than 80% of predicted values on spirometry assessments at Visit
•Female subjects who are breastfeeding or have a positive pregnancy test at Visit 1 or Visit
•Female participants of child-bearing potential or within 1 year of menopause, and sexually active are excluded unless they use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception include abstinence, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization, and birth control pills. Unacceptable methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.
•Subjects who have any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results.

研究组 & 干预措施

Cohort A: Inhaled Loxapine 0.625 mg or Placebo

Experimental

Single 0.625 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Loxapine 0.625 mg (Drug)

Cohort A: Inhaled Loxapine 0.625 mg or Placebo

Experimental

Single 0.625 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Placebo (0 mg) (Drug)

Cohort B: Inhaled Loxapine 1.25 mg or Placebo

Experimental

Single 1.25 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Loxapine 1.25 mg (Drug)

Cohort B: Inhaled Loxapine 1.25 mg or Placebo

Experimental

Single 1.25 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Placebo (0 mg) (Drug)

Cohort C: Inhaled Loxapine 2.5 mg or Placebo

Experimental

Single 2.5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Loxapine 2.5 mg (Drug)

Cohort C: Inhaled Loxapine 2.5 mg or Placebo

Experimental

Single 2.5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Placebo (0 mg) (Drug)

Cohort D: Inhaled Loxapine 5 mg or Placebo

Experimental

Single 5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Loxapine 5 mg (Drug)

Cohort D: Inhaled Loxapine 5 mg or Placebo

Experimental

Single 5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Placebo (0 mg) (Drug)

Cohort E: Inhaled Loxapine 10 mg or Placebo

Experimental

Single 10 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Loxapine 10 mg (Drug)

Cohort E: Inhaled Loxapine 10 mg or Placebo

Experimental

Single 10 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

干预措施: inhaled Placebo (0 mg) (Drug)