Staccato Loxapine Single Dose PK

NCT00444028 | Completed Phase 1 Results FDA Drug

• 1 other identifier: AMDC-004-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia

Keywords

Schizophrenia, Staccato Loxapine

Outcome Measures

Primary Outcomes (6)

• Tmax

  Tmax = time from inhalation to to maximum observed loxapine concentration

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

• Half-life

  Half-life of the terminal elimination phase of loxapine concentrations

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

• ke

  elimination rate constant

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

• Clearance

  clearance (CL/F) of lozxapine

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

• Cmax

  maximum concentration of loxapine observed

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

• Dose Proportionality (AUCinf) by Power Analysis

  Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being "perfect". Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is "as good as it gets".

  predose, 0.5, 1, 2, 3, 5, 10, 30 and 45 min, 1, 2, 4, 6, 12, and 24 hours

Study Arms (5)

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

Drug: inhaled Loxapine 0.625 mg; Drug: inhaled Placebo (0 mg)

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

Drug: inhaled Loxapine 1.25 mg; Drug: inhaled Placebo (0 mg)

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

Drug: inhaled Loxapine 2.5 mg; Drug: inhaled Placebo (0 mg)

Cohort D: Inhaled Loxapine 5 mg or Placebo

EXPERIMENTAL

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

Drug: inhaled Loxapine 5 mg; Drug: inhaled Placebo (0 mg)

Cohort E: Inhaled Loxapine 10 mg or Placebo

EXPERIMENTAL

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

Drug: inhaled Loxapine 10 mg; Drug: inhaled Placebo (0 mg)

Interventions

inhaled Loxapine 0.625 mg DRUG

Single 0.625 mg (lowest) dose of inhaled loxapine

Also known as: ADASUVE

Cohort A: Inhaled Loxapine 0.625 mg or Placebo

inhaled Loxapine 1.25 mg DRUG

Single 1.25 mg (2nd) dose of inhaled loxapine

Also known as: ADASUVE

Cohort B: Inhaled Loxapine 1.25 mg or Placebo

inhaled Loxapine 2.5 mg DRUG

Single 2.5 mg (3rd) dose of inhaled loxapine

Also known as: ADASUVE

Cohort C: Inhaled Loxapine 2.5 mg or Placebo

inhaled Loxapine 5 mg DRUG

Single 5 mg (4th) dose of inhaled loxapine

Also known as: ADASUVE

Cohort D: Inhaled Loxapine 5 mg or Placebo

inhaled Loxapine 10 mg DRUG

Single 10 mg (5th) dose of inhaled loxapine

Also known as: ADASUVE

Cohort E: Inhaled Loxapine 10 mg or Placebo

inhaled Placebo (0 mg) DRUG

Single placebo dose of inhaled loxapine

Also known as: PLACEBO

Cohort A: Inhaled Loxapine 0.625 mg or Placebo; Cohort B: Inhaled Loxapine 1.25 mg or Placebo; Cohort C: Inhaled Loxapine 2.5 mg or Placebo; Cohort D: Inhaled Loxapine 5 mg or Placebo; Cohort E: Inhaled Loxapine 10 mg or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between the ages of 18 to 55 years, inclusive.
• Subjects with a body mass index (BMI) ≥21 and ≤30.
• 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.

You may not qualify if:

• 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-4.
• 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 2.
• 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).

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit Inc., d/b/a Covance GFI Research

Evansville, Indiana, 47714, United States

Location

Related Publications (1)

• Spyker DA, Munzar P, Cassella JV. Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers. J Clin Pharmacol. 2010 Feb;50(2):169-79. doi: 10.1177/0091270009347866. Epub 2009 Nov 13.

  PMID: 19915181 RESULT

MeSH Terms

Conditions

Schizophrenia

Interventions

Loxapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Absolute bioavailability was not determined because loxapine for intravenous comparator was not available comercially in the US

Results Point of Contact

• Title: Executive VP, Research & Development, Regulatory & Quality
• Organization: Alexza Pharmaceuticals, Inc

ClinicalTrialsInfo@alexza.com

650.944.7071

Study Officials

• Randall Stoltz, MD

  West Pharmaceutical Services, GFI Research Center, Evansville, IN 47714

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2007
• First Posted: March 7, 2007
• Study Start: September 1, 2005
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2007-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)