Staccato Prochlorperazine Single Dose PK Study

• ClinicalTrials.gov Identifier: NCT00610727
• Recruitment Status: Completed
• First Posted: February 8, 2008
• Results First Posted: November 5, 2018
• Last Update Posted: October 30, 2020
• Sponsor: Alexza Pharmaceuticals, Inc.
• Collaborator: PPD
• Information provided by (Responsible Party): Alexza Pharmaceuticals, Inc.

Study Description

Brief Summary:

The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of inhaled prochlorperazine

Condition or disease	Intervention/treatment	Phase
Migraine	Drug: Prochlorperazine 0.5 mg IV over 5 sec; Drug: Inhaled prochlorperazine 0.625 mg; Drug: Inhaled prochlorperazine 1.25 mg; Drug: Inhaled prochlorperazine 2.5 mg; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Inhaled placebo; Drug: Prochlorperazine 10 mg IV over 5 sec	Phase 1

Detailed Description:

The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of a single, inhaled dose of prochlorperazine (PCZ), administered as 1 or 2 puffs in healthy young volunteers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Stage 1: open-label, single-dose stage with 3 treatment periods divided into 2 phases Stage 2: double-blind, placebo-controlled, dose-escalation treatment period
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Stage 2 was a double-blind, placebo-controlled, 4 step dose-escalation trial
• Primary Purpose: Treatment
• Official Title: Tolerability, Safety and Pharmacokinetics of a Single Dose of Staccato™ Prochlorperazine for Inhalation in Normal, Healthy Volunteers
• Study Start Date: August 2004
• Actual Primary Completion Date: October 2004
• Actual Study Completion Date: October 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: Inhaled prochlorperazine 0.625 mg vs IV; Prochlorperazine 0.5 mg IV over 5 sec crossover Inhaled prochlorperazine 0.625 mg	Drug: Prochlorperazine 0.5 mg IV over 5 sec; IV Prochlorperazine for bioavailability; Other Name: PCZ; Drug: Inhaled prochlorperazine 0.625 mg; Inhaled Staccato Prochlorperazine 0.625 mg; Other Name: PCZ; Drug: Prochlorperazine 10 mg IV over 5 sec; Prochlorperazine 10 mg IV over 5 sec for patient qualification; Other Name: PCZ
Experimental: Inhaled prochlorperazine 1.25 mg; Inhaled Staccato prochlorperazine 1.25 mg	Drug: Inhaled prochlorperazine 1.25 mg; Inhaled Staccato Prochlorperazine 1.25 mg; Other Name: PCZ
Experimental: Inhaled prochlorperazine 2.5 mg; Inhaled Staccato prochlorperazine 2.5 mg	Drug: Inhaled prochlorperazine 2.5 mg; Inhaled Staccato Prochlorperazine 2.5 mg; Other Name: PCZ
Experimental: Inhaled prochlorperazine 5 mg; Inhaled Staccato prochlorperazine 5 mg	Drug: Inhaled prochlorperazine 5 mg; InhaledStaccato Prochlorperazine 5 mg; Other Name: PCZ
Experimental: Inhaled prochlorperazine 10 mg; Inhaled Staccato prochlorperazine 10 mg	Drug: Inhaled prochlorperazine 10 mg; InhaledStaccato Prochlorperazine 10 mg; Other Name: PCZ
Placebo Comparator: inhaled Placebo; inhaled Staccato Placebo (0 mg)	Drug: Inhaled placebo; Inhaled Staccato Placebo (0 mg); Other Name: ADASUVE placebo

Outcome Measures

Primary Outcome Measures :

1. Time to Peak (Tmax) [ Time Frame: 24 hours ]
   Time from dose to peak prochlorperazine concentration

Secondary Outcome Measures :

1. Absolute Bioavailability of Inhaled Prochlorperazine [ Time Frame: 24 hours ]
   Absolute bioavailability of inhaled prochlorperazine via AUC infinity
2. Dose Proportionality of Inhaled Prochlorperazine by Power Analysis [ Time Frame: 24 hours ]
   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".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects will be male or female subjects between the ages 18 to 45 years, inclusive in good general health as determined by medical history, physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology, urinalysis and in the opinion of the Principal Investigator.

Exclusion Criteria:

• Subjects with a known history of allergy or intolerance to phenothiazines or related drugs or who have any disease, 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.

Contacts and Locations

Locations

United States, Texas

PPD Phase I Clinic

Austin, Texas, United States, 78704-7016

Sponsors and Collaborators

Alexza Pharmaceuticals, Inc.

PPD

Investigators

• Study Director: Daniel A Spyker, MD; Alexza Pharmaceuticals, Inc.

More Information

Publications:

Avram MJ, Spyker DA, Henthorn TK, Cassella JV. The pharmacokinetics and bioavailability of prochlorperazine delivered as a thermally generated aerosol in a single breath to volunteers. Clin Pharmacol Ther. 2009 Jan;85(1):71-7. doi: 10.1038/clpt.2008.184. Epub 2008 Oct 1.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00610727
• Other Study ID Numbers: AMDC-004-001; Amended September 8, 2004
• First Posted: February 8, 2008
• Results First Posted: November 5, 2018
• Last Update Posted: October 30, 2020
• Last Verified: September 2008

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexza Pharmaceuticals, Inc.:

Migraine, Prochlorperazine aerosol

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Prochlorperazine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action