Staccato Prochlorperazine Thorough QT/QTc

NCT00543062 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: AMDC-001-10220 July 2007
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety of Staccato Prochlorperazine on cardiac repolarization (QTc interval duration) at 2 dose levels compared to placebo in healthy volunteers.

Conditions

Cardiotoxicity

Keywords

Inhaled prochlorperazine, Thorough Qt/QTc,

Outcome Measures

Primary Outcomes (1)

• Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo

  Time-matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time-matched placebo subtraction for treatment at 11 post-inhalation times.

  1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr

Secondary Outcomes (5)

• QTcI Versus Prochlorperazine Concentration

  1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr

• Numbers and % of Subjects With QTcI > 450 ms

  24 hours

• Numbers and % of Subjects With QTcI > 480 ms

  1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr

• Numbers and % of Subjects With QTcI Change > 30 ms

  1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr

• Numbers and % of Subjects With QTcI Change > 60 ms

  1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr

Other Outcomes (1)

• Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)

  1, 1.5, 2, 2.5, 3, 5 hours

Study Arms (4)

Treatment Sequence ABCD

OTHER

Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg

Drug: Inhaled placebo; Drug: Oral placebo; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Oral moxifloxacin

Treatment Sequence BDAC

OTHER

Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg

Drug: Inhaled placebo; Drug: Oral placebo; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Oral moxifloxacin

Treatment Sequence CABD

OTHER

Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg

Drug: Inhaled placebo; Drug: Oral placebo; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Oral moxifloxacin

Treatment Sequence DCBA

OTHER

Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg

Drug: Inhaled placebo; Drug: Oral placebo; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Oral moxifloxacin

Interventions

Inhaled placebo DRUG

Inhaled Staccato placebo (0 mg)

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CABD; Treatment Sequence DCBA

Oral placebo DRUG

Oral placebo (identical to 400 mg moxifloxacin)

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CABD; Treatment Sequence DCBA

Inhaled prochlorperazine 5 mg DRUG

Staccato prochlorperazine 5 mg, single dose

Also known as: ADASUVE

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CABD; Treatment Sequence DCBA

Inhaled prochlorperazine 10 mg DRUG

Inhaled prochlorperazine 10 mg, single dose

Also known as: ADASUVE

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CABD; Treatment Sequence DCBA

Oral moxifloxacin DRUG

Oral moxifloxacin 400 mg, si/ngle dose

Treatment Sequence ABCD; Treatment Sequence BDAC; Treatment Sequence CABD; Treatment Sequence DCBA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects between the ages of 18 to 65 years, inclusive.
• Body mass index (BMI) ≥21 and ≤30.
• Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for a 3-day period and 3 consecutive 2-day periods.
• 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 in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.
• Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study.

You may not qualify if:

• Subjects who regularly consume large amounts of xanthine-containing substances must be excluded.
• Subjects who have taken prescription or nonprescription medication within 5 days of Treatment Period 1 must be excluded.
• Subjects who have had an acute illness within the last 5 days of Treatment Period 1 must be excluded.
• Subjects who have smoked tobacco within the last year must be excluded.
• Subjects who have a history of HIV positivity must be excluded.
• Subjects who have a history of allergy or intolerance to prochlorperazine or phenothiazines must be excluded.
• Subjects who have a history of contraindication to anticholinergics must be excluded.
• Subjects who have a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome must be excluded.
• Subjects who have an ECG abnormality must be excluded.
• Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.
• Subjects who have a history of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, transient ischemic attack, or pheochromocytoma must be excluded.
• Subjects who have a history of asthma or chronic obstructive lung disease must be excluded.
• Subjects who have hypotension (systolic ≤90 mmHg, diastolic ≤50 mmHg), or hypertension (systolic ≥140 mmHg, diastolic blood pressure ≥90 mmHg) must be excluded.
• Subjects who test positive for alcohol or have a positive urine drug screen must be excluded.
• Female subjects who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit Inc.

Evansville, Indiana, 47714, United States

Location

MeSH Terms

Conditions

Cardiotoxicity

Interventions

Loxapine; Moxifloxacin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Limitations and Caveats

The use of healthy subjects precludes observation of drug-induced QTc prolongation in a population with additional factors predisposing to TdP. Subjects with respiratory disease were excluded.

Results Point of Contact

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

ClinicalTrialsInfo@alexza.com

650.944.7071

Study Officials

• Randall R Stoltz, MD

  Covance GFI Research, 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
• Masking Details: This was a double-blind, double dummy, placebo controlled, randomized 4-period crossover study to assess the effects of single doses of 5 and 10 mg of Staccato Prochlorperazine on QT intervals.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Female and male subjects in approximately equal numbers were randomly assigned (1:1:1:1) to receive the 4 treatment sequences

Study Record Dates

• First Submitted: October 10, 2007
• First Posted: October 12, 2007
• Study Start: October 1, 2007
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: March 11, 2019
• Results First Posted: March 11, 2019

Record last verified: 2008-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)