Staccato Prochlorperazine Thorough QT/QTc

NCT ID: NCT00543062

Last Updated: 2019-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2007-12-31

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.

Detailed Description

The planned study is a single dose, double-blind, double-dummy, active and placebo controlled, randomized, 4-period cross-over study investigating investigating 2 doses levels of Staccato Prochlorperazine, a positive control with known QT/QTc prolongation (oral moxifloxacin), and placebo.

Conditions

Cardiotoxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment Sequence ABCD

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

Group Type: OTHER

Inhaled placebo

Intervention Type: DRUG

Inhaled Staccato placebo (0 mg)

Oral placebo

Intervention Type: DRUG

Oral placebo (identical to 400 mg moxifloxacin)

Inhaled prochlorperazine 5 mg

Intervention Type: DRUG

Staccato prochlorperazine 5 mg, single dose

Inhaled prochlorperazine 10 mg

Intervention Type: DRUG

Inhaled prochlorperazine 10 mg, single dose

Oral moxifloxacin

Intervention Type: DRUG

Oral moxifloxacin 400 mg, si/ngle dose

Treatment Sequence BDAC

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

Group Type: OTHER

Inhaled placebo

Intervention Type: DRUG

Inhaled Staccato placebo (0 mg)

Oral placebo

Intervention Type: DRUG

Oral placebo (identical to 400 mg moxifloxacin)

Inhaled prochlorperazine 5 mg

Intervention Type: DRUG

Staccato prochlorperazine 5 mg, single dose

Inhaled prochlorperazine 10 mg

Intervention Type: DRUG

Inhaled prochlorperazine 10 mg, single dose

Oral moxifloxacin

Intervention Type: DRUG

Oral moxifloxacin 400 mg, si/ngle dose

Treatment Sequence CABD

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

Group Type: OTHER

Inhaled placebo

Intervention Type: DRUG

Inhaled Staccato placebo (0 mg)

Oral placebo

Intervention Type: DRUG

Oral placebo (identical to 400 mg moxifloxacin)

Inhaled prochlorperazine 5 mg

Intervention Type: DRUG

Staccato prochlorperazine 5 mg, single dose

Inhaled prochlorperazine 10 mg

Intervention Type: DRUG

Inhaled prochlorperazine 10 mg, single dose

Oral moxifloxacin

Intervention Type: DRUG

Oral moxifloxacin 400 mg, si/ngle dose

Treatment Sequence DCBA

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

Group Type: OTHER

Inhaled placebo

Intervention Type: DRUG

Inhaled Staccato placebo (0 mg)

Oral placebo

Intervention Type: DRUG

Oral placebo (identical to 400 mg moxifloxacin)

Inhaled prochlorperazine 5 mg

Intervention Type: DRUG

Staccato prochlorperazine 5 mg, single dose

Inhaled prochlorperazine 10 mg

Intervention Type: DRUG

Inhaled prochlorperazine 10 mg, single dose

Oral moxifloxacin

Intervention Type: DRUG

Oral moxifloxacin 400 mg, si/ngle dose

Interventions

Inhaled placebo

Inhaled Staccato placebo (0 mg)

Intervention Type: DRUG

Oral placebo

Oral placebo (identical to 400 mg moxifloxacin)

Intervention Type: DRUG

Inhaled prochlorperazine 5 mg

Staccato prochlorperazine 5 mg, single dose

Intervention Type: DRUG

Inhaled prochlorperazine 10 mg

Inhaled prochlorperazine 10 mg, single dose

Intervention Type: DRUG

Oral moxifloxacin

Oral moxifloxacin 400 mg, si/ngle dose

Intervention Type: DRUG

Other Intervention Names

ADASUVE; ADASUVE

Eligibility Criteria

Inclusion Criteria

1. Male and female subjects between the ages of 18 to 65 years, inclusive.

2. Body mass index (BMI) ≥21 and ≤30.

3. 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.

4. 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.

5. 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.

6. 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.

Exclusion Criteria

1. Subjects who regularly consume large amounts of xanthine-containing substances must be excluded.

2. Subjects who have taken prescription or nonprescription medication within 5 days of Treatment Period 1 must be excluded.

3. Subjects who have had an acute illness within the last 5 days of Treatment Period 1 must be excluded.

4. Subjects who have smoked tobacco within the last year must be excluded.

5. Subjects who have a history of HIV positivity must be excluded.

6. Subjects who have a history of allergy or intolerance to prochlorperazine or phenothiazines must be excluded.

7. Subjects who have a history of contraindication to anticholinergics must be excluded.

8. Subjects who have a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome must be excluded.

9. Subjects who have an ECG abnormality must be excluded.

10. 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.

11. 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.

12. Subjects who have a history of asthma or chronic obstructive lung disease must be excluded.

13. Subjects who have hypotension (systolic ≤90 mmHg, diastolic ≤50 mmHg), or hypertension (systolic ≥140 mmHg, diastolic blood pressure ≥90 mmHg) must be excluded.

14. Subjects who test positive for alcohol or have a positive urine drug screen must be excluded.

15. Female subjects who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.

16. Subjects who have received an investigational drug within 30 days prior to the Screening Visit must be excluded.

17. Subjects who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving prochlorperazine, or unable to use the inhalation device, must be excluded.

18. Subjects who have any other disease(s), by history, physical examination, or laboratory abnormalities (ALT or AST > 2-fold the upper limit of normal, bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL) or that in the investigator's opinion present undue risk to the subject or may confound the interpretation of study results must be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alexza Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Randall R Stoltz, MD

Role: PRINCIPAL_INVESTIGATOR

Covance GFI Research, Evansville, IN 47714

Locations

Covance Clinical Research Unit Inc.

Evansville, Indiana, United States

Countries

United States

Other Identifiers

20 July 2007

Identifier Type: -

Identifier Source: secondary_id

AMDC-001-102

Identifier Type: -

Identifier Source: org_study_id