ADASUVE 2-dose Thorough QT/QTc Study

Healthy Volunteers Clinical Trial

Official title:

Thorough QT/QTc Study of 2 Doses of ADASUVE® in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01854710
• Other study ID #: AMDC-204-407
• Secondary ID: 204-407
• Status: Completed
• Phase: Phase 4
• First received: May 8, 2013
• Last updated: September 26, 2017
• Start date: May 2013
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: Alexza Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers.

Description:

It has been shown in a pre-marketing clinical study that clinically relevant QT prolongation does not appear to be associated with a single dose of ADASUVE. The potential risk of QTc prolongation following repeat dosing is unknown. Therefore the current study will assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers.

The study hypothesis H0: Placebo-subtracted max mean dQTc > 10 msec

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

• Body mass index (BMI) =18 and =32.

• Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for a 4-day period and 2 consecutive 3-day periods.

• Subjects who speak, read, and understand English and/or Dutch and are willing and able to provide written informed consent on an IEC approved form prior to the initiation of any study procedures.

• Subjects who are in good general health prior to study participation

• Female or male participants who agree to use a medically acceptable and effective birth control method

Exclusion Criteria:

• Subjects who regularly consume large amounts of xanthine-containing substances (= 5 cups of coffee/day).

• Subjects who have taken prescription or nonprescription medication within 5 days of Visit 2.

• Subjects who have had an acute illness within the last 5 days of Visit 2.

• Subjects who have smoked tobacco within the last 30 days or who have a positive cotinine test.

• Subjects who have a history of HIV, anti-HCV or HbsAg positivity.

• Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-IV.

• Subjects who test positive for alcohol or have a positive urine drug screen.

• Subjects who have a history of allergy or intolerance to loxapine or amoxapine or history of bronchospasm following inhaled loxapine treatment.

• Subjects who have an ECG abnormality.

• Subjects who have hypotension, or hypertension.

• Subjects who have a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure, transient ischemic attack, history of convulsions or other neurological disorder.

• Subjects who have a current history of asthma, chronic obstructive lung disease, or any other lung disease associated with bronchospasm.

• Subjects who use medications to treat airways disease, such as asthma or COPD.

• Subjects who have any acute respiratory signs/symptoms (e.g., wheezing).

• Female subjects who have a positive pregnancy test at screening or at admission to any of the treatment visits, or are breastfeeding.

• Subjects who have received an investigational drug within 60 days prior to the Screening Visit.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• ADASUVE 10 mg 2 doses 2 hours apart
Inhaled loxapine 10 mg 2 doses 2 hours apart
• Inhaled Placebo
Staccato placebo via inhalation x 2 at 2 hours apart
• Oral moxifloxacin 400 mg
Oral moxifloxacin 400 mg single dose
• Oral placebo
Oral capsule identical in appearance to moxifloxacin

Locations

Country	Name	City	State
Netherlands	PRA International	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Alexza Pharmaceuticals, Inc.

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Cassella JV, Spyker DA, Yeung PP. A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers. Int J Clin Pharmacol Ther. 2015 Nov;53(11):963-71. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)	A thorough QT/QTc study may be considered to have demonstrated assay sensitivity if 1 or more of the lower 95% CI values exceeds 5 msec	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Primary	Maximum Effect of ADASUVE 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 ADASUVE treatment at 12 post-inhalation times.	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Secondary	QTc Versus Loxapine Concentration	QTc @ Cmax based on linear and nonlinear regression of QTcI versus time matched serum loxapine concentrations	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Secondary	Subjects With QTcI > 450 ms	Numbers of Subjects with QTcI > 450 ms at any time point	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Secondary	Subjects With QTcI > 480 ms	Numbers of Subjects with QTcI > 480 ms (or 500 ms) at any time point	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Secondary	Subjects With QTcI Increase > 30 ms From Baseline	Numbers of Subjects with QTcI Increase > 30 ms from Baseline at any time point	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Secondary	Subjects With QTcI Increase > 60 ms From Baseline	Numbers of Subjects with QTcI Increase > 60 ms From Baseline at any time point	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr