ADASUVE 2-dose Thorough QT/QTc Study

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01854710
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 6
• Duration (Months): 2
• Patients Per Site Per Month: 29.9

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Drug: Inhaled Placebo; Drug: Oral moxifloxacin 400 mg; Drug: Oral placebo	Phase 4

Detailed 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

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Single-center, randomized, double-blind, double-dummy, 2-dose, 3-period, active- and placebo-controlled, crossover QT/QTc and pharmacokinetic (PK) study of ADASUVE in healthy volunteers. All dosing and treatment-day follow-up in the study was conducted in the clinical research unit (CRU)Single-center, randomized, double-blind, double-dummy, 2-dose, 3-period, active- and placebo-controlled, crossover QT/QTc and pharmacokinetic (PK) study of ADASUVE in healthy volunteers. All dosing and treatment-day follow-up in the study was conducted in the clinical research unit (CRU)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Thorough QT/QTc Study of 2 Doses of ADASUVE® in Healthy Volunteers
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment sequence ABC Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin
Other: Treatment sequence ACB Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin
Other: Treatment sequence BCA Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin
Other: Treatment sequence BAC Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin
Other: Treatment sequence CAB Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin
Other: Treatment sequence CBA Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Drug: ADASUVE 10 mg 2 doses 2 hours apart; Inhaled loxapine 10 mg 2 doses 2 hours apart; Other Names: Staccato Loxapine ; Drug: Inhaled Placebo; Staccato placebo via inhalation x 2 at 2 hours apart; Drug: Oral moxifloxacin 400 mg; Oral moxifloxacin 400 mg single dose; Other Names: AVELOX ; Drug: Oral placebo; Oral capsule identical in appearance to moxifloxacin

Outcome Measures

Primary Outcome Measures

1. Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   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.

Secondary Outcome Measures

1. QTc Versus Loxapine Concentration [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   QTc @ Cmax based on linear and nonlinear regression of QTcI versus time matched serum loxapine concentrations

2. Subjects With QTcI > 450 ms [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   Numbers of Subjects with QTcI > 450 ms at any time point

3. Subjects With QTcI > 480 ms [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   Numbers of Subjects with QTcI > 480 ms (or 500 ms) at any time point

4. Subjects With QTcI Increase > 30 ms From Baseline [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   Numbers of Subjects with QTcI Increase > 30 ms from Baseline at any time point

5. Subjects With QTcI Increase > 60 ms From Baseline [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   Numbers of Subjects with QTcI Increase > 60 ms From Baseline at any time point

Other Outcome Measures

1. Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity) [Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA International	Zuidlaren		Netherlands

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Teresa Nunes, MD, PRA Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01854710
• Other Study ID Numbers: AMDC-204-407; 204-407
• First Posted: May 15, 2013
• Last Update Posted: Oct 18, 2017
• Last Verified: Jul 1, 2013

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Alexza Pharmaceuticals, Inc.: ADASUVE; inhaled loxapine; thorough QT/QTc study
• Additional relevant MeSH terms: Moxifloxacin; Loxapine

Study Results

Participant Flow

Arm/Group Title	Treatment Sequence ABC	Treatment Sequence ACB	Treatment Sequence BCA	Treatment Sequence BAC	Treatment Sequence CAB	Treatment Sequence CBA
Arm/Group Description	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo	Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
Period Title: Overall Study
STARTED	10	10	10	10	10	10
COMPLETED	6	7	8	8	8	8
NOT COMPLETED	4	3	2	2	2	2

Baseline Characteristics

Arm/Group Title	All Subjects Treated
Arm/Group Description	All 6 treatment sequences = Safety Population
Overall Participants	60
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	60 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.8 (14.89)
Sex: Female, Male (Count of Participants)
Female	29 48.3%
Male	31 51.7%
Region of Enrollment (participants) [Number]
Netherlands	60 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
Description	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.
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between Adasuve and placebo exposures per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	ADASUVE-Placebo Crossover Subjects
Arm/Group Description	All subjects who completed both treatments A and B: Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo. The analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
Measure Participants	44
Least Squares Mean (95% Confidence Interval) [msec]	4.04

2. Secondary Outcome

Title	QTc Versus Loxapine Concentration
Description	QTc @ Cmax based on linear and nonlinear regression of QTcI versus time matched serum loxapine concentrations
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between Adasuve and placebo exposures per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	ADASUVE 10 mg x 2 Doses
Arm/Group Description	ADASUVE QTcI, Differences from Placebo in Change from Pre-dose Baseline and One-sided 95% Upper Confidence Bound (msec) QTcI associated with mean Cmax
Measure Participants	44
Least Squares Mean (95% Confidence Interval) [msec]	2.6

3. Secondary Outcome

Title	Subjects With QTcI > 450 ms
Description	Numbers of Subjects with QTcI > 450 ms at any time point
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- Comparisons were based on corrected differences between Adasuve and placebo (excluding moxifloxacin) exposure per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	Inhaled Placebo + Oral Placebo	ADASUVE 10 mg x 2 Doses
Arm/Group Description	Staccato Placebo 2 doses 2 hours apart + Oral Placebo Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg	ADASUVE 10 mg 2 doses 2 hours apart + Oral Placebo ADASUVE 10 mg 2 doses 2 hours apart: inhaled loxapine Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg
Measure Participants	44	44
Count of Participants [Participants]	2 3.3%	2 NaN

4. Secondary Outcome

Title	Subjects With QTcI > 480 ms
Description	Numbers of Subjects with QTcI > 480 ms (or 500 ms) at any time point
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- Comparisons were based on corrected differences between Adasuve and placebo (excluding moxifloxacin) exposure per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	Inhaled Placebo + Oral Placebo	ADASUVE 10 mg x 2 Doses
Arm/Group Description	Staccato Placebo 2 doses 2 hours apart + Oral Placebo Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg	ADASUVE 10 mg 2 doses 2 hours apart + Oral Placebo ADASUVE 10 mg 2 doses 2 hours apart: inhaled loxapine Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg
Measure Participants	44	44
Count of Participants [Participants]	0 0%	0 NaN

5. Secondary Outcome

Title	Subjects With QTcI Increase > 30 ms From Baseline
Description	Numbers of Subjects with QTcI Increase > 30 ms from Baseline at any time point
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- Comparisons were based on corrected differences between Adasuve and placebo (excluding moxifloxacin) exposure per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	Inhaled Placebo + Oral Placebo	ADASUVE 10 mg x 2 Doses
Arm/Group Description	Staccato Placebo 2 doses 2 hours apart + Oral Placebo Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg	ADASUVE 10 mg 2 doses 2 hours apart + Oral Placebo ADASUVE 10 mg 2 doses 2 hours apart: inhaled loxapine Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg
Measure Participants	44	44
Count of Participants [Participants]	0 0%	1 NaN

6. Secondary Outcome

Title	Subjects With QTcI Increase > 60 ms From Baseline
Description	Numbers of Subjects with QTcI Increase > 60 ms From Baseline at any time point
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- Comparisons were based on corrected differences between Adasuve and placebo (excluding moxifloxacin) exposure per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	Inhaled Placebo + Oral Placebo	ADASUVE 10 mg x 2 Doses
Arm/Group Description	Staccato Placebo 2 doses 2 hours apart + Oral Placebo Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg	ADASUVE 10 mg 2 doses 2 hours apart + Oral Placebo ADASUVE 10 mg 2 doses 2 hours apart: inhaled loxapine Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg
Measure Participants	44	44
Count of Participants [Participants]	0 0%	0 NaN

7. Other Pre-specified Outcome

Title	Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)
Description	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
Time Frame	Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr

Outcome Measure Data

Analysis Population Description

QT population -- LSM and CI statistics were based on the individual (within subject) corrected differences between moxifloxacin and placebo exposures per ICH Guideline E14 for a thorough QT study.

Arm/Group Title	Moxifloxacin QT Crossover Subjects
Arm/Group Description	All subjects who completed both Treatments B and C: B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo. Analyses are based on a within (paired) comparison of the time matched drug - placebo QTc values.
Measure Participants	44
Least Squares Mean (95% Confidence Interval) [msec]	10.47

Adverse Events

Time Frame	From first exposure to study treatment to 30 days after last exposure to study treatment
Adverse Event Reporting Description	Adverse events (AEs) were assessed pre-dose and at 12 prespecified time points
Arm/Group Title	Inhaled Placebo + Oral Placebo		ADASUVE 10 mg x 2 Doses		Oral Moxifloxacin
Arm/Group Description	Staccato Placebo 2 doses 2 hours apart + Oral Placebo Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg		ADASUVE 10 mg 2 doses 2 hours apart + Oral Placebo ADASUVE 10 mg 2 doses 2 hours apart: inhaled loxapine Placebo (for moxifloxacin): placebo capsule to mimic moxifloxacin 400 mg		Staccato Placebo 2 doses 2 hours apart + Oral moxifloxacin 400 mg Oral moxifloxacin 400 mg Staccato Placebo 2 doses 2 hours apart: Inhaler with no drug in it to mimic the ADASUVE inhaler
All Cause Mortality
	Inhaled Placebo + Oral Placebo		ADASUVE 10 mg x 2 Doses		Oral Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/52 (0%)		0/49 (0%)
Serious Adverse Events
	Inhaled Placebo + Oral Placebo		ADASUVE 10 mg x 2 Doses		Oral Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/52 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Inhaled Placebo + Oral Placebo		ADASUVE 10 mg x 2 Doses		Oral Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/49 (30.6%)		38/52 (73.1%)		9/49 (18.4%)
Gastrointestinal disorders
Dry mouth	0/49 (0%)	0	4/52 (7.7%)	4	0/49 (0%)	0
Dysgeusia	3/49 (6.1%)	3	8/52 (15.4%)	8	2/49 (4.1%)	2
General disorders
Fatigue	2/49 (4.1%)	2	13/52 (25%)	13	2/49 (4.1%)	2
Nervous system disorders
Dizziness	4/49 (8.2%)	4	12/52 (23.1%)	12	0/49 (0%)	0
Headache	5/49 (10.2%)	5	3/52 (5.8%)	3	2/49 (4.1%)	2
Sedation	4/49 (8.2%)	4	14/52 (26.9%)	14	2/49 (4.1%)	2
Somnolence	1/49 (2%)	1	5/52 (9.6%)	5	1/49 (2%)	1

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.