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ADASUVE 2-dose Thorough QT/QTc Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01854710
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : October 18, 2017
Last Update Posted : October 18, 2017
Sponsor:
Information provided by (Responsible Party):
Alexza Pharmaceuticals, Inc.

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

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Study Type : Interventional  (Clinical Trial)
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)
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 2013
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin

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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin

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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin

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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin

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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin

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 Name: 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 Name: AVELOX

Drug: Oral placebo
Oral capsule identical in appearance to moxifloxacin




Primary Outcome Measures :
  1. Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo [ 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 ]
    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 [ 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 ]
    QTc @ Cmax based on linear and nonlinear regression of QTcI versus time matched serum loxapine concentrations

  2. Subjects With QTcI > 450 ms [ 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 ]
    Numbers of Subjects with QTcI > 450 ms at any time point

  3. Subjects With QTcI > 480 ms [ 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 ]
    Numbers of Subjects with QTcI > 480 ms (or 500 ms) at any time point

  4. Subjects With QTcI Increase > 30 ms From Baseline [ 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 ]
    Numbers of Subjects with QTcI Increase > 30 ms from Baseline at any time point

  5. Subjects With QTcI Increase > 60 ms From Baseline [ 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 ]
    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) [ 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 ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01854710


Locations
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Netherlands
PRA International
Zuidlaren, Netherlands
Sponsors and Collaborators
Alexza Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Teresa Nunes, MD PRA Health Sciences
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01854710    
Other Study ID Numbers: AMDC-204-407
204-407 ( Other Identifier: Alexza Pharmaceuticals, Inc )
First Posted: May 15, 2013    Key Record Dates
Results First Posted: October 18, 2017
Last Update Posted: October 18, 2017
Last Verified: July 2013
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

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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:
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Moxifloxacin
Loxapine
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents