ADASUVE 2-dose Thorough QT/QTc Study

Alexza Pharmaceuticals

Status and phase: Completed; Phase 4

Conditions: Healthy Volunteers

Treatments: Drug: Oral placebo; Drug: ADASUVE 10 mg 2 doses 2 hours apart; Drug: Inhaled Placebo; Drug: Oral moxifloxacin 400 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01854710

204-407 (Other Identifier)

AMDC-204-407

Details and patient eligibility

About

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.

Full 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

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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60 participants in 6 patient groups

Treatment sequence ABC

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo

Treatment sequence ACB

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo

Treatment sequence BCA

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo

Treatment sequence BAC

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo

Treatment sequence CAB

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo

Treatment sequence CBA

Other 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:

Drug: Oral moxifloxacin 400 mg

Drug: Inhaled Placebo

Drug: ADASUVE 10 mg 2 doses 2 hours apart

Drug: Oral placebo