Study to Assess the Safety and Pharmacokinetics of ADASUVE® at Doses of 2.5, 5, or 10 mg in Children and Adolescents (10 Through 17 Years of Age) With Any Condition Warranting Chronic Use of an Antipsychotic Medication

NCT02184767 | Completed Phase 1 DMC

• 1 other identifier: TV571-CNS-10018
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to assess the pharmacokinetics of loxapine and will be using plasma concentration data obtained over 48 hours after administration of the study drug

Conditions

BiPolar

Outcome Measures

Primary Outcomes (1)

• area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t)

  48 hours

Secondary Outcomes (10)

• area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)

  48 hours

• ratio of AUC0-t to AUC0-inf (AUC0-t/AUC0-inf)

  48 hours

• maximum observed plasma drug concentration (Cmax)

  48 hours

• time to maximum observed concentration (tmax)

  48 hours

• apparent terminal elimination rate constant (Kel)

  48 hours

Study Arms (1)

ADASUVE®

EXPERIMENTAL

oral inhalation using a single-use, hand-held, inhaler; dosage determined by the investigator according the participants weight

Drug: ADASUVE®

Interventions

ADASUVE® DRUG

ADASUVE® 2.5, 5, or 10 mg

Also known as: STACCATO® Loxapine for Inhalation

ADASUVE®

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written informed consent is obtained from each patient's parent or legal guardian and written assent is obtained from each patient.
• The patient is a boy or girl 10 through 17 years of age.
• The patient is within the 2.5 to 97.5 percentile for body mass index (BMI) on the basis of age and sex and is within the following weight range, as appropriate:
• boys: more than 27 kg and 127 kg or less
• girls: more than 27 kg and 111 kg or less
• The patient has a documented history of schizophrenia, bipolar disorder, autism, or any condition for which the use of antipsychotic medication (eg, risperidone, olanzapine, aripirazole, haloperidol, etc.) is warranted and/or administered. Note: Patients currently receiving treatment for any condition must be on a stable regimen (dose and frequency) for a minimum of 28 days before administration of ADASUVE.
• The patient is in good general health as determined by a complete medical history (including psychiatric and respiratory), clinical laboratory tests (include hematology, serum chemistry, and urinalysis), physical examination, body weight, 12-lead ECG, spirometry, vital signs measurements (blood pressure \[systolic and diastolic\], heart rate, body temperature, and respiratory rate), pulse oximetry, chest auscultation, neurologic examination, suicidality assessment, and concomitant medication usage inquiry.
• Female patients who are postmenarche or sexually active must have a negative pregnancy test result, must have exclusively same sex partners or be using an acceptable method of contraception, and must agree to continued use of this method for the duration of the study and for 30 days after discontinuation of ADASUVE. Acceptable methods of contraception include abstinence or an intrauterine device (known to have a failure rate of less than 1% per year).
• The patient has negative alcohol test and urine drug screen (UDS) results. A positive UDS result with appropriate medical explanation (eg, prescribed amphetamines) may be permitted after consultation with the medical monitor. Note: The UDS will also detect the presence of tetrahydrocannabinol (THC). A positive result for THC may be permitted after discussion with the sponsor if the result is low and is consistent (eg, positive at all predose assessments). If a patient tests negative for THC at screening, the result must remain negative at check-in for the patient to be eligible for study participation.
• The patient and parent/legal guardian must be willing and able to comply with study restrictions and to remain at the investigational center for the required duration at each visit.

You may not qualify if:

• The patient has a current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis, chronic bronchitis, emphysema, or other lung disease associated with bronchospasm.
• The patient has acute respiratory signs or symptoms (eg, wheezing)
• The patient currently has or has a known history of the following:
• cardiovascular disease (including, but not limited to, myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities)
• cerebrovascular disease
• conditions that predispose him or her to hypotension (including, but not limited to, dehydration, hypovolemia, or treatment with antihypertensive medications or other drugs that affect blood pressure or reduce heart rate)
• seizure disorder except a history of infantile febrile seizures
• The patient is pregnant or lactating.
• The patient is febrile.
• The patient has any other disease or condition that, in the investigator's or medical monitor's opinion, would present undue risk to the patient, or may confound the interpretation of study results.
• The patient has taken any of the following drugs, substances, or foods:
• any investigational drug within 30 days or 5 half-lives (whichever is longer) before administration of ADASUVE or, in the case of a new chemical entity, 3 months or 5 half-lives (whichever is longer) before administration of ADASUVE
• current use of medications to treat airway disease such as asthma or COPD
• loxapine or amoxapine within the last 30 days
• more than 21 units of alcohol per week within the past 2 years or a history of alcohol, narcotic, or any other substance abuse or dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR, American Psychiatric Association 2000). Note: A unit of alcohol is equal to 1 ounce of hard liquor, 5 ounces of wine, or 8 ounces of beer.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (2)

Teva Investigational Site 12468

Atlanta, Georgia, United States

Location

Teva Investigational Site 12469

Cincinnati, Ohio, United States

Location

Related Publications (1)

• Dong M, Fukuda T, Selim S, Smith MA, Rabinovich-Guilatt L, Cassella JV, Vinks AA. Clinical Trial Simulations and Pharmacometric Analysis in Pediatrics: Application to Inhaled Loxapine in Children and Adolescents. Clin Pharmacokinet. 2017 Oct;56(10):1207-1217. doi: 10.1007/s40262-017-0512-x.

  PMID: 28205038 DERIVED

MeSH Terms

Interventions

Loxapine; Inhalation

Intervention Hierarchy (Ancestors)

Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Sponsor Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: July 9, 2014
• Study Start: July 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 12, 2021

Record last verified: 2021-11

Locations

US (2)