Staccato Loxapine in Agitation (Proof of Concept)

NCT00369577 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: AMDC-004-201004-201
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess efficacy and safety of Staccato Loxapine in the treatment of acute agitation in schizophrenic patients. The study will be conducted in 120 agitated schizophrenic patients - either newly admitted to a hospital setting or a research unit for acute agitation or already in hospital for chronic underlying conditions. Patients meeting entry criteria will be randomized to one of two doses of Staccato Loxapine or to Staccato Placebo. Following administration of study drug, assessment of agitation state will be conducted at serial time points using standard agitation scales over a 24 hour period.

Conditions

Schizophrenia

Keywords

Agitation; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• PANSS-EC Change From Baseline

  The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (min) to 7 (max). The PANSS-EC, the sum of these 5 subscales, thus ranges from 5 to 35. Individuals were eligible if they had a PANSS-EC of ≥14 (out of 35) and a score ≥4 (out of 7) on at least 1 of the 5 items.

  2 hours

Secondary Outcomes (3)

• BARS Change From Baseline After Drug Treatment

  2 hours

• Clinical Global Impressions-Improvement Scale (CGI-I) After Drug Administration

  2 hours

• CGI-I Responders

  2 hours

Study Arms (3)

Inhaled Placebo

PLACEBO COMPARATOR

Inhaled Staccato Placebo, single dose

Drug: Inhaled Placebo

Inhaled Loxapine 5 mg

EXPERIMENTAL

Inhaled Staccato Loxapine 5 mg, single dose

Drug: Inhaled Loxapine 5 mg

Inhaled Loxapine 10 mg

EXPERIMENTAL

Inhaled Staccato Loxapine 10 mg, single dose

Drug: Inhaled Loxapine 10 mg

Interventions

Inhaled Placebo DRUG

Inhaled Placebo, single dose

Also known as: Staccato Loxapine Placebo

Inhaled Placebo

Inhaled Loxapine 5 mg DRUG

Inhaled Staccato Loxapine 5 mg, single dose

Also known as: Inhaled Staccato Loxapine 5 mg, ADASUVE 5 mg

Inhaled Loxapine 5 mg

Inhaled Loxapine 10 mg DRUG

Inhaled Staccato Loxapine 10 mg, single dose

Also known as: Inhaled Staccato Loxapine 10 mg, ADASUVE 10 mg

Inhaled Loxapine 10 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients between the ages of 18 to 65 years, inclusive.
• Patients who have met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder.
• Patients who are judged to be clinically agitated at Baseline with a total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility, uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC).
• Patients who have a value of ≥ 4 (out of 7) on at least 1 of the 5 items on the PANSS Excited Component.
• Patients who read and understand English and provide written informed consent.
• Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis and in the opinion of the Principal Investigator.
• Female participants, if of child-bearing potential and sexually active, and male participants, if sexually active with a partner of child-bearing potential, who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization and progestin implant or injection. Prohibited methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

You may not qualify if:

• Patients with agitation caused by acute intoxication must be excluded. Positive identification of non-prescription drugs during urine screening excludes the subject.
• Patients treated with benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotics within 4 hours prior to study drug administration must be excluded.
• Patients treated with injectable depot neuroleptics within one dose interval prior to study drug administration must be excluded.
• Patients with a history of allergic reactions to loxapine or amoxapine must be excluded.
• Female patients who have a positive pregnancy test at screening or are breastfeeding must be excluded.
• Patients who have Parkinson's disease, hydrocephalus, seizure disorder, or history of significant head trauma must be excluded.
• Patients with laboratory or ECG abnormalities considered clinically significant by the investigator or qualified designee that would have clinical implications for the patient's participation in the study must be excluded.
• Patients with serious and unstable illnesses including current hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease and congestive heart failure), endocrinologic, neurologic (including stroke, transient ischemic attack, subarachnoidal bleeding, brain tumor, encephalopathy, and meningitis), or hematologic disease must be excluded.
• Patients who have a history of acute or chronic pulmonary disease that precludes administration of Staccato Loxapine (asthma, bronchitis, emphysema) must be excluded.
• Patients who have received an investigational drug within 30 days prior to the current agitation episode must be excluded.
• Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device, must be excluded.

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Pacific Clinical Research Medical Group, 1317 West Foothill Blvd, Suite 200,

Upland, California, 91786, United States

Location

Related Publications (1)

• Allen MH, Feifel D, Lesem MD, Zimbroff DL, Ross R, Munzar P, Spyker DA, Cassella JV. Efficacy and safety of loxapine for inhalation in the treatment of agitation in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Oct;72(10):1313-21. doi: 10.4088/JCP.10m06011yel.

  PMID: 21294997 RESULT

MeSH Terms

Conditions

Schizophrenia; Psychomotor Agitation

Interventions

Loxapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Because of the need to provide informed consent, the types of patients enrolled in the study may not have been representative of the most severely agitated patients who present for emergency care.

Results Point of Contact

• Title: Executive VP, Research & Development, Regulatory & Quality
• Organization: Alexza Pharmaceuticals, Inc

ClinicalTrialsInfo@alexza.com

650.944.7071

Study Officials

• Daniel Zimbroff, MD

  Pacific Clinical Research Medical Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2006
• First Posted: August 29, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: January 2, 2018
• Results First Posted: January 2, 2018

Record last verified: 2013-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)