Bipolar I DisorderPhase 3NCT00721955

Staccato Loxapine in Agitated Patients With Bipolar Disorder

A Phase 3 study testing Inhaled loxapine 5 mg and Inhaled loxapine 10 mg in people with Bipolar I Disorder, run by Alexza Pharmaceuticals, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Bipolar I Disorder
What is being tested?: Inhaled loxapine 5 mg and Inhaled loxapine 10 mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 314 participants
Where: 6 sitesUnited States
Study dates: Jul 2008to Oct 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female adult patients with bipolar 1 disorder and acute agitation

Who cannot join

Agitation caused primarily by acute intoxication
History of drug or alcohol dependence
Treatment with benzodiazepines or other hypnotics within 4 hours prior to study drug administration

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Atlanta Center for Medical Research
Atlanta, Georgia, 30308
FutureSearch Trials
Austin, Texas, 78756
Northwest Clinical Research Center
Bellevue, Washington, 98004
Synergy Escondido
Escondido, California, 92025
Collaborative NeuroScience Network, Inc.
Garden Grove, California, 92845
Claghorn-Lesem Research Clinic
Houston, Texas, 77008

Other trials in United States

About this study

Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Patients With Bipolar I Disorder and Acute Agitation

Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients.

Read the detailed description

This is an in-clinic, multi-center, randomized, double-blind, placebo-controlled study of 2 dose levels of Staccato Loxapine, 5 and 10 mg. Patients may receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint is the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component (also known as PEC) score, performed at 2 hours after the first dose.

Conditions: Bipolar I Disorder
Being tested: Inhaled Placebo, Inhaled loxapine 5 mg, Inhaled loxapine 10 mg
Keywords: Bipolar 1 disorder,, agitation,, acute,, treatment
Medical subject headings: Psychomotor Agitation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Inhaled PlaceboDrug
Also called Staccato Placebo
Inhaled loxapine Placebo, may repeat after 2 hours x 2
Inhaled loxapine 5 mgDrug
Also called ADASUVE 5 mg
Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2
Inhaled loxapine 10 mgDrug
Also called ADASUVE 10 mg
Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2

Study groups in NCT00721955
Study group	Role	What they receive
Inhaled Placebo	Placebo comparator	Inhaled Staccato Placebo, may repeat after 2 hours x 2 Receives: Drug: Inhaled Placebo
Inhaled Loxapine 5 mg	Experimental	Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 Receives: Drug: Inhaled loxapine 5 mg
Inhaled Loxapine 10 mg	Experimental	Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 Receives: Drug: Inhaled loxapine 10 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo
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.
Measured: Baseline and 2 hours

Secondary outcomes (2)

Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo
Clinical Global Impression- Improvement (CGI-I) scores ranged from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
Measured: Baseline and 2 hours
CGI-I Responders
Frequency of response based on the CGI-I (defined as achieving a CGI-I score of 1 or 2 at 2 hours after administration of the inhalation)
Measured: Baseline and 2 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2008Oct 2008

First posted25 Jul 2008 (estimated)
Study startJul 2008
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Bipolar I DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 314 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00721955
Sponsor's protocol ID: AMDC-004-302
Status last verified: Oct 2008
First submitted: 23 Jul 2008
Last updated: 26 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

Publications

Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord. 2012 Feb;14(1):31-40. doi: 10.1111/j.1399-5618.2011.00975.x.
PubMed 22329470
Zeller S, Zun L, Cassella JV, Spyker DA, Yeung PP. Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses. BJPsych Open. 2017 Nov 10;3(6):285-290. doi: 10.1192/bjpo.bp.117.005363. eCollection 2017 Nov.
PubMed 29163985

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bipolar I Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Patients With Bipolar I Disorder and Acute Agitation
ClinicalTrials.gov ID: NCT00721955
Acronym / sponsor ID: AMDC-004-302
Conditions: Bipolar I Disorder
Keywords: Bipolar 1 disorder,, agitation,, acute,, treatment
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 314 participants (actual)
Lead sponsor: Alexza Pharmaceuticals, Inc.
Study start: Jul 2008
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 25 Jul 2008 (estimated)
Results: Posted 29 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Inhaled Placebo	Placebo comparator	Drug: Inhaled PlaceboInhaled Staccato Placebo, may repeat after 2 hours x 2
Inhaled Loxapine 5 mg	Experimental	Drug: Inhaled loxapine 5 mgInhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2
Inhaled Loxapine 10 mg	Experimental	Drug: Inhaled loxapine 10 mgInhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Male and female adult patients with bipolar 1 disorder and acute agitation

Key exclusion criteria (3 listed)

Agitation caused primarily by acute intoxication
History of drug or alcohol dependence
Treatment with benzodiazepines or other hypnotics within 4 hours prior to study drug administration

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Inhaled PlaceboAlso: Staccato PlaceboInhaled loxapine Placebo, may repeat after 2 hours x 2	Drug	Inhaled Placebo
Inhaled loxapine 5 mgAlso: ADASUVE 5 mgInhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2	Drug	Inhaled Loxapine 5 mg
Inhaled loxapine 10 mgAlso: ADASUVE 10 mgInhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2	Drug	Inhaled Loxapine 10 mg

Primary outcome

Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo
Time frame: Baseline and 2 hours
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 secondary outcomes

Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo
Time frame: Baseline and 2 hours
CGI-I Responders
Time frame: Baseline and 2 hours

Results and safety

Results posted to the registry on 29 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Inhaled Placebo	105	105
Inhaled Loxapine 5 mg	104	104
Inhaled Loxapine 10 mg	105	103

Primary outcome: Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo

Time frame: Baseline and 2 hours. Mean (Standard Deviation). Unit: units on a scale

Measure	Inhaled Placebo n = 105	Inhaled Loxapine 5 mg n = 104	Inhaled Loxapine 10 mg n = 105
Value	-4.9 (4.77)	-8.1 (4.90)	-9.0 (4.67)

Inhaled Placebo vs Inhaled Loxapine 5 mg: p <0.0001, ANCOVA
Inhaled Placebo vs Inhaled Loxapine 10 mg: p <0.0001, ANCOVA

Population analysed: ITT Population with LOCF

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From informed consent through 30 days after last treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Inhaled Placebo	0 of 105 (0%)	26 of 105 (24.8%)	0 of 105
Inhaled Loxapine 5 mg	0 of 104 (0%)	35 of 104 (33.7%)	0 of 104
Inhaled Loxapine 10 mg	0 of 105 (0%)	31 of 105 (29.5%)	0 of 105

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22329470Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord. 2012 Feb;14(1):31-40. doi: 10.1111/j.1399-5618.2011.00975.x.
Derived from this study: PubMed 29163985Zeller S, Zun L, Cassella JV, Spyker DA, Yeung PP. Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses. BJPsych Open. 2017 Nov 10;3(6):285-290. doi: 10.1192/bjpo.bp.117.005363. eCollection 2017 Nov.
Individual participant dataSharing planned: No. IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert S Fishman, MD study director

Alexza Pharmaceuticals, Inc.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inhaled loxapine 5 mg and Inhaled loxapine 10 mg in people with Bipolar I Disorder, run by Alexza Pharmaceuticals, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo (time frame: Baseline and 2 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00721955, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.