Bipolar I Disorder
Conditions
Keywords
Bipolar 1 disorder,, agitation,, acute,, treatment
Brief summary
Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients.
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.
Interventions
DRUGInhaled Placebo
Inhaled loxapine Placebo, may repeat after 2 hours x 2
Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2
Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2
Sponsors
Alexza Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female adult patients with bipolar 1 disorder and acute agitation
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | Baseline and 2 hours | 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. |
| CGI-I Responders | Baseline and 2 hours | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Placebo Inhaled Staccato Placebo, may repeat after 2 hours x 2
Inhaled Placebo: Inhaled loxapine Placebo, may repeat after 2 hours x 2 | 105 |
| Inhaled Loxapine 5 mg Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2
Inhaled loxapine 5 mg: Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2 | 104 |
| Inhaled Loxapine 10 mg Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2
Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 | 105 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Inhaled Loxapine 5 mg | Inhaled Loxapine 10 mg | Inhaled Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 104 Participants | 105 Participants | 105 Participants | 314 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 9.63 | 40.5 years STANDARD_DEVIATION 9.8 | 40.6 years STANDARD_DEVIATION 9.82 | 40.7 years STANDARD_DEVIATION 9.72 |
| Region of Enrollment United States | 104 participants | 105 participants | 105 participants | 314 participants |
| Sex: Female, Male Female | 57 Participants | 52 Participants | 49 Participants | 158 Participants |
| Sex: Female, Male Male | 47 Participants | 53 Participants | 56 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 104 | 0 / 105 |
| other Total, other adverse events | 26 / 105 | 35 / 104 | 31 / 105 |
| serious Total, serious adverse events | 0 / 105 | 0 / 104 | 0 / 105 |
Outcome results
Primary
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.
Time frame: Baseline and 2 hours
Population: ITT Population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Placebo | Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | -4.9 units on a scale | Standard Deviation 4.77 |
| Inhaled Loxapine 5 mg | Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | -8.1 units on a scale | Standard Deviation 4.9 |
| Inhaled Loxapine 10 mg | Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | -9.0 units on a scale | Standard Deviation 4.67 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
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)
Time frame: Baseline and 2 hours
Population: ITT Population with LOCF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Placebo | CGI-I Responders | 29 Participants |
| Inhaled Loxapine 5 mg | CGI-I Responders | 69 Participants |
| Inhaled Loxapine 10 mg | CGI-I Responders | 78 Participants |
Secondary
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.
Time frame: Baseline and 2 hours
Population: ITT Population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Placebo | Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | 3.0 units on a scale | Standard Deviation 0.99 |
| Inhaled Loxapine 5 mg | Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | 2.1 units on a scale | Standard Deviation 1.1 |
| Inhaled Loxapine 10 mg | Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | 1.9 units on a scale | Standard Deviation 1.14 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA