Bipolar Disorder
Conditions
Brief summary
The purpose of this study is to determine if flexibly-dosed ziprasidone is safe and effective for the treatment of children and adolescents (ages 10-17) with bipolar I disorder (manic or mixed).
Interventions
Oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength administered BID.
Oral placebo capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength administered BID.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV criteria for Bipolar I disorder (manic or mixed); age 10 - 17 years
Exclusion criteria
* Imminent risk of suicide or homicide, as judged by the site investigator; any history of serious or unstable medical illness, including risk for QT prolongation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 | Baseline, Week 4 | YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Baseline, Week 1, 2, 3 | YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Baseline, Week 1, 2, 3, 4 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill). |
| Clinical Global Impression - Improvement (CGI-I) Score | Week 1, 2, 3, 4 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to \[\>=\] 45 kilogram \[kg\] weight and ziprasidone 60 to 80 mg/day for participants with less than \[\<\] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with \>= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with \<45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion. | 149 |
| Placebo Placebo matched to ziprasidone capsule orally twice daily up to Week 4. | 88 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 13 |
| Overall Study | Laboratory abnormality | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 1 |
| Overall Study | Other | 16 | 21 |
| Overall Study | Randomized, but not treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 2 |
Baseline characteristics
| Characteristic | Ziprasidone | Placebo | Total |
|---|---|---|---|
| Age, Customized 10 to 13 years | 74 participants | 35 participants | 109 participants |
| Age, Customized 14 to 17 years | 74 participants | 53 participants | 127 participants |
| Age, Customized >=18 years | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 65 Participants | 41 Participants | 106 Participants |
| Sex: Female, Male Male | 84 Participants | 47 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 128 / 149 | 42 / 88 |
| serious Total, serious adverse events | 6 / 149 | 7 / 88 |
Outcome results
Primary
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4
YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.
Time frame: Baseline, Week 4
Population: Intent-to-treat (ITT): all randomized participants who had baseline measurements, took at least (\>=) 1 dose of study medication (ziprasidone or placebo) and had \>=1 post-baseline visit. Here, 'n' signifies those participants who were available for this measure at given time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 | Baseline (n=143,86) | 26.2 units on a scale | Standard Deviation 6.6 |
| Ziprasidone | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 | Change at Week 4 (n=97,51) | -13.8 units on a scale | Standard Deviation 7.8 |
| Placebo | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 | Baseline (n=143,86) | 27.0 units on a scale | Standard Deviation 6.6 |
| Placebo | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 | Change at Week 4 (n=97,51) | -9.9 units on a scale | Standard Deviation 7.7 |
Comparison: Change at Week 4: Mixed effects repeated measures Analysis of Covariance (ANCOVA) model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.000595% CI: [-8.12, -2.31]ANCOVA
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill).
Time frame: Baseline, Week 1, 2, 3, 4
Population: ITT population. Here, 'n' signifies those participants who were available for this measure at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 1 (n=131,85) | -0.9 units on a scale | Standard Deviation 0.8 |
| Ziprasidone | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 3 (n=108,65) | -1.3 units on a scale | Standard Deviation 1 |
| Ziprasidone | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 2 (n=120,82) | -1.1 units on a scale | Standard Deviation 1 |
| Ziprasidone | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 4 (n=96,51) | -1.4 units on a scale | Standard Deviation 1.1 |
| Ziprasidone | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Baseline (n=143,86) | 4.5 units on a scale | Standard Deviation 0.7 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 4 (n=96,51) | -0.9 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Baseline (n=143,86) | 4.5 units on a scale | Standard Deviation 0.7 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 1 (n=131,85) | -0.5 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 2 (n=120,82) | -0.6 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 | Change at Week 3 (n=108,65) | -0.7 units on a scale | Standard Deviation 1 |
Comparison: Change at Week 1: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.000295% CI: [-0.5696, -0.1812]ANCOVA
Comparison: Change at Week 2: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: <0.000195% CI: [-0.8256, -0.2936]ANCOVA
Comparison: Change at Week 3: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: <0.000195% CI: [-1.0024, -0.3572]ANCOVA
Comparison: Change at Week 4: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.000195% CI: [-1.0342, -0.3426]ANCOVA
Secondary
Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3
YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.
Time frame: Baseline, Week 1, 2, 3
Population: ITT population. 'N' (number of participants analyzed) signifies those participants who were available for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 1 (n=131,85) | -9.3 units on a scale | Standard Deviation 7.5 |
| Ziprasidone | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 2 (n=120,81) | -11.5 units on a scale | Standard Deviation 8.7 |
| Ziprasidone | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 3 (n=108,65) | -13.0 units on a scale | Standard Deviation 8.1 |
| Placebo | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 1 (n=131,85) | -6.3 units on a scale | Standard Deviation 7.1 |
| Placebo | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 2 (n=120,81) | -8.1 units on a scale | Standard Deviation 7.9 |
| Placebo | Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 | Change at Week 3 (n=108,65) | -9.0 units on a scale | Standard Deviation 7.3 |
Comparison: Change at Week 1: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.000695% CI: [-5.1045, -1.4046]ANCOVA
Comparison: Change at Week 2: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.011795% CI: [-6.3705, -0.8009]ANCOVA
Comparison: Change at Week 3: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.p-value: 0.004795% CI: [-8.2345, -1.4985]ANCOVA
Secondary
Clinical Global Impression - Improvement (CGI-I) Score
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time frame: Week 1, 2, 3, 4
Population: ITT population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score | Week 1 (n=132,85) | 2.8 units on a scale | Standard Deviation 0.9 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score | Week 3 (n=108,65) | 2.4 units on a scale | Standard Deviation 1 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score | Week 2 (n=120,82) | 2.5 units on a scale | Standard Deviation 1.1 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score | Week 4 (n=96,51) | 2.3 units on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 4 (n=96,51) | 2.8 units on a scale | Standard Deviation 1.1 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 1 (n=132,85) | 3.4 units on a scale | Standard Deviation 0.9 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 2 (n=120,82) | 3.2 units on a scale | Standard Deviation 1.1 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 3 (n=108,65) | 3.1 units on a scale | Standard Deviation 1.3 |
Comparison: Week 4: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects was used for the analysis.p-value: 0.000495% CI: [-1.18, -0.34]ANCOVA