Bipolar Disorder
Conditions
Keywords
Ziprasidone, Bipolar Disorder, Metabolic Syndrome
Brief summary
The purpose of this study is to explore the impact of Ziprasidone HCl on the distribution of metabolic syndrome (MS) risk factors in a population of Bipolar patients presenting with glucose intolerance, dyslipidemia and/or elevated waist circumference associated with their current antipsychotic medication.
Detailed description
The trial was terminated prematurely on December 14, 2010, due to inability to recruit the planned number of subjects and shifting organizational priorities. The decision to terminate the trial was not based on any safety or efficacy concerns.
Interventions
Ziprasidone Hydrochloride 20 to 80 mg administered orally twice a day (40-160 mg total daily dose) for up to 1 year.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject must present at least 2 of the following risk factors of MS at screening: Elevated waist circumference: \>102 cm in men and \>88 cm in women; Elevated triglycerides (TGs): ≥1.7 mmol/L (≥150 mg/dL); Reduced HDL-Cholesterol: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; Elevated fasting glucose: ≥ 5.6 mmol/L. * According to the clinical judgment of the investigator, the risk factors for MS have developed in close temporal relationship to starting an antipsychotic medication. * Substitution to a less metabolically disruptive antipsychotic medication is considered
Exclusion criteria
* Subjects with contraindication(s) to the use of Ziprasidone according to Canadian prescribing information. * Subjects with a history of treatment resistance. * Subjects with any medical condition (e.g. pre-existing diabetes, pre-existing dyslipidemia, thyroid pathology) or taking any concomitant medication (e.g. topiramate or other weight loss-promoting agents, hypoglycemic agents, hypolipemic agents), that may confound the evaluation of the study drug. * Body mass index ≥ 40 at baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation | Week 52 or Early Termination | MS risks factors: elevated (el) waist circumference: ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); el triglycerides: ≥1.7 millimoles per liter (mmol/L) (1≥50 milligrams per deciliter \[mg/dL\]); reduced high-density lipoprotein cholesterol (HDL-C): \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; el fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and el systolic/diastolic blood pressure: systolic ≥130 millimeters of mercury (mmHg) and/or diastolic ≥85 mmHg. Responder = at least 1 less risk factor at endpoint than baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Syndrome (MS) Prevalence | Baseline through Week 52 | Percentage of participants at each visit defined as having metabolic syndrome (MS) based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. MS = 3 or more of 5 characteristics: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose. |
| Change From Baseline in the Percentage of Participants With Each Individual Metabolic Syndrome (MS) Risk Factor | Baseline through Week 52 | MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg. |
| Percentage of Participants With Individual Metabolic Syndrome (MS) Risk Factors | Baseline through Week 52 | MS risks factors = elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg. |
| Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Waist Circumference | Baseline, Week 4, Week 12, Week 52 | MS risk factor elevated waist circumference defined as ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]). |
| Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Systolic/Diastolic Blood Pressure | Baseline, Week 4, Week 12, Week 52 | MS risk factor elevated systolic/diastolic blood pressure defined as systolic blood pressure ≥130 millimeters of mercury (mm Hg) and/or diastolic blood pressure ≥85 mm Hg. |
| Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Fasting Glucose | Baseline, Week 4, Week 12, Week 52 | MS risk factor elevated fasting glucose defined as ≥5.6 millimoles per liter (mmol/L) (≥100 mg/dL). |
| Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Reduced High-density Lipoprotein Cholesterol (HDL-C) | Baseline, Week 4, Week 12, Week 52 | MS risk factor reduced HDL-C defined as \<1.03 millimoles per liter (mmol/L) (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women. |
| Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Triglycerides | Baseline, Week 4, Week 12, Week 52 | MS risk factor elevated triglycerides defined as ≥1.7 millimoles per liter (mmol/L) (1≥50 mg/dL). |
| Change From Baseline in Ten-year Coronary Heart Disease (CHD) Risk According to Framingham Scoring System | Baseline, Week 4, Week 52 | Framingham scoring system risk factors: age (risk points range: -9 to 16), cholesterol (risk points range: 0 to 13), HDL cholesterol (risk points range: -1 to 2), smoking (risk points range: 0 to 9), and systolic blood pressure (risk points range: 0 to 6); total risk points range \<0 to ≥25, higher score indicates higher 10 year risk (range \<1% to ≥30% 10 year risk). |
| Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels | Baseline, Week 52 or Early Termination | — |
| Change From Baseline in Weight | Baseline, Week 4, Week 12, Week 52 or Early Termination | — |
| Change From Baseline in Body Mass Index (BMI) | Baseline, Week 4, Week 12, Week 52 or Early Termination | Body mass index = weight in kilograms (kg) / height in meters (m)\^2 . |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline, Week 52 or Early Termination | — |
| Change From Baseline in Insulin Levels | Baseline, Week 52 or Early Termination | — |
| Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) | Baseline, Week 52 | MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg. |
| Change From Baseline in Apolipoprotein B (ApoB) Levels | Baseline, Week 52 or Early Termination | — |
| Change From Baseline in Leptin | Baseline, Week 52 or Early Termination | — |
| Change From Baseline in Physical Activity Index | Baseline, Week 28, Week 52 or Early Termination | Physical activity (exercise) score derived for each participant based on the frequency and intensity of physical activities: regular walking, recreational activity, cycling, and sporting activity. Six categories of total score: inactive (range: 0-2), occasional (range: 3-5), light (range: 6-8), moderate (range: 9-12), moderately vigorous (range: 13-20), and vigorous (≥21). Higher score = higher frequency and intensity of physical activity. |
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score | Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination | Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline in Young Mania Rating Scale (YMRS) | Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination | 11-item scale that measures the severity of manic episodes from subject reported symptoms over previous 48 hours and clinical observation during interview. Four items (irritability, speech, thought content, disruptive-aggressive behaviour) are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining 7 items (elevated mood, increased motor activity-energy, sexual interest, sleep, language-thought disorder, appearance, insight) are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). YMRS total score range = 0 to 60. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Subscale | Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination | 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 patients). Higher score = more affected. |
| Clinical Global Impression - Improvement (CGI-I) Subscale Score | Week 52 or Early Termination | 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. Higher score = more affected. |
| Change From Baseline in Drug Attitude Inventory (DAI) | Week 28, Week 52 or Early Termination | DAI, a 10-item scale to assess how the attitude of schizophrenia participants toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranged from -10 to 10, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance. Change: score at observation minus score at baseline. |
| Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) | Baseline, Week 28, Week 52 or Early Termination | 0-100 single score scale focusing exclusively on participant's level of social and occupational functioning; not directly influenced by overall severity of participant's psychological symptoms; higher score = higher level of functioning. 1 to 10 = persistent inability to maintain minimal personal hygiene; unable to function without harming self or others or without considerable external support; 91 to 100 = superior functioning in a wide range of activities. |
| Change From Baseline in EuroQoL Index (EQ-I) | Baseline, Week 28, Week 52 or Early Termination | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. |
| Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score | Baseline, Week 28, Week 52 or Early Termination | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. |
| Change From Baseline in Impact of Weight on Quality of Life-Lite Version (IWQOL-Lite) Scale | Baseline, Week 28, Week 52 or Early Termination | 31-item self report inventory to assess impact of weight on quality of life. Five subscales: physical functioning, self-esteem, sexual life, public distress, and work, with categories in each subscale scored 1 (no trouble or difficulty) to 5 (persistent trouble or difficulty). The rescaled IWQoL-Lite score is determined by the sum of scores on all 31 items and rescaling this sum to a 1 to 100 scoring with 0=the poorest and 100=the best quality of life. |
| Number of Participants With Suicidal Tendencies (Columbian-Suicide Severity Rating Scale, [C-SSRS], Mapped to C-CASA [Columbia Classification Algorithm For Suicide Assessment]) | Baseline, Week 1 through Week 52 or Early Termination | C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category. |
| Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) | Baseline, Week 4, Week 52 or Early Termination | QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTc is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds. |
Countries
Canada
Participant flow
Pre-assignment details
Twenty-seven participants were screened for the study and 13 participants were assigned to study drug and treated.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone Days 1 to 3: 40 milligrams (mg) twice daily (BID); Days 4 to 7: 60 mg BID; Days 8 to15: 80 mg BID; Day 16 to Week 52: 20-80 mg BID flexible dosing. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Study Terminated by Sponsor | 7 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ziprasidone |
|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 1 / 13 |
Outcome results
Primary
Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation
MS risks factors: elevated (el) waist circumference: ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); el triglycerides: ≥1.7 millimoles per liter (mmol/L) (1≥50 milligrams per deciliter \[mg/dL\]); reduced high-density lipoprotein cholesterol (HDL-C): \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; el fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and el systolic/diastolic blood pressure: systolic ≥130 millimeters of mercury (mmHg) and/or diastolic ≥85 mmHg. Responder = at least 1 less risk factor at endpoint than baseline.
Time frame: Week 52 or Early Termination
Population: Per protocol population: all subjects in the intent-to-treat population who remained in the study for at least 28 weeks. N = number of participants with analyzable data at observation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ziprasidone | Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation | 50.00 percentage of participants |
Secondary
Change From Baseline in Apolipoprotein B (ApoB) Levels
Time frame: Baseline, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Body Mass Index (BMI)
Body mass index = weight in kilograms (kg) / height in meters (m)\^2 .
Time frame: Baseline, Week 4, Week 12, Week 52 or Early Termination
Population: PP and ITT. Results for BMI not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Subscale
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 patients). Higher score = more affected.
Time frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF)
QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTc is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds.
Time frame: Baseline, Week 4, Week 52 or Early Termination
Population: PP and ITT; n = number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) | Baseline (n=13) | 421.0 milliseconds | Standard Deviation 12.16 |
| Ziprasidone | Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) | Week 4 (n=9) | 434.0 milliseconds | Standard Deviation 13.61 |
| Ziprasidone | Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) | Week 52 or or Early Termination (n=9) | 428.8 milliseconds | Standard Deviation 14.65 |
Secondary
Change From Baseline in Drug Attitude Inventory (DAI)
DAI, a 10-item scale to assess how the attitude of schizophrenia participants toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranged from -10 to 10, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance. Change: score at observation minus score at baseline.
Time frame: Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score
EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time frame: Baseline, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in EuroQoL Index (EQ-I)
EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time frame: Baseline, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline, Week 52 or Early Termination
Population: PP and ITT. Median was reported due to small sample size and risk of skewing. Last observation = last observation while on study drug or during the lag.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ziprasidone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline | 5.5 percent HbA1c |
| Ziprasidone | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Median change | -0.2 percent HbA1c |
Secondary
Change From Baseline in Impact of Weight on Quality of Life-Lite Version (IWQOL-Lite) Scale
31-item self report inventory to assess impact of weight on quality of life. Five subscales: physical functioning, self-esteem, sexual life, public distress, and work, with categories in each subscale scored 1 (no trouble or difficulty) to 5 (persistent trouble or difficulty). The rescaled IWQoL-Lite score is determined by the sum of scores on all 31 items and rescaling this sum to a 1 to 100 scoring with 0=the poorest and 100=the best quality of life.
Time frame: Baseline, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Fasting Glucose
MS risk factor elevated fasting glucose defined as ≥5.6 millimoles per liter (mmol/L) (≥100 mg/dL).
Time frame: Baseline, Week 4, Week 12, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Systolic/Diastolic Blood Pressure
MS risk factor elevated systolic/diastolic blood pressure defined as systolic blood pressure ≥130 millimeters of mercury (mm Hg) and/or diastolic blood pressure ≥85 mm Hg.
Time frame: Baseline, Week 4, Week 12, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Triglycerides
MS risk factor elevated triglycerides defined as ≥1.7 millimoles per liter (mmol/L) (1≥50 mg/dL).
Time frame: Baseline, Week 4, Week 12, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Waist Circumference
MS risk factor elevated waist circumference defined as ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]).
Time frame: Baseline, Week 4, Week 12, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Reduced High-density Lipoprotein Cholesterol (HDL-C)
MS risk factor reduced HDL-C defined as \<1.03 millimoles per liter (mmol/L) (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women.
Time frame: Baseline, Week 4, Week 12, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Insulin Levels
Time frame: Baseline, Week 52 or Early Termination
Population: PP and ITT. Insulin levels not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Leptin
Time frame: Baseline, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score
Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Physical Activity Index
Physical activity (exercise) score derived for each participant based on the frequency and intensity of physical activities: regular walking, recreational activity, cycling, and sporting activity. Six categories of total score: inactive (range: 0-2), occasional (range: 3-5), light (range: 6-8), moderate (range: 9-12), moderately vigorous (range: 13-20), and vigorous (≥21). Higher score = higher frequency and intensity of physical activity.
Time frame: Baseline, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS)
0-100 single score scale focusing exclusively on participant's level of social and occupational functioning; not directly influenced by overall severity of participant's psychological symptoms; higher score = higher level of functioning. 1 to 10 = persistent inability to maintain minimal personal hygiene; unable to function without harming self or others or without considerable external support; 91 to 100 = superior functioning in a wide range of activities.
Time frame: Baseline, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Ten-year Coronary Heart Disease (CHD) Risk According to Framingham Scoring System
Framingham scoring system risk factors: age (risk points range: -9 to 16), cholesterol (risk points range: 0 to 13), HDL cholesterol (risk points range: -1 to 2), smoking (risk points range: 0 to 9), and systolic blood pressure (risk points range: 0 to 6); total risk points range \<0 to ≥25, higher score indicates higher 10 year risk (range \<1% to ≥30% 10 year risk).
Time frame: Baseline, Week 4, Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in the Percentage of Participants With Each Individual Metabolic Syndrome (MS) Risk Factor
MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Time frame: Baseline through Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels
Time frame: Baseline, Week 52 or Early Termination
Population: PP and ITT. Median was reported due to small sample size and risk of skewing.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ziprasidone | Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels | Total cholesterol: Baseline | 206.0 milligrams per deciliter |
| Ziprasidone | Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels | Total cholesterol: Change at Last Observation | -20.0 milligrams per deciliter |
| Ziprasidone | Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels | LDL cholesterol: Baseline | 131.0 milligrams per deciliter |
| Ziprasidone | Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels | LDL cholesterol: Change at Last Observation | -8.0 milligrams per deciliter |
Secondary
Change From Baseline in Weight
Time frame: Baseline, Week 4, Week 12, Week 52 or Early Termination
Population: PP and ITT; n = number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Weight | Baseline (n=13) | 93.5 kilograms | Standard Deviation 23.12 |
| Ziprasidone | Change From Baseline in Weight | Value at Week 4 (n=9) | 92.9 kilograms | Standard Deviation 21.99 |
| Ziprasidone | Change From Baseline in Weight | Value at Week 12 (n=5) | 97.3 kilograms | Standard Deviation 25.37 |
| Ziprasidone | Change From Baseline in Weight | Value at Week 52 (n=10) | 87.5 kilograms | Standard Deviation 24.5 |
Secondary
Change From Baseline in Young Mania Rating Scale (YMRS)
11-item scale that measures the severity of manic episodes from subject reported symptoms over previous 48 hours and clinical observation during interview. Four items (irritability, speech, thought content, disruptive-aggressive behaviour) are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining 7 items (elevated mood, increased motor activity-energy, sexual interest, sleep, language-thought disorder, appearance, insight) are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). YMRS total score range = 0 to 60.
Time frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Clinical Global Impression - Improvement (CGI-I) Subscale 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. Higher score = more affected.
Time frame: Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS)
MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Time frame: Baseline, Week 52
Population: PP and Intent-to-treat (ITT) population; ITT population = all participants enrolled in the study who received at least 1 dose of study medication and who had baseline and at least 1 post-baseline MS measurement. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Metabolic Syndrome (MS) Prevalence
Percentage of participants at each visit defined as having metabolic syndrome (MS) based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. MS = 3 or more of 5 characteristics: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose.
Time frame: Baseline through Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Number of Participants With Suicidal Tendencies (Columbian-Suicide Severity Rating Scale, [C-SSRS], Mapped to C-CASA [Columbia Classification Algorithm For Suicide Assessment])
C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.
Time frame: Baseline, Week 1 through Week 52 or Early Termination
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.
Secondary
Percentage of Participants With Individual Metabolic Syndrome (MS) Risk Factors
MS risks factors = elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm \[men\] and ≥80 cm \[women\]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: \<1.03 mmol/L (\<40 mg/dL) in men and \<1.3 mmol/L (\<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.
Time frame: Baseline through Week 52
Population: PP and ITT. Results not reported: data not summarized due to limited enrollment and early termination of the study.