Metabolic Syndrome, Schizophrenia
Conditions
Brief summary
258 patients who have been treated for at least 3 months with oral olanzapine, risperidone or quetiapine in the treatment of schizophrenia and currently presenting with metabolic syndrome, will be randomized to: i) aripiprazole for 16 weeks, with flexible dosing within a range of 10 to 30 mg once daily (QD); or ii) continue for 16 weeks on the same atypical antipsychotic treatment prior to the study enrollment.
Interventions
DRUGAripiprazole
Tablets, Oral, 5 to 30 mg, once daily, 16 weeks
DRUGContinued Antipsychotic (Risperidone or Quetiapine or Olanzapine)
Tablets, Oral, According to summary of product characteristics (SmPC)
Sponsors
Otsuka America Pharmaceutical
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patients: * with schizophrenia being treated with olanzapine, risperidone, or quetiapine for at least 3 months * with diagnosis of metabolic syndrome * not treated for 1 of the parameters of metabolic syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (HDL) Cholesterol at Week 16 | Baseline, Week 16 | Non-HDL cholesterol was calculated as fasting Total Cholesterol minus fasting HDL Cholesterol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Fasting Lipid Parameters Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | Mean percent change from baseline in total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides. |
| Mean Change From Baseline for Fasting Glucose Levels Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | — |
| Mean Change From Baseline in Body Weight Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | — |
| Number of Participants Remaining on Metabolic Syndrome at Week 16 | Week 16 | Metabolic syndrome is defined as the presence of at least 3 out of the following Adult Treatment Panel III-A (ATP III-A) criteria (all of which are to be assessed at the same visit): waist \>102 cm in males, \>88 cm in females; blood pressure (BP) systolic BP ≥130 or diastolic BP ≥85 mm Hg; fasting HDL \<40 mg/dL in males, \<50 mg/dL in females; fasting triglycerides ≥150 mg/dL; fasting glucose ≥100 mg/dL, and/or the start of a treatment for any of the parameters of metabolic syndrome during the course of the study. |
| Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | A CGI-S assessment (a 7-point scale to evaluate the severity of symptoms) was performed at baseline (1=normal; 7=among the most extremely ill patients). A decrease in value indicates improvement. |
| Mean Change From Baseline in Subjective Well-Being Under Neuroleptics Scale (SWN-short Form) Through Week 16 | Baseline, Week 4, Week 8,Week 12, Week 16 | The SWN-short form is a 20-item self-report instrument that measures subjective well-being under neuroleptics. 10 positive and 10 negative items cover 5 health domains (subscales) (4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). With negative item scores being reversed, Subscale scores range from 4 to 24 and Total score ranges from 20 to 120. |
| Mean Change From Baseline in the Impact of Weight on Quality of Life (IWQoL-Lite) Scale Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | IWQoL-Lite is a 31-item self-report inventory to assess the impact of weight on quality of life among patients with obesity. Subscales include: Physical Function, Self Esteem, Sexual Life, Public Distress and Work. The rescaled IWQoL-Lite Total Score is determined by the sum of the 1 to 5 scores on all 31 items and rescaling this sum to a 0-100 scoring with 0=the poorest and 100=the best quality of life. A change of 7.8 to 12.0 points on the rescaled IWQoL-Lite Total Score=a meaningful improvement. A change of -4.5 to -7.6 on the rescaled IWQoL-Lite Total Score=a meaningful deterioration. |
| Median Change From Baseline in Body Mass Index (BMI) Through Week 16 | Baseline, Week 4, Week 8, Week 12, Week 16 | — |
Countries
Belgium, Czechia, France, Germany, Greece, Hungary, Spain, Switzerland, Turkey (Türkiye)
Participant flow
Pre-assignment details
125 participants were enrolled in this study; 73 were considered baseline failures and were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Control Group Olanzapine 5 mg and 10 mg, risperidone 1 mg and 4 mg, and quetiapine 100 mg and 200 mg oral tablets. Participants entered the study at the same dose as prior to randomization. Dose adjustments during the study were allowed within the dose range specified in the respective Summaries of Product Characteristics (SmPCs), according the investigator's judgment. Participants were treated for 16 weeks. | 26 |
| Aripiprazole Aripiprazole 5 mg, 10 mg, and 15 mg tablets: 5 mg once daily (QD) orally during the first week; 10 mg QD orally during the second week. Dosing was adjusted in 5 mg increments every 7 days within a range of 10 to 30 mg daily. Participants were treated for 16 weeks. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other known cause | 0 | 1 |
| Overall Study | Subject no longer met study criteria | 0 | 1 |
| Overall Study | Subject Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Aripiprazole | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 11.16 | 40.7 years STANDARD_DEVIATION 10.47 | 42.3 years STANDARD_DEVIATION 10.84 |
| Body Mass Index (BMI) | 31.31 kg/m2 | 31.45 kg/m2 | 31.38 kg/m2 |
| Body Mass Index (BMI) category < 30 kg/m2 | 13 Participants | 7 Participants | 20 Participants |
| Body Mass Index (BMI) category >=30 kg/m2 | 13 Participants | 19 Participants | 32 Participants |
| Fasting Non-High Density Lipoprotein (HDL) Cholesterol | 169.0 mg/dL | 173.1 mg/dL | 171.0 mg/dL |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black/African American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 26 participants | 23 participants | 49 participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
| Waist Circumference | 107.1 cm | 107.1 cm | 107.1 cm |
| Waist Circumference Category ≤ 102 cm for Men/ ≤ 88 cm for Women | 2 participants | 1 participants | 3 participants |
| Waist Circumference Category > 102 cm for Men/ > 88 cm for Women | 24 participants | 25 participants | 49 participants |
| Weight | 91.6 kg STANDARD_DEVIATION 18.83 | 89.1 kg STANDARD_DEVIATION 15.06 | 90.3 kg STANDARD_DEVIATION 16.93 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 2 / 26 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 |
Outcome results
Primary
Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (HDL) Cholesterol at Week 16
Non-HDL cholesterol was calculated as fasting Total Cholesterol minus fasting HDL Cholesterol.
Time frame: Baseline, Week 16
Population: Last Observation Carried Forward (LOCF) data set, Non-HDL measurements obtained after start of a treatment with a lipid-lowering agent were excluded; last measurement prior was used for LOCF analyses. Baseline data was carried forward for LOCF analysis for subjects for whom no on-treatment measurements for fasting non-HDL cholesterol was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (HDL) Cholesterol at Week 16 | 10.06 percent change | Standard Error 4.35 |
| Aripiprazole | Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (HDL) Cholesterol at Week 16 | -2.3 percent change | Standard Error 3.85 |
Comparison: Null hypothesis: no difference in mean percent change from baseline in fasting non-HDLC between aripiprazole and the control group at Week 1695% CI: [-19.14, -2.66]ANCOVA
Secondary
Mean Change From Baseline for Fasting Glucose Levels Through Week 16
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Mean Change From Baseline in Body Weight Through Week 16
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Through Week 16
A CGI-S assessment (a 7-point scale to evaluate the severity of symptoms) was performed at baseline (1=normal; 7=among the most extremely ill patients). A decrease in value indicates improvement.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Mean Change From Baseline in Subjective Well-Being Under Neuroleptics Scale (SWN-short Form) Through Week 16
The SWN-short form is a 20-item self-report instrument that measures subjective well-being under neuroleptics. 10 positive and 10 negative items cover 5 health domains (subscales) (4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). With negative item scores being reversed, Subscale scores range from 4 to 24 and Total score ranges from 20 to 120.
Time frame: Baseline, Week 4, Week 8,Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Mean Change From Baseline in the Impact of Weight on Quality of Life (IWQoL-Lite) Scale Through Week 16
IWQoL-Lite is a 31-item self-report inventory to assess the impact of weight on quality of life among patients with obesity. Subscales include: Physical Function, Self Esteem, Sexual Life, Public Distress and Work. The rescaled IWQoL-Lite Total Score is determined by the sum of the 1 to 5 scores on all 31 items and rescaling this sum to a 0-100 scoring with 0=the poorest and 100=the best quality of life. A change of 7.8 to 12.0 points on the rescaled IWQoL-Lite Total Score=a meaningful improvement. A change of -4.5 to -7.6 on the rescaled IWQoL-Lite Total Score=a meaningful deterioration.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Mean Percent Change From Baseline in Fasting Lipid Parameters Through Week 16
Mean percent change from baseline in total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Median Change From Baseline in Body Mass Index (BMI) Through Week 16
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: This measure was not analyzed because the study was terminated early and there were insufficient data to draw meaningful conclusions.
Secondary
Number of Participants Remaining on Metabolic Syndrome at Week 16
Metabolic syndrome is defined as the presence of at least 3 out of the following Adult Treatment Panel III-A (ATP III-A) criteria (all of which are to be assessed at the same visit): waist \>102 cm in males, \>88 cm in females; blood pressure (BP) systolic BP ≥130 or diastolic BP ≥85 mm Hg; fasting HDL \<40 mg/dL in males, \<50 mg/dL in females; fasting triglycerides ≥150 mg/dL; fasting glucose ≥100 mg/dL, and/or the start of a treatment for any of the parameters of metabolic syndrome during the course of the study.
Time frame: Week 16
Population: LOCF, Safety Sample For handling missing values, the metabolic syndrome is assumed to be ongoing unless there is enough data to support the resolution of the metabolic syndrome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Number of Participants Remaining on Metabolic Syndrome at Week 16 | 22 participants |
| Aripiprazole | Number of Participants Remaining on Metabolic Syndrome at Week 16 | 16 participants |
Comparison: null hypothesis: no difference between Aripiprazole and Control Group95% CI: [0.54, 1.06]Cochran-Mantel-Haenszel