Trial Outcomes & Findings for Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder (NCT NCT00190749)

NCT ID: NCT00190749

Last Updated: 2010-05-04

Results Overview

Normalized insulin sensitivity index (Mffm/I) was defined as the ratio of whole body glucose disposal rate normalized to fat-free mass (Mffm) divided by the plasma insulin concentration (I) during steady-state conditions of the clamp procedure. Units:\[(mg glucose)\*min\*mL\] / \[(kg fat free body mass)\*(micro IU insulin)\]

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

130 participants

Primary outcome timeframe

baseline and 12 weeks

Results posted on

2010-05-04

Participant Flow

Study Period I was a Screening Period. Study Period II was a Inpatient Washout/Diet Stabilization Period. Study Period III (randomization) was the Double-Blind Therapy Period.

Participant milestones

Participant milestones
Measure
Olanzapine
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Overall Study
STARTED
68
62
Overall Study
COMPLETED
42
31
Overall Study
NOT COMPLETED
26
31

Reasons for withdrawal

Reasons for withdrawal
Measure
Olanzapine
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Overall Study
Lost to Follow-up
8
11
Overall Study
Withdrawal by Subject
10
6
Overall Study
Protocol Violation
5
4
Overall Study
Adverse Event
0
5
Overall Study
Lack of Efficacy
2
3
Overall Study
Reason Not Specified
0
2
Overall Study
Sponsor Decision
1
0

Baseline Characteristics

Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Olanzapine
n=68 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=62 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Total
n=130 Participants
Total of all reporting groups
Age Continuous
43.49 years
STANDARD_DEVIATION 9.45 • n=5 Participants
42.58 years
STANDARD_DEVIATION 8.98 • n=7 Participants
43.06 years
STANDARD_DEVIATION 9.20 • n=5 Participants
Sex: Female, Male
Female
23 Participants
n=5 Participants
21 Participants
n=7 Participants
44 Participants
n=5 Participants
Sex: Female, Male
Male
45 Participants
n=5 Participants
41 Participants
n=7 Participants
86 Participants
n=5 Participants
Region of Enrollment
United States
68 participants
n=5 Participants
62 participants
n=7 Participants
130 participants
n=5 Participants
Diagnosis
Schizophrenia,paranoid
40 participants
n=5 Participants
45 participants
n=7 Participants
85 participants
n=5 Participants
Diagnosis
Schizoaffective disorder
27 participants
n=5 Participants
16 participants
n=7 Participants
43 participants
n=5 Participants
Diagnosis
Schizophrenia, undifferentiated
1 participants
n=5 Participants
1 participants
n=7 Participants
2 participants
n=5 Participants
Race/Ethnicity
Caucasian
27 participants
n=5 Participants
30 participants
n=7 Participants
57 participants
n=5 Participants
Race/Ethnicity
African descent
34 participants
n=5 Participants
26 participants
n=7 Participants
60 participants
n=5 Participants
Race/Ethnicity
Hispanic
4 participants
n=5 Participants
5 participants
n=7 Participants
9 participants
n=5 Participants
Race/Ethnicity
East Asian
1 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
Race/Ethnicity
Other
2 participants
n=5 Participants
1 participants
n=7 Participants
3 participants
n=5 Participants
Brief Psychiatric Rating Scale Anxiety Depression Score-Baseline
4.46 units on a scale
STANDARD_DEVIATION 2.46 • n=5 Participants
3.74 units on a scale
STANDARD_DEVIATION 2.13 • n=7 Participants
4.12 units on a scale
STANDARD_DEVIATION 2.33 • n=5 Participants
Brief Psychiatric Rating Scale Negative Symptom Score-Baseline
2.28 units on a scale
STANDARD_DEVIATION 1.98 • n=5 Participants
1.89 units on a scale
STANDARD_DEVIATION 1.79 • n=7 Participants
2.09 units on a scale
STANDARD_DEVIATION 1.89 • n=5 Participants
Brief Psychiatric Rating Scale Positive Symptom Score-Baseline
5.40 units on a scale
STANDARD_DEVIATION 2.69 • n=5 Participants
5.47 units on a scale
STANDARD_DEVIATION 2.52 • n=7 Participants
5.43 units on a scale
STANDARD_DEVIATION 2.60 • n=5 Participants
Brief Psychiatric Rating Scale Total Score-Baseline
15.63 units on a scale
STANDARD_DEVIATION 6.06 • n=5 Participants
14.29 units on a scale
STANDARD_DEVIATION 6.00 • n=7 Participants
14.99 units on a scale
STANDARD_DEVIATION 6.04 • n=5 Participants
Clinical Global Impression Severity Score- Baseline
3.68 units on a scale
STANDARD_DEVIATION 0.56 • n=5 Participants
3.65 units on a scale
STANDARD_DEVIATION 0.52 • n=7 Participants
3.66 units on a scale
STANDARD_DEVIATION 0.54 • n=5 Participants
Extrapyramidal Scores/Abnormal Involuntary Movement-Baseline
0.42 units on a scale
STANDARD_DEVIATION 1.14 • n=5 Participants
0.47 units on a scale
STANDARD_DEVIATION 1.13 • n=7 Participants
0.44 units on a scale
STANDARD_DEVIATION 1.13 • n=5 Participants
Extrapyramidal Scores/Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment-Baseline
0.27 units on a scale
STANDARD_DEVIATION 0.66 • n=5 Participants
0.32 units on a scale
STANDARD_DEVIATION 0.67 • n=7 Participants
0.29 units on a scale
STANDARD_DEVIATION 0.67 • n=5 Participants
Extrapyramidal Scores/Simpson-Angus-Baseline
0.97 units on a scale
STANDARD_DEVIATION 1.87 • n=5 Participants
0.90 units on a scale
STANDARD_DEVIATION 1.80 • n=7 Participants
0.94 units on a scale
STANDARD_DEVIATION 1.83 • n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: N=number of patients with a baseline and post-baseline result within each treatment group for Mffm/I and weight.

Normalized insulin sensitivity index (Mffm/I) was defined as the ratio of whole body glucose disposal rate normalized to fat-free mass (Mffm) divided by the plasma insulin concentration (I) during steady-state conditions of the clamp procedure. Units:\[(mg glucose)\*min\*mL\] / \[(kg fat free body mass)\*(micro IU insulin)\]

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change in Baseline to Last Observation In Normalized Insulin Sensitivity Index at Low Insulin Phase Using Change in Weight as a Covariate
Baseline
0.1664 Mffm/I
Standard Deviation 0.1120
0.1937 Mffm/I
Standard Deviation 0.1286
Change in Baseline to Last Observation In Normalized Insulin Sensitivity Index at Low Insulin Phase Using Change in Weight as a Covariate
Change to Last Observation
-0.0149 Mffm/I
Standard Deviation 0.0786
-0.0327 Mffm/I
Standard Deviation 0.0829

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in weight

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Weight.
-0.212 correlation
-0.188 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in BMI

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Body Mass Index (BMI)
-0.182 correlation
-0.195 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in ratio of visceral far area to subcutaneous fat area

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=26 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Ratio of Visceral Fat Area to the Subcutaneous Fat Area.
-0.055 correlation
0.101 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin senstivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Brief Psychiatric Rating Scale scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Brief Psychiatric Rating Scale Scores.
0.035 correlation
0.066 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Clinical Global Impression-Severity of Illness scale scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Clinical Global Impression - Severity of Illness Scale Scores.
0.068 correlation
0.234 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Abnormal Involuntary Movement Scale scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Abnormal Involuntary Movement Scale Scores.
0.001 correlation
-0.134 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Barnes Akathisia scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlation Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Barnes Akathisia Scale Scores.
-0.120 correlation
0.006 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in the Simpson Angus Scale scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in the Simpson Angus Scale Scores.
0.184 correlation
0.249 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in waist circumference

Outcome measures

Outcome measures
Measure
Olanzapine
n=40 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=29 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Waist Circumference.
-0.206 correlation
-0.263 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in visceral fat area

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=27 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Visceral Fat Area.
-0.048 correlation
-0.057 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in subcutaneous fat area

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=27 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Subcutaneous Fat Area.
-0.043 correlation
-0.085 correlation

SECONDARY outcome

Timeframe: 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Eating Behavior Assessment Scale scores

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 1: How Hungry?
-0.137 correlation
-0.371 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 2: How Strong Appetite?
-0.137 correlation
-0.269 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 3: Craved Sweets or Other Carbohydrates?
-0.009 correlation
0.035 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 4: Craved Fatty Foods?
-0.068 correlation
-0.184 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 5: Felt Full or Satisfied After Meal?
-0.117 correlation
-0.060 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 6:Excessive Amount of Food to Feel Satisfied?
0.134 correlation
0.067 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 7: Thinking About Food?
-0.172 correlation
0.045 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 8: Overeating?
-0.032 correlation
-0.165 correlation
Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores.
Item 9: Feel Eating is Out of Control?
-0.075 correlation
-0.354 correlation

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations

Within-and Between-Treatment Group changes in Body Mass Index from baseline to last observation carried forward.

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Body Mass Index
Baseline
28.96 kilograms per square meter (kg/m2)
Standard Deviation 5.17
28.79 kilograms per square meter (kg/m2)
Standard Deviation 5.40
Change From Baseline to 12 Week Endpoint in Body Mass Index
Change to Last Observation
1.02 kilograms per square meter (kg/m2)
Standard Deviation 1.61
0.39 kilograms per square meter (kg/m2)
Standard Deviation 1.15

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Weight change from baseline to last visit (last observation carried forward)

Outcome measures

Outcome measures
Measure
Olanzapine
n=41 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=33 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Weight
Baseline
85.93 kilograms
Standard Deviation 17.26
86.55 kilograms
Standard Deviation 19.53
Change From Baseline to 12 Week Endpoint in Weight
Change to Last Observation
2.98 kilograms
Standard Deviation 4.82
1.23 kilograms
Standard Deviation 4.45

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Randomized patients who completed the baseline and endpoint clamps with both diet stabilizations.

Waist circumference change from baseline to last observation carried forward.

Outcome measures

Outcome measures
Measure
Olanzapine
n=40 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=29 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Waist Circumference
Baseline
99.13 centimeters
Standard Deviation 14.42
98.49 centimeters
Standard Deviation 11.60
Change From Baseline to 12 Week Endpoint in Waist Circumference
Change to Last Observation
2.38 centimeters
Standard Deviation 7.46
0.17 centimeters
Standard Deviation 4.99

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Abdominal CT scan of changes from baseline to last observation of randomized patients who completed baseline and endpoint clamps with both diet stabilizations

Visceral fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=27 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Visceral Fat Area
Baseline
101.46 square centimeters (cm2)
Standard Deviation 54.99
102.17 square centimeters (cm2)
Standard Deviation 52.61
Change From Baseline to 12 Week Endpoint in Visceral Fat Area
Change to Last Observation
4.70 square centimeters (cm2)
Standard Deviation 21.21
8.70 square centimeters (cm2)
Standard Deviation 42.39

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Abdominal CT scan change from baseline to last observation for randomized patients who completed baseline and endpoint clamps with both diet stabilizations

Subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=27 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Subcutaneous Fat Area
Baseline
281.07 square centimeters (cm2)
Standard Deviation 158.59
317.16 square centimeters (cm2)
Standard Deviation 172.19
Change From Baseline to 12 Week Endpoint in Subcutaneous Fat Area
Change to last observation
4.94 square centimeters (cm2)
Standard Deviation 40.36
35.15 square centimeters (cm2)
Standard Deviation 105.64

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Abdominal CT scan change from baseline to last observation of randomized patients who completed the baseline and endpoint clamps with both diet stabilizations

Ratio of the visceral fat area to the subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Outcome measures

Outcome measures
Measure
Olanzapine
n=32 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=26 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in the Ratio of the Visceral Fat Area to the Subcutaneous Fat Area
Baseline
0.41 ratio in square centimeters (cm2)
Standard Deviation 0.25
0.43 ratio in square centimeters (cm2)
Standard Deviation 0.33
Change From Baseline to 12 Week Endpoint in the Ratio of the Visceral Fat Area to the Subcutaneous Fat Area
Change to last observation
0.01 ratio in square centimeters (cm2)
Standard Deviation 0.12
0.00 ratio in square centimeters (cm2)
Standard Deviation 0.14

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: BPRS Total and Subscale Scores-Change from Baseline to Last Observation Carried Forward, all randomized patients, double-blind treatment period

Brief Psychiatric Rating Scale (BPRS) is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Item scores range from 0 (not present) to 6 (extremely severe). Total Scores range from 0 to 108; Positive Subscale Scores range from 0 to 24. Negative Subscale Scores range from 0 to 18. Anxiety-Depression Subscale Scores range from 0 to 24.

Outcome measures

Outcome measures
Measure
Olanzapine
n=60 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=56 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Negative Subscale Score Baseline
2.32 units on a scale
Standard Deviation 2.04
1.88 units on a scale
Standard Deviation 1.83
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Total Score Baseline
13.32 units on a scale
Standard Deviation 6.26
13.96 units on a scale
Standard Deviation 6.02
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Total Score Change to Last Observation
-1.98 units on a scale
Standard Deviation 6.30
-1.48 units on a scale
Standard Deviation 7.99
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Positive Subscale Score Baseline
5.22 units on a scale
Standard Deviation 2.75
5.27 units on a scale
Standard Deviation 2.51
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Positive Subscale Score Change to Last Observation
-0.82 units on a scale
Standard Deviation 2.81
-1.20 units on a scale
Standard Deviation 3.08
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Negative Subscale Score Change to Last Observation
-0.38 units on a scale
Standard Deviation 1.58
-0.02 units on a scale
Standard Deviation 1.99
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Anxiety-Depression Baseline
4.33 units on a scale
Standard Deviation 2.59
3.73 units on a scale
Standard Deviation 2.18
Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores
Anxiety-Depression Change to Last Observation
-0.78 units on a scale
Standard Deviation 2.29
-0.32 units on a scale
Standard Deviation 2.50

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.

Outcome measures

Outcome measures
Measure
Olanzapine
n=60 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=56 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Clinical Global Impression - Severity of Illness Scores
Baseline
3.65 units on a scale
Standard Deviation 0.55
3.61 units on a scale
Standard Deviation 0.53
Change From Baseline to 12 Week Endpoint in Clinical Global Impression - Severity of Illness Scores
Change to last observation
-0.22 units on a scale
Standard Deviation 0.58
-0.23 units on a scale
Standard Deviation 0.66

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

A 12-item instrument assesses observed abnormal movements in different parts of body. Seven items are scored in a 5-point scale (0 = none/normal, 4 = severe) which evaluates abnormal movements in 3 main anatomic areas (orofacial area, extremities, and trunk). Total scores range from 0 to 28. Five collected elements are not used in this total.

Outcome measures

Outcome measures
Measure
Olanzapine
n=54 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=47 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Abnormal Involuntary Movement Scale Scores
Baseline
0.48 units on a scale
Standard Deviation 1.24
0.53 units on a scale
Standard Deviation 1.25
Change From Baseline to 12 Week Endpoint in Abnormal Involuntary Movement Scale Scores
Change to last observation
0.04 units on a scale
Standard Deviation 1.15
0.04 units on a scale
Standard Deviation 1.35

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

The BARS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global clinical assessment and is rated 0 to 5 (0 = absent, 5 = severe). The other 3 items (related to objective and subjective assessments) are not used for these analyses.

Outcome measures

Outcome measures
Measure
Olanzapine
n=54 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=47 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Barnes Akathisia Rating Scale (BARS) Scores
Change to last observation
0.02 units on a scale
Standard Deviation 0.84
-0.02 units on a scale
Standard Deviation 0.82
Change From Baseline to 12 Week Endpoint in Barnes Akathisia Rating Scale (BARS) Scores
Baseline
0.24 units on a scale
Standard Deviation 0.64
0.36 units on a scale
Standard Deviation 0.70

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Measures neuroleptic-induced parkinsonism. Total score of Simpson Angus Scale consists of the sum of 10 items rated on a 5-point severity scale where 0=normal and 4=extreme. The total score ranges from 0 to 40.

Outcome measures

Outcome measures
Measure
Olanzapine
n=54 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=47 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Simpson Angus Scale Scores
Baseline
1.13 units on a scale
Standard Deviation 2.02
0.94 units on a scale
Standard Deviation 1.79
Change From Baseline to 12 Week Endpoint in Simpson Angus Scale Scores
Change to last observation
-0.06 units on a scale
Standard Deviation 1.48
0.30 units on a scale
Standard Deviation 1.92

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation carried forward, all randomized patients, double-blind treatment period

Eating Behavior Assessment Scale is a 9-item self-rated tool used to evaluate appetite and eating behaviors. Item scores range from 0 (never) to 4 (always).

Outcome measures

Outcome measures
Measure
Olanzapine
n=59 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=53 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 1 Baseline (How Hungry?)
1.42 units on a scale
Standard Deviation 1.09
1.32 units on a scale
Standard Deviation 0.94
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 1 Change to Last Observation
0.25 units on a scale
Standard Deviation 1.27
0.42 units on a scale
Standard Deviation 1.18
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 2 Baseline (How Strong Appetite?)
1.54 units on a scale
Standard Deviation 1.10
1.32 units on a scale
Standard Deviation 1.03
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 2 Change to Last Observation
0.17 units on a scale
Standard Deviation 1.26
0.38 units on a scale
Standard Deviation 1.33
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 3 Baseline (Craved Sweets or Other Carbos?)
1.00 units on a scale
Standard Deviation 1.17
0.83 units on a scale
Standard Deviation 1.10
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 3 Change to Last Observation
0.19 units on a scale
Standard Deviation 1.47
0.36 units on a scale
Standard Deviation 1.18
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 4 Baseline (Craved Fatty Foods?)
0.80 units on a scale
Standard Deviation 1.01
0.74 units on a scale
Standard Deviation 1.00
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 4 Change to Last Observation
0.31 units on a scale
Standard Deviation 1.52
0.25 units on a scale
Standard Deviation 1.05
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 5 Baseline (Felt Full After Meal?)
2.59 units on a scale
Standard Deviation 0.93
2.55 units on a scale
Standard Deviation 0.89
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 5 Change to Last Observation
-0.17 units on a scale
Standard Deviation 1.15
0.00 units on a scale
Standard Deviation 1.19
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 6 Baseline(Excessive Food to Feel Satisfied?)
0.86 units on a scale
Standard Deviation 1.21
0.79 units on a scale
Standard Deviation 1.12
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 6 Change to Last Observation
0.17 units on a scale
Standard Deviation 1.40
0.28 units on a scale
Standard Deviation 1.25
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 7 Baseline (Thinking About Food?)
0.90 units on a scale
Standard Deviation 1.18
0.77 units on a scale
Standard Deviation 1.14
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 7 Change to Last Observation
0.12 units on a scale
Standard Deviation 1.31
0.13 units on a scale
Standard Deviation 1.36
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 8 Baseline (Overeating?)
0.42 units on a scale
Standard Deviation 0.95
0.53 units on a scale
Standard Deviation 1.08
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 8 Change to Last Observation
0.17 units on a scale
Standard Deviation 1.33
0.15 units on a scale
Standard Deviation 1.31
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 9 Baseline (Feel Eating is Out of Control?)
0.10 units on a scale
Standard Deviation 0.36
0.26 units on a scale
Standard Deviation 0.76
Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores
Item 9 Change to Last Observation
0.25 units on a scale
Standard Deviation 0.94
0.11 units on a scale
Standard Deviation 1.01

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation, all randomized patients, double-blind treatment period

Fasting lipid parameters including total cholesterol, change from baseline to last observation carried forward.

Outcome measures

Outcome measures
Measure
Olanzapine
n=51 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=49 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Total Cholesterol
Baseline
4.91 millimoles per Liter (mmol/L)
Standard Deviation 1.06
4.97 millimoles per Liter (mmol/L)
Standard Deviation 1.12
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Total Cholesterol
Change to Last Observation
0.18 millimoles per Liter (mmol/L)
Standard Deviation 0.89
0.01 millimoles per Liter (mmol/L)
Standard Deviation 0.79

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation, all randomized patients, double-blind treatment period

Fasting lipid parameters including Direct LDL, change from baseline to last observation carried forward.

Outcome measures

Outcome measures
Measure
Olanzapine
n=51 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=49 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Direct Low Density Lipoprotein (LDL)
Baseline
3.18 millimoles per Liter (mmol/L)
Standard Deviation 0.90
3.11 millimoles per Liter (mmol/L)
Standard Deviation 0.99
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Direct Low Density Lipoprotein (LDL)
Change to last observation
-0.03 millimoles per Liter (mmol/L)
Standard Deviation 0.67
-0.02 millimoles per Liter (mmol/L)
Standard Deviation 0.63

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation, all randomized patients, double-blind treatment period

Fasting lipid parameters including HDL change from baseline to last observation carried forward.

Outcome measures

Outcome measures
Measure
Olanzapine
n=51 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=48 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including High Density Lipoprotein (HDL)
Baseline
1.08 millimoles per Liter (mmol/L)
Standard Deviation 0.25
1.18 millimoles per Liter (mmol/L)
Standard Deviation 0.32
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including High Density Lipoprotein (HDL)
Change to last observation
0.06 millimoles per Liter (mmol/L)
Standard Deviation 0.24
0.05 millimoles per Liter (mmol/L)
Standard Deviation 0.27

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Change from baseline to last observation, all randomized patients, double-blind treatment period

Changes in fasting lipid parameters including triglycerides last observation carried forward (LOCF) mean change from baseline

Outcome measures

Outcome measures
Measure
Olanzapine
n=51 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=49 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Triglycerides
Baseline
1.68 millimoles per Liter (mmol/L)
Standard Deviation 0.91
1.55 millimoles per Liter (mmol/L)
Standard Deviation 0.85
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Triglycerides
Change to Last Observation
0.34 millimoles per Liter (mmol/L)
Standard Deviation 1.12
-0.10 millimoles per Liter (mmol/L)
Standard Deviation 0.74

SECONDARY outcome

Timeframe: baseline and 12 weeks.

Population: Mean change from baseline, all randomized patients, double-blind treatment period

Changes in lipid parameters and subclass lipoproteins last observation carried forward (LOCF) mean change from baseline. HDL=High Density Lipoprotein, IDL=Intermdiate Density Lipoprotein, LDL=Low Density Lipoprotein, VLDL=Very Low Density Lipoprotein.

Outcome measures

Outcome measures
Measure
Olanzapine
n=40 Participants
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=32 Participants
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
HDL particles, total, baseline
28.39 nanomoles per Liter (nmol/L)
Standard Deviation 5.38
29.81 nanomoles per Liter (nmol/L)
Standard Deviation 5.29
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
HDL particles, total, change to last observation
1.71 nanomoles per Liter (nmol/L)
Standard Deviation 4.84
-1.09 nanomoles per Liter (nmol/L)
Standard Deviation 4.34
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
IDL, baseline
53.18 nanomoles per Liter (nmol/L)
Standard Deviation 55.32
52.56 nanomoles per Liter (nmol/L)
Standard Deviation 61.38
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
IDL, change to last observation
21.40 nanomoles per Liter (nmol/L)
Standard Deviation 59.63
-2.69 nanomoles per Liter (nmol/L)
Standard Deviation 46.07
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Medium small LDL, baseline
175.15 nanomoles per Liter (nmol/L)
Standard Deviation 98.59
197.00 nanomoles per Liter (nmol/L)
Standard Deviation 116.28
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Medium small LDL, change to last observation
35.70 nanomoles per Liter (nmol/L)
Standard Deviation 52.40
-11.47 nanomoles per Liter (nmol/L)
Standard Deviation 84.73
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Small LDL, baseline
878.68 nanomoles per Liter (nmol/L)
Standard Deviation 481.65
977.84 nanomoles per Liter (nmol/L)
Standard Deviation 622.99
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Small LDL, change to last observation
128.55 nanomoles per Liter (nmol/L)
Standard Deviation 236.89
-74.09 nanomoles per Liter (nmol/L)
Standard Deviation 428.13
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Very small LDL, baseline
703.63 nanomoles per Liter (nmol/L)
Standard Deviation 385.31
780.78 nanomoles per Liter (nmol/L)
Standard Deviation 508.24
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
Very small LDL, change to last observation
92.75 nanomoles per Liter (nmol/L)
Standard Deviation 193.00
-62.50 nanomoles per Liter (nmol/L)
Standard Deviation 347.08
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
VLDL mean particle size, baseline
51.21 nanomoles per Liter (nmol/L)
Standard Deviation 8.57
51.05 nanomoles per Liter (nmol/L)
Standard Deviation 11.83
Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses
VLDL mean particle size, change to last observ.
4.09 nanomoles per Liter (nmol/L)
Standard Deviation 7.83
1.80 nanomoles per Liter (nmol/L)
Standard Deviation 9.21

Adverse Events

Olanzapine

Serious events: 2 serious events
Other events: 42 other events
Deaths: 0 deaths

Risperidone

Serious events: 5 serious events
Other events: 43 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Olanzapine
n=68 participants at risk
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=62 participants at risk
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Immune system disorders
Asthma
0.00%
0/68
1.6%
1/62 • Number of events 1
Psychiatric disorders
Psychotic disorder
0.00%
0/68
1.6%
1/62 • Number of events 1
Psychiatric disorders
Schizoaffective disorder
1.5%
1/68 • Number of events 1
1.6%
1/62 • Number of events 2
Psychiatric disorders
Schizophrenia
1.5%
1/68 • Number of events 1
0.00%
0/62
Psychiatric disorders
Suicidal ideation
0.00%
0/68
1.6%
1/62 • Number of events 1
Vascular disorders
Hypotension
0.00%
0/68
1.6%
1/62 • Number of events 1

Other adverse events

Other adverse events
Measure
Olanzapine
n=68 participants at risk
Olanzapine, 5-20 mg, oral, capsules, daily, 12 weeks.
Risperidone
n=62 participants at risk
Risperidone, 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
Gastrointestinal disorders
Diarrhoea
5.9%
4/68 • Number of events 4
1.6%
1/62 • Number of events 1
Gastrointestinal disorders
Dry mouth
7.4%
5/68 • Number of events 5
8.1%
5/62 • Number of events 6
General disorders
Discomfort
7.4%
5/68 • Number of events 5
3.2%
2/62 • Number of events 2
Investigations
Weight increased
16.2%
11/68 • Number of events 11
6.5%
4/62 • Number of events 4
Metabolism and nutrition disorders
Increased appetite
7.4%
5/68 • Number of events 5
11.3%
7/62 • Number of events 7
Nervous system disorders
Headache
10.3%
7/68 • Number of events 9
12.9%
8/62 • Number of events 12
Nervous system disorders
Sedation
10.3%
7/68 • Number of events 8
6.5%
4/62 • Number of events 5
Psychiatric disorders
Anxiety
1.5%
1/68 • Number of events 1
9.7%
6/62 • Number of events 6
Psychiatric disorders
Insomnia
5.9%
4/68 • Number of events 5
11.3%
7/62 • Number of events 7

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60