Trial Outcomes & Findings for Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine (NCT NCT00401973)
NCT ID: NCT00401973
Last Updated: 2009-10-06
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
199 participants
Primary outcome timeframe
Baseline to endpoint (22 weeks)
Results posted on
2009-10-06
Participant Flow
Participant milestones
| Measure |
Olanzapine
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
76
|
73
|
|
Overall Study
COMPLETED
|
39
|
50
|
50
|
|
Overall Study
NOT COMPLETED
|
11
|
26
|
23
|
Reasons for withdrawal
| Measure |
Olanzapine
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
8
|
4
|
|
Overall Study
Clinical Relapse
|
0
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
2
|
|
Overall Study
Physician Decision
|
2
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
2
|
3
|
|
Overall Study
Sponsor Decision
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
12
|
9
|
Baseline Characteristics
Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine
Baseline characteristics by cohort
| Measure |
Olanzapine
n=50 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=76 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=73 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Total
n=199 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
38.7 years
STANDARD_DEVIATION 12.89 • n=93 Participants
|
38.2 years
STANDARD_DEVIATION 11.40 • n=4 Participants
|
38.7 years
STANDARD_DEVIATION 12.01 • n=27 Participants
|
38.5 years
STANDARD_DEVIATION 11.95 • n=483 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
79 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
120 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=93 Participants
|
22 participants
n=4 Participants
|
21 participants
n=27 Participants
|
56 participants
n=483 Participants
|
|
Region of Enrollment
Mexico
|
7 participants
n=93 Participants
|
9 participants
n=4 Participants
|
11 participants
n=27 Participants
|
27 participants
n=483 Participants
|
|
Region of Enrollment
Puerto Rico
|
5 participants
n=93 Participants
|
8 participants
n=4 Participants
|
5 participants
n=27 Participants
|
18 participants
n=483 Participants
|
|
Region of Enrollment
Israel
|
5 participants
n=93 Participants
|
8 participants
n=4 Participants
|
9 participants
n=27 Participants
|
22 participants
n=483 Participants
|
|
Region of Enrollment
Russian Federation
|
11 participants
n=93 Participants
|
15 participants
n=4 Participants
|
14 participants
n=27 Participants
|
40 participants
n=483 Participants
|
|
Region of Enrollment
Korea, Republic of
|
9 participants
n=93 Participants
|
14 participants
n=4 Participants
|
13 participants
n=27 Participants
|
36 participants
n=483 Participants
|
|
Race/Ethnicity
African
|
2 participants
n=93 Participants
|
10 participants
n=4 Participants
|
4 participants
n=27 Participants
|
16 participants
n=483 Participants
|
|
Race/Ethnicity
Caucasian
|
23 participants
n=93 Participants
|
30 participants
n=4 Participants
|
34 participants
n=27 Participants
|
87 participants
n=483 Participants
|
|
Race/Ethnicity
East Asian
|
10 participants
n=93 Participants
|
15 participants
n=4 Participants
|
14 participants
n=27 Participants
|
39 participants
n=483 Participants
|
|
Race/Ethnicity
Hispanic
|
14 participants
n=93 Participants
|
20 participants
n=4 Participants
|
18 participants
n=27 Participants
|
52 participants
n=483 Participants
|
|
Race/Ethnicity
Native American
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
1 participants
n=483 Participants
|
|
Race/Ethnicity
West Asian
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
4 participants
n=483 Participants
|
|
Type of Diagnosis
Schizoaffective
|
8 participants
n=93 Participants
|
15 participants
n=4 Participants
|
18 participants
n=27 Participants
|
41 participants
n=483 Participants
|
|
Type of Diagnosis
Schizophrenia
|
42 participants
n=93 Participants
|
61 participants
n=4 Participants
|
55 participants
n=27 Participants
|
158 participants
n=483 Participants
|
|
Body Mass Index (BMI)
|
27.0 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 4.53 • n=93 Participants
|
27.3 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 4.67 • n=4 Participants
|
27.0 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 4.84 • n=27 Participants
|
27.1 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 4.68 • n=483 Participants
|
|
Onset Age
|
24.35 years
STANDARD_DEVIATION 8.42 • n=93 Participants
|
26.44 years
STANDARD_DEVIATION 9.98 • n=4 Participants
|
24.40 years
STANDARD_DEVIATION 9.18 • n=27 Participants
|
25.15 years
STANDARD_DEVIATION 9.32 • n=483 Participants
|
|
Previous Number of Episodes
|
1.53 number of episodes
STANDARD_DEVIATION 1.02 • n=93 Participants
|
2.19 number of episodes
STANDARD_DEVIATION 5.90 • n=4 Participants
|
2.22 number of episodes
STANDARD_DEVIATION 5.77 • n=27 Participants
|
2.04 number of episodes
STANDARD_DEVIATION 5.06 • n=483 Participants
|
|
Weight
|
77.0 kilograms
STANDARD_DEVIATION 16.33 • n=93 Participants
|
79.1 kilograms
STANDARD_DEVIATION 17.27 • n=4 Participants
|
76.2 kilograms
STANDARD_DEVIATION 16.22 • n=27 Participants
|
77.5 kilograms
STANDARD_DEVIATION 16.62 • n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement.
Outcome measures
| Measure |
Olanzapine
n=40 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=50 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=51 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Change From Baseline to Endpoint in Weight
|
2.76 kilograms
Standard Error 0.75
|
2.40 kilograms
Standard Error 0.65
|
0.65 kilograms
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=42 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=49 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=56 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Fasting Triglycerides
Baseline
|
1.58 millimoles per Liter (mmol/L)
Standard Deviation 0.81
|
1.61 millimoles per Liter (mmol/L)
Standard Deviation 0.76
|
1.68 millimoles per Liter (mmol/L)
Standard Deviation 1.00
|
|
Mean Change From Baseline to Endpoint in Fasting Triglycerides
Change from Baseline
|
0.33 millimoles per Liter (mmol/L)
Standard Deviation 1.01
|
0.35 millimoles per Liter (mmol/L)
Standard Deviation 0.88
|
0.06 millimoles per Liter (mmol/L)
Standard Deviation 0.64
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=42 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=49 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=56 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
Baseline
|
5.01 millimole per Liter (mmol/L)
Standard Deviation 1.00
|
5.03 millimole per Liter (mmol/L)
Standard Deviation 1.09
|
4.91 millimole per Liter (mmol/L)
Standard Deviation 1.21
|
|
Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
Change from Baseline
|
0.36 millimole per Liter (mmol/L)
Standard Deviation 0.84
|
0.01 millimole per Liter (mmol/L)
Standard Deviation 1.06
|
-0.08 millimole per Liter (mmol/L)
Standard Deviation 0.92
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: Number of randomized participants with a baseline and at least one post-baseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=46 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=63 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=64 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
Baseline
|
1.25 millimole per liter (mmol/L)
Standard Deviation 0.29
|
1.26 millimole per liter (mmol/L)
Standard Deviation 0.36
|
1.22 millimole per liter (mmol/L)
Standard Deviation 0.35
|
|
Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
Change from Baseline
|
-0.00 millimole per liter (mmol/L)
Standard Deviation 0.23
|
-0.11 millimole per liter (mmol/L)
Standard Deviation 0.25
|
-0.08 millimole per liter (mmol/L)
Standard Deviation 0.24
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=40 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=47 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=55 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
Baseline
|
3.02 millimole per Liter (mmol/L)
Standard Deviation 0.88
|
3.06 millimole per Liter (mmol/L)
Standard Deviation 1.03
|
2.91 millimole per Liter (mmol/L)
Standard Deviation 0.93
|
|
Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
Change from Baseline
|
0.16 millimole per Liter (mmol/L)
Standard Deviation 0.60
|
-0.04 millimole per Liter (mmol/L)
Standard Deviation 0.95
|
-0.02 millimole per Liter (mmol/L)
Standard Deviation 0.84
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=44 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=59 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=64 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Fasting Glucose
Baseline
|
5.32 millimole per Liter (mmol/L)
Standard Deviation 0.46
|
5.25 millimole per Liter (mmol/L)
Standard Deviation 0.78
|
5.28 millimole per Liter (mmol/L)
Standard Deviation 0.63
|
|
Mean Change From Baseline to Endpoint in Fasting Glucose
Change from Baseline
|
0.26 millimole per Liter (mmol/L)
Standard Deviation 0.99
|
0.10 millimole per Liter (mmol/L)
Standard Deviation 0.48
|
0.01 millimole per Liter (mmol/L)
Standard Deviation 0.58
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: All randomized participants with baseline and at least one postbaseline measurement. Last post-baseline measurement carried forward.
Outcome measures
| Measure |
Olanzapine
n=44 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=63 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=63 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Mean Change From Baseline to Endpoint in Hemoglobin A1c
Baseline
|
5.51 percent hemoglobin A1c
Standard Deviation 0.46
|
5.48 percent hemoglobin A1c
Standard Deviation 0.39
|
5.53 percent hemoglobin A1c
Standard Deviation 0.37
|
|
Mean Change From Baseline to Endpoint in Hemoglobin A1c
Change from Baseline
|
0.09 percent hemoglobin A1c
Standard Deviation 0.45
|
0.10 percent hemoglobin A1c
Standard Deviation 0.37
|
-0.03 percent hemoglobin A1c
Standard Deviation 0.25
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
The BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Each item is rated on a scale from 1 (symptom not present) to 7 (symptom extremely severe). The BPRS total score ranges from 18 to 126.
Outcome measures
| Measure |
Olanzapine
n=45 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=67 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=72 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score
Baseline
|
48.24 units on a scale
Standard Deviation 15.98
|
45.90 units on a scale
Standard Deviation 12.44
|
47.00 units on a scale
Standard Deviation 14.18
|
|
Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score
Change from Baseline
|
-13.89 units on a scale
Standard Deviation 18.61
|
-9.90 units on a scale
Standard Deviation 11.24
|
-9.72 units on a scale
Standard Deviation 14.15
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
The MADRS is a rating scale for severity of depressive mood 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).
Outcome measures
| Measure |
Olanzapine
n=46 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=67 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=72 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Baseline
|
12.76 units on a scale
Standard Deviation 8.08
|
14.22 units on a scale
Standard Deviation 11.14
|
15.40 units on a scale
Standard Deviation 9.21
|
|
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Change from Baseline
|
-6.39 units on a scale
Standard Deviation 8.37
|
-4.12 units on a scale
Standard Deviation 7.20
|
-4.36 units on a scale
Standard Deviation 7.47
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: Number of participants with a baseline and at least one post baseline measurement. Last post-baseline measurement carried forward.
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Outcome measures
| Measure |
Olanzapine
n=47 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=72 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
n=73 Participants
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S)
Baseline
|
4.06 units on a scale
Standard Deviation 1.24
|
4.03 units on a scale
Standard Deviation 1.07
|
4.00 units on a scale
Standard Deviation 1.13
|
|
Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S)
Change from Baseline
|
-0.98 units on a scale
Standard Deviation 1.13
|
-0.72 units on a scale
Standard Deviation 1.14
|
-0.79 units on a scale
Standard Deviation 1.03
|
SECONDARY outcome
Timeframe: Baseline to endpoint (22 weeks)Population: N=Pairs of Observations for the combined treatment groups.
To understand the drivers of weight gain as indicated by the correlation between weight changes and changes in the Eating Inventory (EI) and Food Craving Inventory (FCI). The EI is a 51-item inventory that measures dietary restraint, disinhibition, and perceived hunger. The FCI is a 28-item instrument measuring the frequency over the past month of general cravings and cravings for specific types of foods, namely: high fats, sweets, carbohydrates/starches, and fast-food fats. Correlations were computed on the combined treatment groups.
Outcome measures
| Measure |
Olanzapine
n=66 Participants
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
n=41 Participants
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
FCI: Total Score (N=184, N=137)
|
0.039 correlation
|
-0.000 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
EI: Disinhibition
|
-0.034 correlation
|
0.285 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
EI: Cognitive Restraint
|
-0.273 correlation
|
-0.038 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
EI: Hunger
|
-0.150 correlation
|
0.148 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
FCI: Carbohydrates/Starches (N=186, N=141)
|
0.013 correlation
|
-0.064 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
FCI: Fast Food Fats (N=188, N=140)
|
-0.019 correlation
|
0.047 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
FCI: High Fats (N=186, N=138)
|
0.051 correlation
|
0.043 correlation
|
—
|
|
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
FCI: Sweets (N=187, N=140)
|
0.022 correlation
|
-0.008 correlation
|
—
|
Adverse Events
Olanzapine
Serious events: 5 serious events
Other events: 26 other events
Deaths: 0 deaths
Olanzapine + Amantadine
Serious events: 4 serious events
Other events: 38 other events
Deaths: 0 deaths
Olanzapine + Metformin
Serious events: 4 serious events
Other events: 46 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Olanzapine
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
General disorders
Chest pain
|
0.00%
0/50
|
0.00%
0/76
|
1.4%
1/73 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/50
|
1.3%
1/76 • Number of events 1
|
0.00%
0/73
|
|
Nervous system disorders
Akathisia
|
0.00%
0/50
|
1.3%
1/76 • Number of events 1
|
0.00%
0/73
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/50
|
1.3%
1/76 • Number of events 1
|
2.7%
2/73 • Number of events 2
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/50
|
1.3%
1/76 • Number of events 1
|
0.00%
0/73
|
|
Psychiatric disorders
Psychotic disorder
|
2.0%
1/50 • Number of events 1
|
0.00%
0/76
|
0.00%
0/73
|
|
Psychiatric disorders
Schizophrenia
|
6.0%
3/50 • Number of events 3
|
0.00%
0/76
|
0.00%
0/73
|
|
Psychiatric disorders
Suicidal ideation
|
2.0%
1/50 • Number of events 1
|
0.00%
0/76
|
0.00%
0/73
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/50
|
0.00%
0/76
|
1.4%
1/73 • Number of events 1
|
Other adverse events
| Measure |
Olanzapine
olanzapine plus behavioral information. olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks.
|
Olanzapine + Amantadine
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. amantadine: 100 mg, oral, twice a day. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
Olanzapine + Metformin
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information.
olanzapine: 5-20 milligrams (mg), oral, daily for 22 weeks. metformin: 500 mg, oral, twice a day for 2 weeks, titrated to 500 mg three times a day thereafter. zonisamide: 100-400 mg, oral, daily (only if patient gained greater than 3 kilograms).
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/50
|
3.9%
3/76 • Number of events 3
|
4.1%
3/73 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/50
|
3.9%
3/76 • Number of events 3
|
13.7%
10/73 • Number of events 11
|
|
Gastrointestinal disorders
Dry mouth
|
4.0%
2/50 • Number of events 2
|
5.3%
4/76 • Number of events 4
|
0.00%
0/73
|
|
Gastrointestinal disorders
Nausea
|
4.0%
2/50 • Number of events 2
|
3.9%
3/76 • Number of events 3
|
6.8%
5/73 • Number of events 6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/50
|
1.3%
1/76 • Number of events 1
|
6.8%
5/73 • Number of events 5
|
|
General disorders
Asthenia
|
2.0%
1/50 • Number of events 1
|
0.00%
0/76
|
4.1%
3/73 • Number of events 3
|
|
General disorders
Fatigue
|
2.0%
1/50 • Number of events 1
|
2.6%
2/76 • Number of events 2
|
4.1%
3/73 • Number of events 3
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/50
|
5.3%
4/76 • Number of events 4
|
0.00%
0/73
|
|
Infections and infestations
Urinary tract infection
|
4.0%
2/50 • Number of events 2
|
0.00%
0/76
|
0.00%
0/73
|
|
Injury, poisoning and procedural complications
Overdose
|
4.0%
2/50 • Number of events 2
|
0.00%
0/76
|
0.00%
0/73
|
|
Investigations
Weight increased
|
4.0%
2/50 • Number of events 3
|
5.3%
4/76 • Number of events 4
|
5.5%
4/73 • Number of events 4
|
|
Metabolism and nutrition disorders
Increased appetite
|
6.0%
3/50 • Number of events 4
|
1.3%
1/76 • Number of events 1
|
4.1%
3/73 • Number of events 3
|
|
Nervous system disorders
Akathisia
|
4.0%
2/50 • Number of events 2
|
3.9%
3/76 • Number of events 3
|
2.7%
2/73 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
4.0%
2/50 • Number of events 2
|
1.3%
1/76 • Number of events 1
|
2.7%
2/73 • Number of events 2
|
|
Nervous system disorders
Headache
|
4.0%
2/50 • Number of events 2
|
2.6%
2/76 • Number of events 2
|
5.5%
4/73 • Number of events 4
|
|
Nervous system disorders
Sedation
|
0.00%
0/50
|
5.3%
4/76 • Number of events 4
|
2.7%
2/73 • Number of events 2
|
|
Nervous system disorders
Somnolence
|
8.0%
4/50 • Number of events 4
|
6.6%
5/76 • Number of events 5
|
11.0%
8/73 • Number of events 10
|
|
Psychiatric disorders
Anxiety
|
4.0%
2/50 • Number of events 2
|
3.9%
3/76 • Number of events 3
|
2.7%
2/73 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
10.0%
5/50 • Number of events 5
|
5.3%
4/76 • Number of events 5
|
1.4%
1/73 • Number of events 3
|
|
Psychiatric disorders
Sleep disorder
|
4.0%
2/50 • Number of events 2
|
0.00%
0/76
|
1.4%
1/73 • Number of events 1
|
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