Trial Outcomes & Findings for Study in Adolescents With Schizophrenia or Bipolar Disorder (NCT NCT00982020)

NCT ID: NCT00982020

Last Updated: 2014-12-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 203 participants
• Primary outcome timeframe: Baseline, 52 weeks
• Results posted on: 2014-12-17

Participant Flow

Participant milestones

Measure	Olanzapine/Standard Behavioral Weight Intervention Olanzapine: 2.5 milligrams (mg) to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Overall Study STARTED	102	101
Overall Study Received at Least 1 Dose of Study Drug	102	101
Overall Study COMPLETED	45	37
Overall Study NOT COMPLETED	57	64

Reasons for withdrawal

Measure	Olanzapine/Standard Behavioral Weight Intervention Olanzapine: 2.5 milligrams (mg) to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Overall Study Adverse Event	19	15
Overall Study Withdrawal by Subject	11	14
Overall Study Lost to Follow-up	5	11
Overall Study Lack of Efficacy	10	4
Overall Study Parent/Caregiver Decision	5	5
Overall Study Treatment Non-compliance	3	6
Overall Study Physician Decision	2	5
Overall Study Entry Criteria Not Met	2	1
Overall Study Protocol Violation	0	2
Overall Study Clinical Relapse	0	1

Baseline Characteristics

Study in Adolescents With Schizophrenia or Bipolar Disorder

Baseline characteristics by cohort

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits	Total n=203 Participants Total of all reporting groups
Age, Continuous	15.86 years STANDARD_DEVIATION 1.49 • n=5 Participants	15.66 years STANDARD_DEVIATION 1.52 • n=7 Participants	15.76 years STANDARD_DEVIATION 1.51 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	47 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	54 Participants n=7 Participants	106 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	87 Participants n=5 Participants	92 Participants n=7 Participants	179 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	84 Participants n=5 Participants	80 Participants n=7 Participants	164 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Germany	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Poland	6 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Russian Federation	28 participants n=5 Participants	27 participants n=7 Participants	55 participants n=5 Participants
Region of Enrollment United States	53 participants n=5 Participants	54 participants n=7 Participants	107 participants n=5 Participants
Region of Enrollment Puerto Rico	13 participants n=5 Participants	7 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants who received at least one dose of study drug. Mixed model repeated measures (MMRM) methodology used.

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to 52 Weeks in Body Mass Index (BMI) for All Participants	3.64 kilograms per meter squared (kg/m^2) Standard Error .39	2.83 kilograms per meter squared (kg/m^2) Standard Error .40

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants who received at least one dose of study drug and who had at least 6 months of data. Last observation carried forward (LOCF) methodology.

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=54 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=55 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to Endpoint in Body Mass Index (BMI) for Participants With Duration of Treatment of at Least 6 Months	3.36 kg/m^2 Standard Error 0.41	2.99 kg/m^2 Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline up to 52 weeks

Population: 65 participants (32%; 34% in Standard Group \[SG\], 30% in Intense Group \[IG\]) did not meet 7% weight gain criterion \[WGC\] by the time they discontinued. 122 participants (60%; 58% in SG, 62% in IG) did not meet 15% WGC by the time they discontinued. 161 participants (79%; 76% in SG, 82% in IG) did not meet 25% WGC by the time they discontinued.

Kaplan-Meier methodology used to estimate time to event. Participants who never reached the target weight gain contributed to the set of patients at risk up to the point at which they discontinued from the study and were then censored (i.e., removed from the risk set).

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Time to Event for 7%, 15%, and 25% Weight Gain for All Participants Time to First 7% Weight Gain	57 days Interval 44.0 to 84.0	57 days Interval 44.0 to 84.0
Time to Event for 7%, 15%, and 25% Weight Gain for All Participants Time to First 15% Weight Gain	197 days Interval 140.0 to 359.0	198 days Interval 141.0 to There was an insufficient number of events of 15% weight gain in the Intense group to compute this statistic.
Time to Event for 7%, 15%, and 25% Weight Gain for All Participants Time to First 25% Weight Gain	NA days There was an insufficient number of events of 25% weight gain in the Standard group to compute these statistics.	NA days There was an insufficient number of events of 25% weight gain in the Intense group to compute these statistics.

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with bipolar I disorder, who received at least one dose of study drug. Mixed model repeated measures (MMRM) methodology.

The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 (symptom not present) to 60 (symptom extremely severe).

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=58 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=58 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to 52 Weeks in Adolescent Structured Young Mania Rating Scale (YMRS) for Participants With Bipolar I Disorder	-17.66 units on a scale Standard Error 1.75	-12.05 units on a scale Standard Error 1.92

SECONDARY outcome

Timeframe: 52 weeks

Population: All randomized participants who received at least one dose of study drug. Mixed model repeated measures (MMRM) methodology.

The Clinical Global Impression of Improvement (CGI-I) is used by the clinician to record the improvement of illness at the time of assessment. The score ranges from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Clinical Global Impression of Improvement (CGI-I) at 52 Weeks for All Participants	2.04 units on a scale Standard Error 0.15	2.29 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants who received at least one dose of study drug.

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to 52 Weeks in Waist Circumference for All Participants	7.22 centimeters (cm) Standard Error 1.06	7.31 centimeters (cm) Standard Error 1.11

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants who received at least one dose of study drug. Mixed model repeated measures (MMRM) methodology.

The CGI-S is used by the clinician to record the severity of illness at the time of assessment. The score ranges from 1 = normal, not at all ill to 7 = among the most extremely ill.

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to 52 Weeks in Clinical Global Impression - Severity (CGI-S) for All Participants	-2.06 units on a scale Standard Error 0.14	-1.74 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with schizophrenia who received at least one dose of study drug. Mixed model repeated measures (MMRM) methodology.

The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.

Outcome measures

Measure	Olanzapine/Standard Behavioral Weight Intervention n=44 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=43 Participants Olanzapine: 2.5 mg to 20 mg given orally, daily for 52 weeks. Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits
Mean Change From Baseline to 52 Weeks in Anchored Version of the Brief Psychiatric Rating Scale for Children (BPRS-C) for Participants With Schizophrenia	-28.00 units on a scale Standard Error 2.83	-30.96 units on a scale Standard Error 2.67

Adverse Events

Olanzapine/Standard Behavioral Weight Intervention

Serious events: 13 serious events

Other events: 81 other events

Deaths: 0 deaths

Olanzapine/Intense Behavioral Weight Intervention

Serious events: 20 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 participants at risk Olanzapine: 2.5mg to 20mg given orally, daily for 52 weeks Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 participants at risk Olanzapine: 2.5mg to 20mg given orally, daily for 52 weeks Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits.
Gastrointestinal disorders Gastroduodenitis	0.00% 0/102	0.99% 1/101 • Number of events 1
General disorders Irritability	0.00% 0/102	0.99% 1/101 • Number of events 2
Infections and infestations Gastroenteritis viral	0.98% 1/102 • Number of events 1	0.00% 0/101
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Fall	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Hip fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Humerus fracture	0.98% 1/102 • Number of events 1	0.00% 0/101
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Overdose	0.98% 1/102 • Number of events 1	0.00% 0/101
Injury, poisoning and procedural complications Rib fracture	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Traumatic liver injury	0.00% 0/102	0.99% 1/101 • Number of events 1
Injury, poisoning and procedural complications Traumatic lung injury	0.00% 0/102	0.99% 1/101 • Number of events 1
Nervous system disorders Neuroleptic malignant syndrome	0.98% 1/102 • Number of events 1	0.00% 0/101
Psychiatric disorders Abnormal behaviour	0.00% 0/102	0.99% 1/101 • Number of events 2
Psychiatric disorders Aggression	0.00% 0/102	0.99% 1/101 • Number of events 1
Psychiatric disorders Bipolar disorder	0.00% 0/102	2.0% 2/101 • Number of events 2
Psychiatric disorders Bipolar i disorder	0.00% 0/102	4.0% 4/101 • Number of events 4
Psychiatric disorders Drug abuse	0.98% 1/102 • Number of events 1	0.00% 0/101
Psychiatric disorders Hallucination, auditory	0.00% 0/102	0.99% 1/101 • Number of events 1
Psychiatric disorders Mental disorder	0.00% 0/102	0.99% 1/101 • Number of events 1
Psychiatric disorders Psychotic disorder	0.98% 1/102 • Number of events 1	4.0% 4/101 • Number of events 5
Psychiatric disorders Schizophrenia	0.98% 1/102 • Number of events 1	0.00% 0/101
Psychiatric disorders Schizophrenia, paranoid type	0.98% 1/102 • Number of events 1	0.00% 0/101
Psychiatric disorders Suicidal ideation	2.9% 3/102 • Number of events 3	2.0% 2/101 • Number of events 2
Psychiatric disorders Suicide attempt	2.0% 2/102 • Number of events 2	0.00% 0/101
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.98% 1/102 • Number of events 1	0.00% 0/101

Other adverse events

Measure	Olanzapine/Standard Behavioral Weight Intervention n=102 participants at risk Olanzapine: 2.5mg to 20mg given orally, daily for 52 weeks Standard behavioral weight intervention: One time counseling and basic counseling information on healthy eating and exercise habits at randomization visit only	Olanzapine/Intense Behavioral Weight Intervention n=101 participants at risk Olanzapine: 2.5mg to 20mg given orally, daily for 52 weeks Intense behavioral weight intervention: Counseling provided at randomization and at all subsequent study visits by appropriately trained individual regarding healthy lifestyle habits. Participants also provided with simple tools to help enable healthy eating and exercise habits.
Gastrointestinal disorders Dry mouth	5.9% 6/102 • Number of events 6	4.0% 4/101 • Number of events 4
Gastrointestinal disorders Vomiting	6.9% 7/102 • Number of events 8	4.0% 4/101 • Number of events 7
General disorders Fatigue	8.8% 9/102 • Number of events 10	5.9% 6/101 • Number of events 6
Infections and infestations Nasopharyngitis	13.7% 14/102 • Number of events 16	10.9% 11/101 • Number of events 11
Investigations Blood creatine phosphokinase increased	6.9% 7/102 • Number of events 9	5.0% 5/101 • Number of events 6
Investigations Blood insulin increased	9.8% 10/102 • Number of events 11	6.9% 7/101 • Number of events 7
Investigations Weight increased	30.4% 31/102 • Number of events 31	20.8% 21/101 • Number of events 21
Metabolism and nutrition disorders Increased appetite	15.7% 16/102 • Number of events 16	12.9% 13/101 • Number of events 14
Nervous system disorders Dizziness	6.9% 7/102 • Number of events 7	2.0% 2/101 • Number of events 2
Nervous system disorders Headache	18.6% 19/102 • Number of events 49	19.8% 20/101 • Number of events 30
Nervous system disorders Sedation	7.8% 8/102 • Number of events 8	3.0% 3/101 • Number of events 5
Nervous system disorders Somnolence	18.6% 19/102 • Number of events 22	23.8% 24/101 • Number of events 28
Psychiatric disorders Anxiety	5.9% 6/102 • Number of events 6	3.0% 3/101 • Number of events 4
Reproductive system and breast disorders Dysmenorrhoea	6.0% 3/50 • Number of events 18	2.1% 1/47 • Number of events 4
Respiratory, thoracic and mediastinal disorders Cough	6.9% 7/102 • Number of events 8	3.0% 3/101 • Number of events 5

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