Anew: Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03230864
• Collaborator: (none)
• Enrollment: 119
• Locations: 41
• Arms: 3
• Actual Duration (Months): 18.6
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS)

Condition or Disease	Intervention/Treatment	Phase
Treatment-resistant Schizophrenia	Drug: Lu AF35700; Drug: Risperidone; Drug: Olanzapine	Phase 3

Detailed Description

In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective confirmation (PC) period.

The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks), a Double-blind Treatment (DBT) Period (8 weeks), and a Safety Follow-up Period (6 weeks).

Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.

Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT period and were randomized into one of the 2 treatmetn arms (1:1) with either Lu AF35700 10 mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the dose set at the last visit of the PC period. This means that approximately half of the confirmed treatment-resistant patients were randomised back to the failed treatment in the PC period.

Data was not collected seperately for the DBT olanzapine and DBT risperidone participants, and there was no intent to compare Lu AF35700 to each drug seperately.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Interventional, Randomized, Double-blind, Active-controlled Study of the Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
• Actual Study Start Date: Jul 20, 2017
• Actual Primary Completion Date: Dec 23, 2018
• Actual Study Completion Date: Feb 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prospective Confirmation (PC) Period Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks	Drug: Risperidone; 4-6 mg/day, encapsulated tablets, orally; Drug: Olanzapine; 15-20 mg/day, encapsulated tablets, orally
Experimental: Double-blind treatment (DBT) period, Lu AF35700 10 mg Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks	Drug: Lu AF35700; 10 mg/day, encapsulated tablets, orally
Experimental: DBT Period, Continued treatment from PC Period Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period	Drug: Risperidone; 4-6 mg/day, encapsulated tablets, orally; Drug: Olanzapine; 15-20 mg/day, encapsulated tablets, orally

Outcome Measures

Primary Outcome Measures

1. Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score [From Randomization to Week 8]

   PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.

Secondary Outcome Measures

1. Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score [From Randomization to Week 8]

   CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening

2. Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score [From Randomization to Week 8]

   The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.

3. Change From Randomization to Week 8 in PANSS Marder Negative Factor Score [From Randomization to Week 8]

   The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.

4. Response [at Week 8]

   Response is defined as a ≥20% reduction in PANSS total score from Randomization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has schizophrenia, diagnosed according to DSM-5(TM). (Diagnostic and Statistical Manual of Mental Disorders) and confirmed by the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI-Schz).

• The patient is receiving treatment with a psychiatrist in either an inpatient or outpatient facility.

• The patient has been treated with adequate dose(s) of antipsychotic drug treatment for at least 2 weeks prior to the Screening Visit.

• The patient has failed to show an adequate response in the level of psychotic symptoms during at least one documented treatment trial with an adequate dose of an antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks) within 2 years prior to the Screening Visit. The failure to respond to the current antipsychotic drug treatment trial may be considered a retrospective failed treatment, if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic drug(s).

• The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥ "Moderate" on 1-7 scale) on at least 2 of the following PANSS items at the Screening and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the patient has a CGI-S score of ≥4 (≥ "Moderately ill") at the Screening and at Baseline 1 (Week 0) Visits.

Exclusion Criteria:

• The patient has any current primary psychiatric disorder other than schizophrenia, as assessed using the MINI-Schz.

• The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria).

• The patient is experiencing an acute exacerbation of his/her psychotic symptoms.

• The patient has been treated with, AND is resistant to, clozapine according to the investigator's judgement.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Health System	San Diego	California	United States	92103
2	Emory University Cognitive Neurology Clinic & ADRC	Atlanta	Georgia	United States	30329
3	Northwestern University	Chicago	Illinois	United States	60611
4	Corrigan Mental Health Center	Fall River	Massachusetts	United States	02720
5	University Of Massachusetts Medical Center	Worcester	Massachusetts	United States	01605-2610
6	Michigan Clinical Research Institute PC	Ann Arbor	Michigan	United States	48108
7	Kalamazoo Community Mental Health and Substance Abuse Services	Kalamazoo	Michigan	United States	49001
8	PsychCare Consultants Research	Saint Louis	Missouri	United States	63128
9	Creighton University	Omaha	Nebraska	United States	68131
10	Psychiatric and Behavioral Solutions	Salt Lake City	Utah	United States	84105
11	SPH - Kardzhali	Kardzhali		Bulgaria
12	State Psychiatric Hospital	Novi Iskar		Bulgaria
13	UMHAT	Pleven		Bulgaria
14	State Psychiatric Hospital	Radnevo		Bulgaria
15	DCC St. Vrach and St.St. Kuzma and Damian	Sofia		Bulgaria
16	MHC - Sofia	Sofia		Bulgaria
17	MHAT - Targovishte	Tărgovište		Bulgaria
18	Takeda General Hospital - JP0009	Aizu-Wakamatsu		Japan
19	Takeda General Hospital	Fukushima		Japan
20	Kohnodai Hospital	Ichikawa		Japan
21	Nara Medical University Hospital	Kashihara		Japan
22	University of Occupational and Environmental Health Hospital	Kitakyushu		Japan
23	Sankeikai Nishigahara Hospital - JP0008	Kita		Japan
24	National Center of Neurology and Psychiatry	Kodaira		Japan
25	Satokai Yuge Hospital	Kumamoto		Japan
26	NHO Ryukyu Hospital	Kunigami		Japan
27	Fujita Health University Hospital	Toyoake		Japan
28	Sverdlovsk Regional Clinical Psychiatric Hospital	Ekaterinburg		Russian Federation
29	GUZ Lipetsk Regional psychoneurological Hospital 1	Lipetsk		Russian Federation
30	Lipetsk Regional Psychoneurological Hospital	Lipetsk		Russian Federation
31	City Psychiatric Hospital # 6	Saint Petersburg		Russian Federation
32	Psychoneurological Dispensary #10	Saint Petersburg		Russian Federation
33	Psychoneurological Dispensary #1	Saint Petersburg		Russian Federation
34	Samara Psychiatric Hospital	Samara		Russian Federation
35	Tomsk National Research Medical Centre of the Russian Academy of Sciences	Tomsk		Russian Federation
36	Yaroslavl Regional Clinical Psychiatric Hospital	Yaroslavl		Russian Federation
37	Royal Edinburgh Hospital	Edinburgh		United Kingdom
38	The Maudsley Hospital - GB0001	London		United Kingdom
39	The Maudsley Hospital	London		United Kingdom
40	Manchester Mental Health & Social Care NHS Trust - GB0003	Manchester		United Kingdom
41	Manchester Mental Health & Social Care NHS Trust	Manchester		United Kingdom

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Study Director: Email contact via H.Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

• Study Protocol - Sep 7, 2018
• Statistical Analysis Plan - Mar 13, 2019

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT03230864
• Other Study ID Numbers: 17303A
• First Posted: Jul 27, 2017
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by H. Lundbeck A/S: Treatment-resistant schizophrenia; Lu AF35700
• Additional relevant MeSH terms: Schizophrenia; Olanzapine; Risperidone

Study Results

Participant Flow

Pre-assignment Detail	Patients who did not fulfil the randomization criteria for the DBT period, were withdrawn from the study after the PC period. Patients who fulfilled the randomization crietria for the DBT period, continued into the DBT period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm.

Arm/Group Title	Prospective Confirmation (PC) Period, Risperidone	PC Period, Olanzapine	Double-blind (DBT), Lu AF35700 10 mg	DBT, Continued Treatment From PC Period
Arm/Group Description	Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Risperidone: 4-6 mg/day, encapsulated tablets, orally	Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Olanzapine: 15-20 mg/day, encapsulated tablets, orally	Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	Patients in this arm will continue the treatment allocated in the PC period at the dose set at the last visit of the PC period. The analysis is made independent on which treatment the patient was done (risperidone or olanzapine). 8 weeks treatment.
Period Title: Prospective Confirmation (PC) Period
STARTED	68	51	0	0
COMPLETED	36	32	0	0
NOT COMPLETED	32	19	0	0
Period Title: Prospective Confirmation (PC) Period
STARTED	0	0	35	33
COMPLETED	0	0	27	31
NOT COMPLETED	0	0	8	2

Baseline Characteristics

Arm/Group Title	Non-randomized Patients	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg	DBT, Continued Treatment From PC Period	Total
Arm/Group Description	Patients not randomized to double-blind treatment period, i.e. withdrawn from the study during or after the PC period, were analyzed as one arm, independent of treatment	Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	Patients in this arm continued with the same treatment and dose as at the last visit of the PC period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm independent of treatment.	Total of all reporting groups
Overall Participants	51	35	33	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.6 (12.53)	42.9 (11.26)	42 (12.26)	42.5 (12)
Sex: Female, Male (Count of Participants)
Female	23 45.1%	15 42.9%	17 51.5%	55 46.2%
Male	28 54.9%	20 57.1%	16 48.5%	64 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2%	3 8.6%	2 6.1%	6 5%
Not Hispanic or Latino	50 98%	32 91.4%	30 90.9%	112 94.1%
Unknown or Not Reported	0 0%	0 0%	1 3%	1 0.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	5 9.8%	3 8.6%	3 9.1%	11 9.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	8 15.7%	0 0%	2 6.1%	10 8.4%
White	38 74.5%	31 88.6%	27 81.8%	96 80.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 2.9%	1 3%	2 1.7%
PANSS total score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	98.1 (10.78)	102.3 (12)	101.6 (11.95)	100.3 (11.54)
CGI-S score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.8 (0.64)	4.8 (0.57)	4.9 (0.55)	4.82 (0.59)

Outcome Measures

1. Primary Outcome

Title	Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
Description	PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the full-analysis set (FAS) with a week 8 observation

Arm/Group Title	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg	DBT, Continued Treatment From PC Period
Arm/Group Description	Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Measure Participants	27	31
Mean (Standard Error) [units on a scale]	-4.71 (2.22)	-10.19 (2.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg, DBT, Continued Treatment From PC Period
	Comments	The mean changes from randomization in PANNS total score was analysed using a mixed model for repeated measures (MMRM) approach. The model will include the fixed, categorical effects of treatment, strata, visit, treatment-by-visit interaction, fixed covariates of baseline scores and baseline scores-by-visit interaction. An unstructured (co)variance structure will be used to model the within-patient errors. The Kenward-Roger approximation will be used to estimate denominator degrees of freedom.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0809
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.47
	Confidence Interval	(2-Sided) 95%; -0.70 to 11.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
Description	CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation

Arm/Group Title	DBT, Lu AF35700 10 mg	DBT, Continued Treatment
Arm/Group Description	10 mg encapsulated tablets administered orally, once daily. Lu AF35700: 10 mg/day, encapsulated tablets, orally	Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Measure Participants	27	31
Mean (Standard Error) [units on a scale]	-0.18 (0.12)	-0.37 (0.11)

3. Secondary Outcome

Title	Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
Description	The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation

Arm/Group Title	DBT, Lu AF35700 10 mg	DBT, Continued Treatment
Arm/Group Description	10 mg encapsulated tablets administered orally, once daily. Lu AF35700: 10 mg/day, encapsulated tablets, orally	Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Measure Participants	27	31
Mean (Standard Error) [units on a scale]	-2.99 (1.64)	-3.14 (1.58)

4. Secondary Outcome

Title	Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
Description	The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation

Arm/Group Title	DBT, Lu AF35700 10 mg	DBT, Continued Treatment
Arm/Group Description	10 mg encapsulated tablets administered orally, once daily. Lu AF35700: 10 mg/day, encapsulated tablets, orally	Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Measure Participants	27	31
Mean (Standard Error) [units on a scale]	-1.51 (0.77)	-1.74 (0.75)

5. Secondary Outcome

Title	Response
Description	Response is defined as a ≥20% reduction in PANSS total score from Randomization
Time Frame	at Week 8

Outcome Measure Data

Analysis Population Description

Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation

Arm/Group Title	DBT, Lu AF35700 10 mg	DBT, Continued Treatment
Arm/Group Description	10 mg encapsulated tablets administered orally, once daily. Lu AF35700: 10 mg/day, encapsulated tablets, orally	Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Measure Participants	27	31
Count of Participants [Participants]	6 11.8%	13 37.1%

Adverse Events

Time Frame	20 weeks
Arm/Group Title	Prospective Confirmation (PC) Period - Risperidone		PC Period - Olanzapine		Double Blind Treatment (DBT) Period - Lu AF35700 10 mg		DBT Period, Continued Treatment From PC Period
Arm/Group Description	Patients not randomized to double-blind treatment		Patients not randomized to double-blind treatment		Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks		Patients in this arm continued with the same treatment and dose as at the last visit of the PC Period. This arm is analyzed as one single treatment arm independent on which treatment was administered (olanzapine or risperidone for 8 weeks).
All Cause Mortality
	Prospective Confirmation (PC) Period - Risperidone		PC Period - Olanzapine		Double Blind Treatment (DBT) Period - Lu AF35700 10 mg		DBT Period, Continued Treatment From PC Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/51 (0%)		0/35 (0%)		0/33 (0%)
Serious Adverse Events
	Prospective Confirmation (PC) Period - Risperidone		PC Period - Olanzapine		Double Blind Treatment (DBT) Period - Lu AF35700 10 mg		DBT Period, Continued Treatment From PC Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/68 (1.5%)		1/51 (2%)		0/35 (0%)		0/33 (0%)
Psychiatric disorders
Suicidal ideation	1/68 (1.5%)	1	0/51 (0%)	0	0/35 (0%)	0	0/33 (0%)	0
Vascular disorders
Hypertension	0/68 (0%)	0	1/51 (2%)	1	0/35 (0%)	0	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	Prospective Confirmation (PC) Period - Risperidone		PC Period - Olanzapine		Double Blind Treatment (DBT) Period - Lu AF35700 10 mg		DBT Period, Continued Treatment From PC Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/68 (23.5%)		3/51 (5.9%)		8/35 (22.9%)		7/33 (21.2%)
Investigations
Weight increased	1/68 (1.5%)	1	0/51 (0%)	0	1/35 (2.9%)	1	3/33 (9.1%)	3
Nervous system disorders
Akathisia	4/68 (5.9%)	4	0/51 (0%)	0	0/35 (0%)	0	0/33 (0%)	0
Psychiatric disorders
Anxiety	6/68 (8.8%)	7	1/51 (2%)	1	4/35 (11.4%)	4	1/33 (3%)	1
Insomnia	4/68 (5.9%)	4	0/51 (0%)	0	1/35 (2.9%)	1	2/33 (6.1%)	2
Schizophrenia	1/68 (1.5%)	1	2/51 (3.9%)	2	2/35 (5.7%)	2	1/33 (3%)	1

Limitations/Caveats

The study was terminated early and hence the statistical analysis was conducted on a smaller sample size than originally planned.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.