Trial Outcomes & Findings for Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia (NCT NCT03230864)

Last Updated: 2020-01-21

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

119 participants

Primary outcome timeframe

From Randomization to Week 8

Results posted on

2020-01-21

Participant Flow

Patients who did not fulfil the randomization criteria for the DBT period, were withdrawn from the study after the PC period.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

Participant milestones

Participant milestones
Measure	Prospective Confirmation (PC) Period, Risperidone Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Risperidone: 4-6 mg/day, encapsulated tablets, orally	PC Period, Olanzapine Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Olanzapine: 15-20 mg/day, encapsulated tablets, orally	Double-blind (DBT), Lu AF35700 10 mg Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period 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.
Prospective Confirmation (PC) Period STARTED	68	51	0	0
Prospective Confirmation (PC) Period COMPLETED	36	32	0	0
Prospective Confirmation (PC) Period NOT COMPLETED	32	19	0	0
Double Blind Treatment (DBT) Period STARTED	0	0	35	33
Double Blind Treatment (DBT) Period COMPLETED	0	0	27	31
Double Blind Treatment (DBT) Period NOT COMPLETED	0	0	8	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Prospective Confirmation (PC) Period, Risperidone Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Risperidone: 4-6 mg/day, encapsulated tablets, orally	PC Period, Olanzapine Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Olanzapine: 15-20 mg/day, encapsulated tablets, orally	Double-blind (DBT), Lu AF35700 10 mg Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period 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.
Prospective Confirmation (PC) Period Adverse Event	3	0	0	0
Prospective Confirmation (PC) Period Lack of Efficacy	0	2	0	0
Prospective Confirmation (PC) Period Protocol Violation	1	2	0	0
Prospective Confirmation (PC) Period Withdrawal by Subject	4	1	0	0
Prospective Confirmation (PC) Period Did not fulfill rand criteria DBT	14	5	0	0
Prospective Confirmation (PC) Period Sponsor Decision	9	9	0	0
Prospective Confirmation (PC) Period Study Personnel Decision	1	0	0	0
Double Blind Treatment (DBT) Period Adverse Event	0	0	5	1
Double Blind Treatment (DBT) Period Withdrawal by Subject	0	0	1	1
Double Blind Treatment (DBT) Period Sponsor Decision	0	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=35 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=33 Participants 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 n=119 Participants Total of all reporting groups	Non-randomized Patients n=51 Participants 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
Age, Continuous	42.9 years STANDARD_DEVIATION 11.26 • n=7 Participants	42 years STANDARD_DEVIATION 12.26 • n=5 Participants	42.5 years STANDARD_DEVIATION 12 • n=4 Participants	42.6 years STANDARD_DEVIATION 12.53 • n=5 Participants
Sex: Female, Male Female	15 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=7 Participants	16 Participants n=5 Participants	64 Participants n=4 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=7 Participants	30 Participants n=5 Participants	112 Participants n=4 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=7 Participants	27 Participants n=5 Participants	96 Participants n=4 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=5 Participants
PANSS total score	102.3 units on a scale STANDARD_DEVIATION 12 • n=7 Participants	101.6 units on a scale STANDARD_DEVIATION 11.95 • n=5 Participants	100.3 units on a scale STANDARD_DEVIATION 11.54 • n=4 Participants	98.1 units on a scale STANDARD_DEVIATION 10.78 • n=5 Participants
CGI-S score	4.8 units on a scale STANDARD_DEVIATION 0.57 • n=7 Participants	4.9 units on a scale STANDARD_DEVIATION 0.55 • n=5 Participants	4.82 units on a scale STANDARD_DEVIATION 0.59 • n=4 Participants	4.8 units on a scale STANDARD_DEVIATION 0.64 • n=5 Participants

PRIMARY outcome

Timeframe: From Randomization to Week 8

Population: 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

Outcome measures

Outcome measures
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=27 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=31 Participants Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score	-4.71 units on a scale Standard Error 2.22	-10.19 units on a scale Standard Error 2.16

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=27 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=31 Participants Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score	-0.18 units on a scale Standard Error 0.12	-0.37 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=27 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=31 Participants Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score	-2.99 units on a scale Standard Error 1.64	-3.14 units on a scale Standard Error 1.58

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=27 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=31 Participants Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Change From Randomization to Week 8 in PANSS Marder Negative Factor Score	-1.51 units on a scale Standard Error 0.77	-1.74 units on a scale Standard Error 0.75

SECONDARY outcome

Timeframe: at Week 8

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

Outcome measures

Outcome measures
Measure	Double-blind Treatment (DBT) Period, Lu AF35700 10 mg n=27 Participants Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT, Continued Treatment From PC Period n=31 Participants Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
Response	6 Participants	13 Participants

Adverse Events

Prospective Confirmation (PC) Period - Risperidone

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

PC Period - Olanzapine

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Double Blind Treatment (DBT) Period - Lu AF35700 10 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

DBT Period, Continued Treatment From PC Period

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Prospective Confirmation (PC) Period - Risperidone n=68 participants at risk Patients not randomized to double-blind treatment	PC Period - Olanzapine n=51 participants at risk Patients not randomized to double-blind treatment	Double Blind Treatment (DBT) Period - Lu AF35700 10 mg n=35 participants at risk Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT Period, Continued Treatment From PC Period n=33 participants at risk 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).
Psychiatric disorders Suicidal ideation	1.5% 1/68 • Number of events 1 • 20 weeks	0.00% 0/51 • 20 weeks	0.00% 0/35 • 20 weeks	0.00% 0/33 • 20 weeks
Vascular disorders Hypertension	0.00% 0/68 • 20 weeks	2.0% 1/51 • Number of events 1 • 20 weeks	0.00% 0/35 • 20 weeks	0.00% 0/33 • 20 weeks

Other adverse events

Other adverse events
Measure	Prospective Confirmation (PC) Period - Risperidone n=68 participants at risk Patients not randomized to double-blind treatment	PC Period - Olanzapine n=51 participants at risk Patients not randomized to double-blind treatment	Double Blind Treatment (DBT) Period - Lu AF35700 10 mg n=35 participants at risk Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks	DBT Period, Continued Treatment From PC Period n=33 participants at risk 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).
Investigations Weight increased	1.5% 1/68 • Number of events 1 • 20 weeks	0.00% 0/51 • 20 weeks	2.9% 1/35 • Number of events 1 • 20 weeks	9.1% 3/33 • Number of events 3 • 20 weeks
Nervous system disorders Akathisia	5.9% 4/68 • Number of events 4 • 20 weeks	0.00% 0/51 • 20 weeks	0.00% 0/35 • 20 weeks	0.00% 0/33 • 20 weeks
Psychiatric disorders Anxiety	8.8% 6/68 • Number of events 7 • 20 weeks	2.0% 1/51 • Number of events 1 • 20 weeks	11.4% 4/35 • Number of events 4 • 20 weeks	3.0% 1/33 • Number of events 1 • 20 weeks
Psychiatric disorders Insomnia	5.9% 4/68 • Number of events 4 • 20 weeks	0.00% 0/51 • 20 weeks	2.9% 1/35 • Number of events 1 • 20 weeks	6.1% 2/33 • Number of events 2 • 20 weeks
Psychiatric disorders Schizophrenia	1.5% 1/68 • Number of events 1 • 20 weeks	3.9% 2/51 • Number of events 2 • 20 weeks	5.7% 2/35 • Number of events 2 • 20 weeks	3.0% 1/33 • Number of events 1 • 20 weeks

Additional Information

Email contact via

H. Lundbeck A/S

Phone: +4536301311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place