Trial Outcomes & Findings for Efficacy of an Early Antipsychotic Switch in Case of Poor Initial Response to the Treatment of Schizophrenia (NCT NCT01029769)

Last Updated: 2024-10-21

Results Overview

Remission is defined as a maximum rating of 3 points (equals a severity rating of "mild") in each of all the following eight items of the PANSS (Kay et al.) rating scale: Delusions (P1), unusual thought content (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (N1), social withdrawal (N4) and lack of spontaneity (N6); if one item is \>3 the remission status is "no" (non-remission); all times have a rating from 1 to 7, so the min. rating is 8, the max. rating is 56. Remission is a dichotomous item (yes/no) without a specific min. or max. rating

Recruitment status

COMPLETED

Study phase

Target enrollment

350 participants

Primary outcome timeframe

8 weeks

Results posted on

2024-10-21

Participant Flow

The enrollment at baseline comprises the periods "initial olanzapine" and "initial amisulpride"; a re-randomisation was performed after 2 weeks of treatment; the patient numbers in the second phase of the trial must not be added to the overall participant number at baseline (other three groups all formed in phase II of the trial); NOTE that the groups "early responders", "early non-responders switched", "early non-responders non-switched" become active only in phase II of the trial, not before!!

Participant milestones

Participant milestones
Measure	Initial Olanzapin Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Initial Amisulpride Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Early Responders Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Early Non-responders Switched Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Ealy Non-responders Non-switched Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Period 1: Initial 2-week Treatment STARTED	163	164	0	0	0
Period 1: Initial 2-week Treatment COMPLETED	140	145	0	0	0
Period 1: Initial 2-week Treatment NOT COMPLETED	23	19	0	0	0
Period 2: Extended 6-week Treatment STARTED	0	0	140	70	72
Period 2: Extended 6-week Treatment COMPLETED	0	0	104	60	55
Period 2: Extended 6-week Treatment NOT COMPLETED	0	0	36	10	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of an Early Antipsychotic Switch in Case of Poor Initial Response to the Treatment of Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Period 1: Initital 2-week Treatment - Amisulpride n=163 Participants Baseline assessment of period 1 of all patients randomised to amisulpride flexible 200-800 mg/d double blind treatment	Period 1: Initital 2-week Treatment - Olanzapine n=164 Participants Baseline assessment of period 1 of all patients randomised to olanzapine flexible 5-20 mg/d double blind treatment	Total n=327 Participants Total of all reporting groups
Age, Continuous	40.3 years STANDARD_DEVIATION 12.1 • n=5 Participants	39.3 years STANDARD_DEVIATION 10.9 • n=7 Participants	39.8 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	79 Participants n=7 Participants	154 Participants n=5 Participants
Sex: Female, Male Male	88 Participants n=5 Participants	85 Participants n=7 Participants	173 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	163 Participants n=5 Participants	164 Participants n=7 Participants	327 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
Region of Enrollment Germany	75 Participants n=5 Participants	75 Participants n=7 Participants	150 Participants n=5 Participants
Region of Enrollment Romania	88 Participants n=5 Participants	89 Participants n=7 Participants	177 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: please note that all patients, regardless of the medication received, were combined in these groups for the primary endpoint analysis solely depending on whether they have met the criteria for "early non-response" at the end of phase I of the trial; so the statistical analysis does not follow the treatment arms in phase I of the trial (patients received alternatively olanzapine or amisulpride, but both types of treatment appear in one and the same analysis group!)

Outcome measures

Outcome measures
Measure	Early Non-responders Switched n=60 Participants Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Early Non-responders Non-switched n=55 Participants Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Number of Patients in Symptomatic Remission at Week 8 Comparing the "Switched" With the "Non Switched" Early Non-responders	41 Participants	25 Participants

SECONDARY outcome

Timeframe: 8 weeks

The Positive and Negative Syndrome Scale (Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bull 1987; 13:261-276) is a 30- item inventory assessing the absence or severity of schizophrenia symptoms across three subscales: positive symptoms (items P1-P7, including hallucinatory behavior, delusions, and conceptual disorganization), negative symptoms (items N1-N7, including blunted affect, social and emotional withdrawal, and lack of spontaneity), and general psychopathology symptoms (items G1-G16, including mannerisms and posturing, unusual thought content, and lack of insight). Each item is scored on a scale ranging from 1 (absent) to 7 (extreme), with item ratings incorporating the presence, effects of symptoms on an individuum's thinking, feeling or behaving as well as their severity. The min. sum rating is 30, the max. sum rating is 210.

Outcome measures

Outcome measures
Measure	Early Non-responders Switched n=60 Participants Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding	Early Non-responders Non-switched n=55 Participants Olanzapine or amisulpride: Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
PANSS Total Score Change	-22.8 units on a scale Standard Deviation 19.9	-17.3 units on a scale Standard Deviation 15.1

Adverse Events

Period 1: Initital 2-week Treatment - Amisulpride Treated Patients

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Period 1: Initital 2-week Treatment - Olanzapine Treated Patients

Serious events: 3 serious events

Other events: 33 other events

Deaths: 1 deaths

Period 2: Extended 6-week Treatment - Early Responders

Serious events: 7 serious events

Other events: 32 other events

Deaths: 1 deaths

Period 2: Extended 6-week Treatment - Early Non-responders Switched

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Period 2: Extended 6-week Treatment - Early Non-responders Not Switched

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Period 1: Initital 2-week Treatment - Amisulpride Treated Patients n=163 participants at risk oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 1: Initital 2-week Treatment - Olanzapine Treated Patients n=164 participants at risk oral olanzapine 5mg to 20mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Responders n=140 participants at risk double blind continuation of treatment as in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Non-responders Switched n=70 participants at risk double blind switch to the alternative drug not used in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Non-responders Not Switched n=72 participants at risk double blind continuation of treatment as in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding
Nervous system disorders prolongation of hospitalisation	1.8% 3/163 • Number of events 3 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/164 • Entire 8 weeks of treatment spontaneous reporting	0.71% 1/140 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/70 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/72 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting
Psychiatric disorders hospitalisation	0.00% 0/163 • Entire 8 weeks of treatment spontaneous reporting	0.61% 1/164 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	4.3% 6/140 • Number of events 6 • Entire 8 weeks of treatment spontaneous reporting	2.9% 2/70 • Number of events 2 • Entire 8 weeks of treatment spontaneous reporting	4.2% 3/72 • Number of events 3 • Entire 8 weeks of treatment spontaneous reporting
Respiratory, thoracic and mediastinal disorders life threatening event	0.00% 0/163 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/164 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/140 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/70 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/72 • Entire 8 weeks of treatment spontaneous reporting
Injury, poisoning and procedural complications life threatening event	0.00% 0/163 • Entire 8 weeks of treatment spontaneous reporting	0.61% 1/164 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/140 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/70 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/72 • Entire 8 weeks of treatment spontaneous reporting
Hepatobiliary disorders death	0.00% 0/163 • Entire 8 weeks of treatment spontaneous reporting	0.61% 1/164 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/140 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/70 • Entire 8 weeks of treatment spontaneous reporting	0.00% 0/72 • Entire 8 weeks of treatment spontaneous reporting

Other adverse events

Other adverse events
Measure	Period 1: Initital 2-week Treatment - Amisulpride Treated Patients n=163 participants at risk oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 1: Initital 2-week Treatment - Olanzapine Treated Patients n=164 participants at risk oral olanzapine 5mg to 20mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Responders n=140 participants at risk double blind continuation of treatment as in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Non-responders Switched n=70 participants at risk double blind switch to the alternative drug not used in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding	Period 2: Extended 6-week Treatment - Early Non-responders Not Switched n=72 participants at risk double blind continuation of treatment as in period 1; oral olanzapine 5mg to 20mg/d; OR oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding
Musculoskeletal and connective tissue disorders akathisia	6.1% 10/163 • Number of events 10 • Entire 8 weeks of treatment spontaneous reporting	1.2% 2/164 • Number of events 2 • Entire 8 weeks of treatment spontaneous reporting	5.0% 7/140 • Number of events 7 • Entire 8 weeks of treatment spontaneous reporting	4.3% 3/70 • Number of events 3 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/72 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting
Musculoskeletal and connective tissue disorders tremor	6.1% 10/163 • Number of events 10 • Entire 8 weeks of treatment spontaneous reporting	4.3% 7/164 • Number of events 7 • Entire 8 weeks of treatment spontaneous reporting	5.7% 8/140 • Number of events 8 • Entire 8 weeks of treatment spontaneous reporting	5.7% 4/70 • Number of events 4 • Entire 8 weeks of treatment spontaneous reporting	2.8% 2/72 • Number of events 2 • Entire 8 weeks of treatment spontaneous reporting
Metabolism and nutrition disorders weight increase	4.3% 7/163 • Number of events 7 • Entire 8 weeks of treatment spontaneous reporting	7.3% 12/164 • Number of events 12 • Entire 8 weeks of treatment spontaneous reporting	2.9% 4/140 • Number of events 4 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/70 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/72 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting
Nervous system disorders headache	1.8% 3/163 • Number of events 3 • Entire 8 weeks of treatment spontaneous reporting	2.4% 4/164 • Number of events 4 • Entire 8 weeks of treatment spontaneous reporting	4.3% 6/140 • Number of events 6 • Entire 8 weeks of treatment spontaneous reporting	5.7% 4/70 • Number of events 4 • Entire 8 weeks of treatment spontaneous reporting	1.4% 1/72 • Number of events 1 • Entire 8 weeks of treatment spontaneous reporting
Nervous system disorders Insomnia	3.7% 6/163 • Number of events 6 • Entire 8 weeks of treatment spontaneous reporting	4.9% 8/164 • Number of events 8 • Entire 8 weeks of treatment spontaneous reporting	5.0% 7/140 • Number of events 7 • Entire 8 weeks of treatment spontaneous reporting	12.9% 9/70 • Number of events 9 • Entire 8 weeks of treatment spontaneous reporting	2.8% 2/72 • Number of events 2 • Entire 8 weeks of treatment spontaneous reporting

Additional Information

Prof. Dr. Dr. Stefan Leucht

Technische Universitaet Muenchen, Germany

Phone: +498941404200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place