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The main aim of the trial is to study whether a change of medication in non-responders to a two-weeks antipsychotic drug trial is more effective than continued treatment with the same antipsychotic. Hypothesis: Non-responders who are switched at 2 weeks to another antipsychotic are more frequently in symptomatic remission at week 8 than non-responders who stay on the same antipsychotic
The patients will be randomised to a double-blind 2 week run in phase with fixed doses of either oral amisulpride 800 mg/day or olanzapine 20mg/day.
Those participants who have not responded to treatment at two weeks (PANSS improvement <25%) will be randomised to a 6 week double blind flexible dose phase:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| initial olanzapine | Active Comparator |
| |
| initial amisulpride | Active Comparator |
| |
| early responders | Active Comparator |
| |
| early non-responders switched | Active Comparator |
| |
| ealy non-responders non-switched | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olanzapine or amisulpride | Drug | Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients in Symptomatic Remission at Week 8 Comparing the "Switched" With the "Non Switched" Early Non-responders | 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 | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| PANSS Total Score Change | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stefan Leucht, MD | Psychiatrische Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Universität München am Klinikum rechts der Isar | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Psychiatrische Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Universitaet Muenchen am Klinikum rechts der Isar | Munich | Bavaria | 81675 | Germany |
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!!
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Initial 2-week Treatment |
| |||||||||||||
| Period 2: Extended 6-week Treatment |
|
Three hundred and twenty-seven patients were randomized in study phase I.
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| ID | Title | Description |
|---|---|---|
| BG000 | Period 1: Initital 2-week Treatment - Amisulpride | Baseline assessment of period 1 of all patients randomised to amisulpride flexible 200-800 mg/d double blind treatment |
| BG001 | Period 1: Initital 2-week Treatment - Olanzapine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients in Symptomatic Remission at Week 8 Comparing the "Switched" With the "Non Switched" Early Non-responders | 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 | 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!) | Posted | Count of Participants | Participants | 8 weeks |
Entire 8 weeks of treatment
spontaneous reporting
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period 1: Initital 2-week Treatment - Amisulpride Treated Patients | oral amisulpride 200mg to 800mg/d; preferably once daily, encapsulated for blinding |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| prolongation of hospitalisation | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| akathisia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
Patients with poor response to antipsychotic treatment in the past (treatment resistant patients) were not excluded by definition from study participation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Dr. Stefan Leucht | Technische Universitaet Muenchen, Germany | +498941404200 | stefan.leucht@tum.de |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077152 | Olanzapine |
| D000077582 | Amisulpride |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| 8 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
Baseline assessment of period 1 of all patients randomised to olanzapine flexible 5-20 mg/d double blind treatment
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | 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 |
| OG001 | Early 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 |
|
|
|
| Secondary | PANSS Total Score Change | 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. | Posted | Mean | Standard Deviation | units on a scale | 8 weeks |
|
|
|
| 0 |
| 163 |
| 3 |
| 163 |
| 36 |
| 163 |
| EG001 | Period 1: Initital 2-week Treatment - Olanzapine Treated Patients | oral olanzapine 5mg to 20mg/d; preferably once daily, encapsulated for blinding | 1 | 164 | 3 | 164 | 33 | 164 |
| EG002 | Period 2: Extended 6-week Treatment - Early Responders | 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 | 1 | 140 | 7 | 140 | 32 | 140 |
| EG003 | Period 2: Extended 6-week Treatment - Early Non-responders Switched | 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 | 0 | 70 | 5 | 70 | 21 | 70 |
| EG004 | Period 2: Extended 6-week Treatment - Early Non-responders Not Switched | 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 | 0 | 72 | 4 | 72 | 7 | 72 |
| hospitalisation | Psychiatric disorders | Non-systematic Assessment |
|
| life threatening event | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| life threatening event | Injury, poisoning and procedural complications | Non-systematic Assessment | suicide attempt |
|
| life threatening event | Injury, poisoning and procedural complications | Non-systematic Assessment | lithium intoxication |
|
| death | Hepatobiliary disorders | Non-systematic Assessment | acute cholecystitis |
|
| tremor | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| weight increase | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| headache | Nervous system disorders | Non-systematic Assessment |
|
| Insomnia | Nervous system disorders | Non-systematic Assessment |
|
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| D006571 | Heterocyclic Compounds |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |