E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the treatment effect of AMG 747 compared to placebo on negative symptoms as measured by the Negative Symptom Assessment Scale (NSA-16) in patients with schizophrenia stabilized with ongoing antipsychotic therapy |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of AMG 747 on the proportion of subjects achieving clinically meaningful improvement from baseline, as defined by a ≥ 20% decrease from baseline on negative symptoms as measured by the NSA-16;
- To evaluate the effect of AMG 747 on symptoms of schizophrenia as measured by the PANSS total score and Marder factor scores;
- To evaluate the effect of AMG 747 on global change as measured by the CGI-S and CGI-I scales;
- To evaluate the effect of AMG 747 on cognitive function as measured by the CogState Schizophrenia Battery;
- To evaluate the effect of AMG 747 on everyday functioning as measured by the PSP scale;
- To evaluate the effect of AMG 747 on PROs as measured by the Q-LES-Q-18 and SDS;
- To evaluate safety and tolerability of AMG 747. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Pharmacokinetic (PK) sub-study, 21 October 2011: This sub-study will be carried out on a subset of approximately 90 subjects (approximately 20 subjects per AMG 747 treatment group) at selected sites. These subjects will be required to sign an additional optional informed consent to participate in this sub-study. The PK sub-study enrollment will be blinded; however, the PK samples will be analyzed only for those subjects assigned to an AMG 747 treatment group. PK sub-study enrollment will close once the target number of PK sub-study participants has been reached. PK sub-study subjects will have additional blood samples collected at 1.5, 4 and 24 hours post-dose at baseline/day 1 (ie, after first IMP dose) and at 0.5 and 2 hours post-dose at week 4. The purpose of this sub-study is to evaluate the pharmacokinetic profile of AMG 747 when given as a daily oral dose in subjects with schizophrenia stabilized with ongoing antipsychotic therapy.
- Pharmacogenetic sub-study, 21 October 2011: If a subject signs the additional optional informed consent (Pharmacogenetic Consent), DNA extracted from the cell pellets from pre-dose PK plasma samples on baseline/day 1, week 4 and week 8 may be analyzed for optional, exploratory pharmacogenetic analyses.
These optional analyses focus on inherited genetic variations, to evaluate their possible correlation to the disease and/or responsiveness to the therapies used in this study. The goals of these optional studies include the use of genetic markers to help in the investigation of neuropsychiatric disorders such as schizophrenia and/or to identify subjects who may respond positively or negatively to AMG 747. |
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E.3 | Principal inclusion criteria |
- Adults, 18-60 years of age upon entry into screening;
- Diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia;
- Total score on the PANSS Marder Negative Symptom Factor Scale (NSFS) ≥ 20, Total score on the PANSS Marder Positive Symptom Factor
Scale (PSFS) ≤ 30;
- Receiving stable antipsychotic therapy for at least 8 weeks prior to screening;
- Receiving a stable dose of other psychotropic agents for at least 8 weeks prior to screening;
- Subject has had a stable residence or living arrangement for at least 8 weeks prior to screening and the residence or living arrangement is not anticipated to change for the duration of the study;
- Subject or subject's legally acceptable representative has provided informed consent. |
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E.4 | Principal exclusion criteria |
- Current schizoaffective disorder, bipolar disorder, panic disorder or obsessive
compulsive disorder, or evidence of mental retardation by history or clinical
examination or known premorbid IQ ≤ 70;
- Clinically significant suicidal ideation or suicide attempts, assaultive behavior or marked changes in mood within the 8 weeks prior to screening, or current active suicidal ideation in clinical exam;
- Substance abuse (with the exception of nicotine or caffeine abuse) within the 8 weeks prior to screening, or during screening;
- Substance dependence (with the exception of nicotine or caffeine dependence) within the 6 months prior to screening or during screening;
- Planning to initiate a smoking cessation therapy or otherwise substantially modify nicotine use during the study;
- Positive urine drug test for substances of abuse (with the exception of positive screens for prescribed agents such as benzodiazepines). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to week 12 in negative symptoms, as measured by the NSA-16 total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Response defined as a ≥ 20% decrease in the NSA-16 total score at week 12;
- Change from baseline to week 12 on the PANSS total score and Marder factor scores (positive, negative, disorganized thought, hostility/excitement, anxiety/depression symptoms);
- Change from baseline to week 12 on the CGI-S;
- CGI-I scores at week 12;
- Change from baseline to week 12 on the CogState;
- Change from baseline to week 12 on the PSP;
- Change from baseline to week 12 on the Q-LES-Q-18 and SDS;
Safety Endpoints:
- Adverse events;
- Clinical laboratory values and vital signs;
- 12-lead ECG;
- Calgary Depression Scale for Schizophrenia (CDSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
European Union |
Malaysia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The time when the last subject completes the last study visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |