| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Dementia of the Alzheimer's type (DSM-IV TR) code 294.11 |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Classification code | 10012271 |
|
| 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 |
| The primary objective of this study is to investigate the safety and efficacy of bifeprunox (5 to 15 mg/day) compared with placebo in the treatment of psychosis and behavioral disturbances associated with dementia of the Alzheimer's type in elderly subjects. Patient safety and tolerability, as well as the change from baseline to endpoint in the Brief Psychiatric Rating Scale (BPRS) will be the primary outcome measures. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives will investigate the efficacy of bifeprunox using the
Neuropsychiatric Inventory (NPI-NH), Clinical Global Impression (CGI) scale and the Cohen-Mansfield Agitation Inventory (CMAI). Safety and tolerability will be assessed by adverse events, clinical laboratory evaluation, concomitant medications, abnormal movement assessments, physical examinations including vital signs; and ECGs. The pharmacokinetics of bifeprunox will also be explored in the studied patient population.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Current Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text
Revision (DSM-IV TR) diagnosis of Dementia of the Alzheimer.s Type (code 294.11);
In order to be eligible to participate in this study, subjects must meet the following criteria:
1. Delusions or Hallucinations ≥1 month, at least moderate in severity (i.e. impair
subjects. functional capacity or cause them to pose a threat to themselves).
2. Fulfill the criteria for behavioral disturbance. defined as: A score of greater than 3 on any one of the following BPRS items:
- Hostility,
- Suspiciousness,
- Uncooperativeness (hostile-suspiciousness factor);
Or a score of greater than 6 on the sum of these three items;
3. The subject's authorized Legal Representative must understand the nature of the study and must provide written informed consent with the subject assent or based on country specific laws the subject's next of kin must provide concent/assent prior to the conduct of any study procedures (including any changes occurring in the subject's current therapeutic regimen);
4. Each subject must be able to speak, read, understand and possess the ability to follow simple instructions in English or in their native language if the Investigator is fluent in that language. All required documents, including the informed consent, will be translated into that language as appropriate;
5. Male or female subject's ≥ 65, but ≤ 90 years of age.
|
|
| E.4 | Principal exclusion criteria |
1. Current evidence of clinically significant, untreated or uncontrolled neurological, hematological, immunological, endocrine, cardiovascular, hepatic, renal, gastrointestinal, pulmonary or infectious disease, or metabolic disturbance that would possibly interfere with the subject's participation in the study. Patients with evidence of stroke, hepatitis or head trauma should be excluded;
2. Subjects with other current Axis I primary psychiatric diagnoses that may interfere with the interpretation of efficacy and/or safety evaluations, e.g., Bipolar Disorder, Schizophrenia or Schizoaffective Disorder. Patients with current depressive and
anxiety disorders may be considered on a case-by-case basis.
3. Any clinically significant abnormal laboratory data (e.g., creatinine, aspartate
transaminase (AST) or alanine transaminase (ALT) greater than 2X the upper limit of normal), vital sign, physical examination at screening or baseline which in the opinion of the Investigator would preclude study participation or interfere with the assessment of safety;
4. Vascular dementia or dementia due to substance abuse, head trauma, or HIV disease;
5. History of seizure disorder requiring treatment within the previous 12 months;
6. Current alcohol or drug dependence (DSM-IV TR. criteria), or history of substance abuse within the past year;
7. Clinical or radiological evidence of stroke;
8. Subjects with uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension by history or physical exam, defined as a decrease of 30 mmHg or more in systolic BP and/or a decrease of 20 mmHg or more in diastolic BP after at least two minutes standing compared to the previous lying BP. The abnormal value must be confirmed at two separate measurements;
9. Subjects who experience significant difficultly ingesting oral medications as well as patients with clinically significant dysphagia, esophageal motility disorders, hiatal hernia, or esophageal stricture.
10. History of multiple episodes of aspiration pneumonia (≥ 2) in the 90 days prior to the baseline visit.
11. Subjects with clinically significant abnormal ECG findings, including clinically
relevant conduction disturbances identified at screening. These include subjects with any one or more of the following:
-Subjects with a cardiac pacemaker at screening or who require the implantation of a pacemaker during the study;
- Subjects with clinically significant (or potentially clinically significant) abnormal ECG findings that are present at screening or that are identified any time throughout the study, including: atrial fibrillation / flutter, prolonged QTc using Bazett’s formula (> 450 msecs for men and > 470 msecs for women), complex premature ventricular contractions, other clinically relevant conduction disturbances, incomplete right bundle branch blocks, potentially clinically significant ST/T wave changes.
Subjects with first degree A-V block can be allowed in the trial on a case-by-case basis following review with the Quintiles Medical Advisor)
12. History of repeated vasovagal syncope;
13. Clinical evidence of Parkinson.s disease, Lewy body disease, Huntington’s disease, tardive dyskinesia, or multiple sclerosis;
14. Subjects judged by the Investigator as being at significant risk of suicide and/or
violent behavior;
15. Subjects receiving a depot antipsychotic medication within one dose interval prior to Screening;
16. Subjects who, in the Investigator.s opinion, have failed to respond to adequate
courses of treatment (with reference to dose and duration) with two or more
antipsychotic medications which belong to different classes;
17. Exposure to any investigational drug within 60 days prior to Baseline (Day 1);
18. Subjects who have received electroconvulsive therapy (ECT) within 90 days prior to Baseline (Day 1);
19. Known hypersensitivity or contraindication to the use of serotonergic agents,
dopamine antagonists or dopamine agonists. Severe drug allergy or any history of
severe abnormal drug reaction;
20. Subjects unable to discontinue all antipsychotic medication at least three days prior to baseline;
21. Prior exposure to bifeprunox;
22. Subjects treated with clozapine within 60 days prior to Baseline (Day 1);
23. Uncorrected hypothyroidism or hyperthyroidism;
24. Subjects who need treatment with anticholinergic drugs (use of an anticholinergic
drug for the treatment of EPS emerging during the study will be permitted as
required);
25. Subjects who have experienced neuroleptic malignant syndrome;
26. Site personnel and their immediate families, defined as their spouse, parent, child,grandparent or grandchild;
27. Reasonable likelihood for non-compliance with the protocol or any other reason that in the Investigator's opinion, prohibits the inclusion of the subject into the study
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measurement will be the change from baseline to endpoint in the brief psychological rating scale (BPRS) with LOCF algorithm. The secondary efficacy measurements will include the Neuropsychiatric Inventory (NPI-NH), the Clinical Global Impression severity (CGI-S) and improvement (CGI-I) scale and the Cohen-Mansfield Agitation Inventory (CMAI). |
|
| 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 | No |
| 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 | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| The end of treatment of the last patient. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 17 |
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