/A
- Conditions
- Alzheimer's diseaseMedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease
- Registration Number
- EUCTR2009-011799-31-IE
- Lead Sponsor
- Medivation, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1.Are men and women = 50 years of age with probable AD judged to be moderate-to-severe (based on a Screening MMSE of 5 to 14, inclusive) and who are diagnosed according to the following criteria:
a.Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision (DSM-IV-TR) as listed in Appendix A;
b.National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer’s Disease and Related Disorder Association’s Criteria (NINCDS-ADRDA) for probable AD as listed in Appendix B;
c.MMSE score between 5 and 14, inclusive;
d.Modified Hachinski Ischemic Score = 4 (Appendix C);
2.Have either:
a.NPI score = 6 on the domains of delusions and hallucinations, with delusions and/or visual or auditory hallucinations present at least intermittently for a minimum of four weeks; or
b.NPI total score = 15 without delusions and hallucinations and a CMAI score = 15;
3.Have symptoms of delusions and/or hallucinations, if present, that developed after the onset of dementia and that are judged by the investigator and caregiver to be severe enough to disrupt the patient’s and/or other’s functioning;
4.Are willing and able to give informed consent. If, and only if, the patient is not competent, a mentally-competent legally-acceptable representative must provide informed consent on his/her behalf, and the patient must provide assent, if appropriate per local ethics committee judgment and consistent with local laws;
5.Have had brain imaging such as computed tomography (CT) and/or magnetic resonance imaging (MRI) within 12 months of enrollment, consistent with a diagnosis of probable AD without any other clinically significant co-morbid pathologies found. If there has been a significant change in clinical status suggestive of stroke or other possible central nervous system disease as assessed by the investigator with onset between the time of the last CT or MRI and the Screening visit, the scan should be repeated;
6.Have been taking the cholinesterase inhibitor, donepezil, for at least six months, with stable dosing at 5 or 10 mg/day for at least the last four months prior to Screening (and with no intent to change for the duration of the study);
7.Ambulatory and permitted to use an assistance device (e.g., walker or cane);
8.Were previously (in pre-AD condition) capable of reading, writing, and communicating effectively with others;
9.Have a caregiver who assists (or directly supervises) the patient at least five days per week for at least three hours per day and has intimate knowledge of the patient’s cognitive, functional, and emotional states, and of the patient’s personal care. The caregiver must be willing to accompany the patient to all study visits, supervise study drug administration, and (in addition to the patient) report adverse events. The caregiver must be willing and able to give informed consent, be able to read and write, and be capable of providing responses to the NPI, ADCS ADLsev, CIBIC-plus, RUD Lite©, and EQ-5D assessment tools;
10.Living in the community (not under 24-hour supervision in a nursing home or institution);
11.If female, is either a) of reproductive potential and compliant in using adequate birth control or b) not of reproductive potential. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception (hormone-based, intrauterine device, or double barrier contraception, i.e., condom and diaphragm, diaphragm and spermicidal gel or foam;
1.Are men and women = 50 years of age with probable AD judged to be moderate-to-severe (based on a Screening MMSE of 5 to 14, inclusive) and who are diagnosed according to the following criteria:
a.Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision (DSM-IV-TR) as listed in Appendix A;
b.National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer’s Disease and Related Disorder Association’s Criteria (NINCDS-ADRDA) for probable AD as listed in Appendix B;
c.MMSE score between 5 and 14, inclusive;
d.Modified Hachinski Ischemic Score = 4 (Appendix C);
2.Have either:
a.NPI score = 6 on the domains of delusions and hallucinations, with delusions and/or visual or auditory hallucinations present at least intermittently for a minimum of four weeks; or
b.NPI total score = 15 without delusions and hallucinations and a CMAI score = 15;
3.Have symptoms of delusions and/or hallucinations, if present, that developed after the onset of dementia and that are judged by the investigator and caregiver to be severe enough to disrupt the patient’s and/or other’s functioning;
4.Are willing and able to give informed consent. If, and only if, the patient is not competent, a mentally-competent legally-acceptable representative must provide informed consent on his/her behalf, and the patient must provide assent, if appropriate per local ethics committee judgment and consistent with local laws;
5.Have had brain imaging such as computed tomography (CT) and/or magnetic resonance imaging (MRI) within 12 months of enrollment, consistent with a diagnosis of probable AD without any other clinically significant co-morbid pathologies found. If there has been a significant change in clinical status suggestive of stroke or other possible central nervous system disease as assessed by the investigator with onset between the time of the last CT or MRI and the Screening visit, the scan should be repeated;
6.Have been taking the cholinesterase inhibitor, donepezil, for at least six months, with stable dosing at 5 or 10 mg/day for at least the last four months prior to Screening (and with no intent to change for the duration of the study);
7.Ambulatory and permitted to use an assistance device (e.g., walker or cane);
8.Were previously (in pre-AD condition) capable of reading, writing, and communicating effectively with others;
9.Have a caregiver who assists (or directly supervises) the patient at least five days per week for at least three hours per day and has intimate knowledge of the patient’s cognitive, functional, and emotional states, and of the patient’s personal care. The caregiver must be willing to accompany the patient to all study visits, supervise study drug administration, and (in addition to the patient) report adverse events. The caregiver must be willing and able to give informed consent, be able to read and write, and be capable of providing responses to the NPI, ADCS ADLsev, CIBIC-plus, RUD Lite©, and EQ-5D assessment tools;
10.Living in the community (not under 24-hour supervision in a nursing home or institution);
11.If female, is either a) of reproductive potential and compliant in using adequate birth control or b) not of reproductive potential. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception (hormone-based, intrauterine device, or double barrier contraception, i.e., condom and diaphragm, diaphragm and spermicidal gel or foam
1. Have major structural brain disease;
2. Have any major medical illness or unstable medical condition w/in 6 mos of Screening that may interfere with the patient’s ability to comply with study procedures & abide by study restrictions, or with the ability to interpret safety data, including: Any physical disability that would prevent completion of study procedures or assessments;
A history of cancer within 5 yrs of enrollment with the exception of non melanoma skin cancers or prostate cancer that has been stable for at least 6 mos; The following cardiovascular parameters:
•Hypotension or bradycardia with heart rate < 50 bpm at Screening or on more than one occasion w/in 3 mos prior to enrollment;
•Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening or on more than 1 occasion within 3 mos prior to enrollment;
•A QTcF of > 470 msec on an ECG at Screening;
•Active cardiovascular disease;
d. A history of traumatic brain injury with residual neurological deficit or stroke;
e. A diagnosis of a CNS disease other than AD;
f. A history of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness w/in 6 mos prior to enrollment;
g. Symptoms of delusions and hallucinations that are better accounted for by another general-medical or psychiatric condition or by direct physiological effects of a substance;
h. Symptoms of agitation and aggression that can be better explained by another medical or psychiatric condition, medication, or substance abuse;
i. Meeting DSM-IV-TR criteria for schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features;
j. Any current psychiatric diagnosis according to DSM-IV-TR that may interfere with the patient’s ability to perform the study and all assessments;
3. Are pregnant or breastfeeding females;
4. Reside in a nursing home or institution where s/he is receiving 24-hr supervision;
5. Have a caregiver who is not clinically trained and is paid to care for more than 2 patients;
6. Have known HIV seropositivity;
7. Have any of the following laboratory abnormalities at Screening:
a. Clinically significant Vitamin B12 levels < the lower limit of normal (LLN) or on replacement Vitamin B12 for < 3 mos prior to enrollment;
b. Clinically significant folate levels < the LLN or on replacement folate therapy for < 3 mos prior to enrollment;
c. TSH levels > the ULN AND a free thyroxine level lower than the LLN;
d. Positive Rapid Plasma Reagin confirmed by Fluorescent Treponemal Antibody - Absorption;
e. Total bilirubin, ALT or AST > 2 times the ULN;
f. Renal impairment with a serum creatinine > 133 µmol/L (1.5 mg/dL);
g. Hematocrit < 37% for males or < 32% for females, absolute neutrophil cell count of less than or equal to 1,500/ µL, or platelet cell count of < 120,000/µL;
8. Have taken or plan to take a cholinesterase inhibitor other than donepezil within 6 mos prior to Screening through the end of study;
9. Have taken or plan to take memantine within 90 days prior to Screening through the end of study;
10. Have taken or plan to take a prescription medical food or prescription nutriceutical marketed for AD or cognitive impairment within 30 days of Screening through the end of study;
11. Have a history of hypersensitivity to Dimebon or other antihistamines;
12. Have used non-selective antihistamines within 7 days prior to the start of dosing;
13. Have used ;
1. Have major structural brain disease;
2. Have any major medical illness or unstable medical condition w/in 6 mos of Screening that may interfere with the patient’s ability to comply with study procedures & abide by study restrictions, or with the ability to interpret safety data, including: Any physical disability that would prevent completion of study procedures or assessments;
A history of cancer within 5 yrs of enrollment with the exception of non melanoma skin cancers or prostate cancer that has been stable for at least 6 mos; The following cardiovascular parameters:
•Hypotension or bradycardia with heart rate < 50 bpm at Screening or on more than one occasion w/in 3 mos prior to enrollment;
•Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening or on more than 1 occasion within 3 mos prior to enrollment;
•A QTcF of > 470 msec on an ECG at Screening;
•Active cardiovascular disease;
d. A history of traumatic brain injury with residual neurological deficit or stroke;
e. A diagnosis of a CNS disease other than AD;
f. A history of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness w/in 6 mos prior to enrollment;
g. Symptoms of delusions and hallucinations that are better accounted for by another general-medical or psychiatric condition or by direct physiological effects of a substance;
h. Symptoms of agitation and aggression that can be better explained by another medical or psychiatric condition, medication, or substance abuse;
i. Meeting DSM-IV-TR criteria for schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features;
j. Any current psychiatric diagnosis according to DSM-IV-TR that may interfere with the patient’s ability to perform the study and all assessments;
3. Are pregnant or breastfeeding females;
4. Reside in a nursing home or institution where s/he is receiving 24-hr supervision;
5. Have a caregiver who is not clinically trained and is paid to care for more than 2 patients;
6. Have known HIV seropositivity;
7. Have any of the following laboratory abnormalities at Screening:
a. Clinically significant Vitamin B12 levels < the lower limit of normal (LLN) or on replacement Vitamin B12 for < 3 mos prior to enrollment;
b. Clinically significant folate levels < the LLN or on replacement folate therapy for < 3 mos prior to enrollment;
c. TSH levels > the ULN AND a free thyroxine level lower than the LLN;
d. Positive Rapid Plasma Reagin confirmed by Fluorescent Treponemal Antibody - Absorption;
e. Total bilirubin, ALT or AST > 2 times the ULN;
f. Renal impairment with a serum creatinine > 133 µmol/L (1.5 mg/dL);
g. Hematocrit < 37% for males or < 32% for females, absolute neutrophil cell count of less than or equal to 1,500/ µL, or platelet cell count of < 120,000/µL;
8. Have taken or plan to take a cholinesterase inhibitor other than donepezil within 6 mos prior to Screening through the end of study;
9. Have taken or plan to take memantine within 90 days prior to Screening through the end of study;
10. Have taken or plan to take a prescription medical food or prescription nutriceutical marketed for AD or cognitive impairment within 30 days of Screening through the end of study;
11. Have a history of hypersensitivity to Dimebon or other antihistamines;
12. Have used non-selective antihistamines within 7 days prior to the start of dosing;
13. Have used
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method