Mild to Moderate Dementia of the Alzheimer’s Type (AD) MedDRA version: 14.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: AZD3480 or TC-1734-226
Product Code: AZD3480 or TC-1734-226
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: AZD3480 also known as TC-1734
CAS Number: 691882-47-0
Current Sponsor
Sponsors
Targacept, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A clinical diagnosis of probable dementia of the Alzheimer’s type (Alzheimer’s disease; AD) per National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria at least 12 months prior to Screening, supported by brain imaging studies within the previous 6 months, and of mild to moderate severity as defined by a Mini-Mental State Examination (MMSE) score of 12 to 22. 2. Age 60-85, males or females. 3. Presence of a caregiver with significant proportion of time in contact with the subject and who will oversee administration of study drug during the trial. 4. Able to complete tests assessments and to understand and sign an informed consent (with help of his/her legally authorized representative if needed). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1. Vascular dementia, verified per National Institute of Neurological Disorders and Stroke and Association Internationale pour la Rechererchi et l’Enseignement en Neurosciences (NINDS-AIRENS) criteria and as defined by a modified Hachinski ischemia score (HIS) score of > 4 (i.e., vascular dementia is consistent with a modified HIS > 4). 2. Diagnosis or presence of other dementing illnesses. 3. Use of mood stabilizers, antidepressants, anxiolytics, antipsychotics or hypnotics. 4. Treatment within 1 month prior to Screening using cognition-affecting agents (e.g., CNS stimulants). 5. Tobacco user within 4 months prior to Screening. 6. Use of smoking cessation therapy within 4 months prior to Screening. 7. Use of prohibited concomitant medications (see protocol Section 5.3.2. and Appendix 12). 8. History within past 6 months of alcohol abuse or illicit drug abuse. 9. Unable, even with caregiver assistance, to comply with study procedures in opinion of investigator. 10. History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder: or diagnosis of major depressive disorder. 11. Myocardial infarction within 12 months prior to Screening. 12. Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency. 13. Known systemic infection (HBV, HCV, HIV, TB). 14. Clinically significant finding on baseline physical examination. 15. Clinically significant baseline laboratory or ECG abnormality, including QTcF > 450 msec. 16. The subject is pregnant. 17. Males or WOCBP (FSH >35 IU/L and a LH level >25 IU/L) who are unwilling to comply with contraceptive measures as described in the protocol. 18. Malignancies other than benign skin cancers 19. Participation in another clinical trial in the past 6 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of AZD3480 vs. donepezil as monotherapy in patients with mild to moderate Dementia of the Alzheimer’s Type (AD);Secondary Objective: To assess the safety and tolerability of AZD3480 as monotherapy in patients with mild to moderate AD. To assess the pharmacokinetics of AZD3480 and to investigate pharmacokinetic/pharmacodynamic (PK/PD) relationships in patients with mild to moderate AD.;Primary end point(s): -The change in the Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) total score from Baseline to Week 52. -The change in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) total score from Baseline to Week 52.;Timepoint(s) of evaluation of this end point: Primary endpoints (ADAS-Cog and ADCS-ADL) are assessed at Week -3 (Screening), Day 1 (Baseline and Randomization), Week 4, Week 12, Week 24, Week 36, Week 52 or Early Withdrawal (Final Study Period Visit), and Week 54 (Follow-up Visit). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoints -The change in the Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC-(+)) from Baseline to Week 52. -The change in the Neuropsychiatric Inventory (NPI) total score from Baseline to Week 52. Other Secondary Efficacy Endpoints -The change in the Mini-Mental State Examination (MMSE) total score from Baseline to Week 52. -The proportion of responders (defined as the proportion of subjects with >/= 1 point improvement from Baseline on ADAS-Cog and no deterioration in CIBIC-(+) or ADCS-ADL at Weeks 24 and 52. -The change in ADAS-Cog, CIBIC-(+), ADCS-ADL, and MMSE total scores from Baseline to Weeks 4, 12, 24, 36. -The change in the ADRQL total score from Baseline to Week 24 and 52. -The change in the NPI total score from Baseline to Weeks 12, 24 and 36. -The change in the Resource Utilization in Dementia (RUD) from baseline to week 52. Safety Endpoints -The frequency of clinically significant changes in physical examination findings -The frequency of volunteered non-serious AEs and SAEs -Changes in vital signs (including orthostatic blood pressure and heart rate) -Changes in ECG findings. -Changes in clinical laboratory tests (including hematology, plasma biochemistry, liver function tests (LFTs), and urinalysis). The proportion of values outside of the Targacept (TRGT) reference ranges will be determined. -Urinary cotinine values -Changes in scores on the Columbia Suicide Severity Rating Scale (CSSRS) -Pharmacokinetic exposure parameters for AZD3480 will be estimated based on pre-dose and post-dose values, as appropriate. -Pharmacogenetic endpoints: the key efficacy endpoints will be categorized by Apolipoprotein E (ApoE) allele status. -Pharmacokinetic/Pharmacodynamic analysis will be performed on efficacy endpoints including ADASCog and CIBIC-(+). Other efficacy and safety endpoints may be evaluated, as appropriate.;Timepoint(s) of evaluation of this end poin | — |
Countries
Czech Republic, Romania, Slovakia, Ukraine, United States
Contacts
Public ContactRegulatory Affairs
Chiltern International
Outcome results
None listed