Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Targacept Inc.
ClinicalTrials.gov Identifier:
NCT01466088
First received: November 2, 2011
Last updated: July 15, 2014
Last verified: July 2014

November 2, 2011
July 15, 2014
October 2011
May 2014   (final data collection date for primary outcome measure)
  • Change from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the Clinician Interview-Based Impression of Change plus carer interview [CIBIC-(+)] [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    The CIBIC-(+) is a co-primary endpoint with the ADAS-Cog in the United States.
  • Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    The ADCS-ADL is the co-primary endpoint with the ADAS-Cog in Europe.
  • CIBIC-(+) [ Time Frame: 54 Weeks ] [ Designated as safety issue: No ]
    The Clinician Interview-Based Impression of Change carer interview (CIBIC-Plus) comprises Likert scales for disease severity and changes, and written accounts summarizing semistructured interviews evaluating behavior, cognition, and function. It will be collected at Week -3, Day 1, Weeks 4, 12, 24, 36, 52, and 54 or early withdrawal and will be a co-primary outcome for the US and a secondary outcome measure for Europe.
  • ADCS-ADL [ Time Frame: 54 Weeks ] [ Designated as safety issue: No ]
    Alzheimer's Disease Cooperative Study - Activities of Daily Living is a caregiver rated questionnaire of 23 items, with possible scores over a range of 0-78, where 78 implies full functioning with no impairment. It will be the co-primary outcome measure in Europe and a secondary outcome measure in the US. ADCS-ADL will be collected at Week -3, Day 1, Weeks 4, 12, 24, 36, 52, and 54 or early withdrawal.
  • ADAS-Cog [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    The ADAS-Cog tests patients' abilities in memory, language, orientation, and praxis, where higher scores (sum of errors) indicate declining cognition. ADAS-Cog will be collected at Week -3, Day 1, Weeks 4, 12, 24, 36, 52, and 54 or early withdrawal.
Complete list of historical versions of study NCT01466088 on ClinicalTrials.gov Archive Site
  • Change from baseline in the Neuropsychiatric Inventory (NPI) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the Mini-Mental State Examination (MMSE) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the Alzheimer's Disease Related Quality of Life (ADRQL) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
NPI [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
Neuropsychiatric Inventory (NPI) at Day 1, Week 12, Week 24, and Week 52 or EW.
Not Provided
Not Provided
 
Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)
Double-Blind, Positive Comparator, Randomized, Parallel Study of Efficacy, Safety, and Tolerability of AZD3480 (TC-1734-226) as Monotherapy in Patients With Mild to Moderate Dementia of the Alzheimer's Type

Alzheimer's disease is the most common form of dementia and is the fourth leading cause of death among people 65 years of age and older. The global prevalence of the disease will increase significantly as the population ages, unless preventative treatments can be identified and marketed. The present study seeks to evaluate AZD3480 (TC-1734) compared to an approved medication (donepezil) shown to improve cognition and function in patients with Alzheimer's disease.

This is a double blind, positive comparator, randomized, multicenter, parallel group study to assess the efficacy, safety, and tolerability of AZD3480 as monotherapy in patients with mild to moderate dementia of the Alzheimer's type (AD). Approximately 300 subjects will be randomized and divided into 2 cohorts. Actual randomization was 293 subjects.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: Donepezil
    Subjects taking donepezil will take 1-2 capsules of 5 mg donepezil and a placebo for AZD3480 (to maintain blind) orally once a day.
    Other Name: Aricept
  • Drug: AZD3480
    Subjects taking 30 mg AZD3480 will take one capsule of AZD3480 and two capsules of placebo for donepezil (to maintain blind) orally once a day.
    Other Name: TC-1734
  • Experimental: AZD3480
    Intervention: Drug: AZD3480
  • Active Comparator: Donepezil
    Donepezil will be administered at 5 mg daily for 4 weeks and escalated to 10 mg daily for the remainder of the study.
    Intervention: Drug: Donepezil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
386
May 2014
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. A clinical diagnosis of AD per NINCDS-ADRDA criteria; mild to moderate severity as defined by Mini-Mental State Examination (MMSE) scores of 12 to 22.
  2. AD diagnosed at least 12 months prior to Screening, and supported by brain imaging studies within 6 months prior to Screening.
  3. Absence of vascular dementia both per AIRENS criteria and as defined by modified Hachinski ischemia score (HIS) of </= 4.
  4. Presence of a caregiver with significant proportion of time in contact with subject and who will oversee administration of study drug during the trial
  5. Able to complete test assessments and to sign informed consent with the help of a caregiver if needed

Exclusion Criteria:

  1. Diagnosis or presence of other dementing illnesses
  2. Use of mood stabilizers, antidepressants, anxiolytics, antipsychotics or hypnotics
  3. Treatment within 1 month prior to Screening using cognition-affecting agents (e.g. CNS stimulants)
  4. Tobacco user within 4 months prior to Screening
  5. Use of smoking cessation therapy within 4 months prior to Screening
  6. History within past 6 months of alcohol abuse or illicit drug abuse
  7. Unable, even with caregiver assistance, to comply with study procedures in opinion of investigator
  8. Myocardial infarction within the 12 months prior to Screening
  9. Hypothyroidism, vitamin B12 or folic acid deficiency
  10. Known systemic infection (HBV, HCV, HIV, TB)
  11. Vascular dementia per NINDS-AIRENS criteria and as defined by a modified Hachinski ischemia score (HIS, Appendix 4) score of > 4 (i.e., vascular dementia is consistent with a modified HIS > 4).
Both
60 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Czech Republic,   Romania,   Slovakia,   Ukraine
 
NCT01466088
TC-1734-226-CRD-006
No
Targacept Inc.
Targacept Inc.
Not Provided
Principal Investigator: Pierre Tariot, MD Banner Alzheimer Institute
Targacept Inc.
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP