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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466088
• Other study ID #: TC-1734-226-CRD-006
• Status: Completed
• Phase: Phase 2
• First received: November 2, 2011
• Last updated: May 11, 2015
• Start date: October 2011
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlRomania: National Medicines AgencySlovakia: State Institute for Drug ControlUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 386
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 85 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Czech Republic	Policlinic	Chocen
Czech Republic	BRAIN-SOULTHERAPY s.r.o.	Kladno
Czech Republic	Bialbi.s.r.o. Psychiatrické oddelení	Litomerice
Czech Republic	Psychiatricka Ambulance	Olomouc
Czech Republic	Vojenska Nemocnice Psychiatricke oddeleni	Olomouc
Czech Republic	Clintrial	Praha
Czech Republic	PRAGTIS s.r.o.	Praha
Czech Republic	Psychosocialni centrum	Prerov
Romania	Crucea Alba - Dr. Oros si Asociatii - Societate Civila Medicala	Oradea
Romania	Spitalul Clinic Judetean de Urgenta SIBIU	Sibiu
Romania	Spitalul de Psihiatrie Sibiu	Sibiu
Romania	Spitalul Clinic Judetean de Urgenta, Clinica Neurologie 2	Timisoara
Romania	Spitalul Clinic Judetean de Urgenta, Clinica Psihiatrie	Timisoara
Slovakia	Neurologicka Ambulancia, s.r.o.	Banska Bystrica
Slovakia	Univerzitna nemocnica Bratislava, Geronto-psychiatrické oddelenie	Bratislava
Slovakia	KONZILIUM s.r.o.	Dubnica nad Váhom
Slovakia	Neurologická ambulancia	Krompachy
Ukraine	Dnipropetrovsk Regional Clinical Hospital	Dnipropetrovsk
Ukraine	Donetsk National Medical University of M. Gorky	Donetsk
Ukraine	Donetsk Regional Clinical Psychiatric Hospital	Donetsk
Ukraine	Crimean Republican Institution Psychoneurological Dispensary	Kerch
Ukraine	Central Clinical Hospital Ukrzaliznytsi	Kharkiv
Ukraine	Department of Age Physiology and Pathology of Nervous System; Institute of Gerontology NAMS	Kyiv
Ukraine	Lugansk Regional Clinical Psychoneurological Hospital	Lugansk
Ukraine	Lviv National Medical University named after Galytskyy	Lviv
Ukraine	Lviv Regional Clinical Psychiatric Hospital	Lviv
Ukraine	Odessa Regional Psychoneurology Dispensary	Odessa
Ukraine	Odessa Regional Psychiatric Hospital # 2	Oleksandrivka
Ukraine	Ukrainian Medical Stomatological Academy	Poltava
Ukraine	Department #3 of the Kherson Regional Psychiatric Hospital	Stepanovka
United States	Meridien Research	Brooksville	Florida
United States	MD Clinical	Hallandale Beach	Florida
United States	Banner Alzheimer Institute	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Countries where clinical trial is conducted

United States,  Czech Republic,  Romania,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog)		52 weeks	No
Primary	Change from baseline in the Clinician Interview-Based Impression of Change plus carer interview [CIBIC-(+)]	The CIBIC-(+) is a co-primary endpoint with the ADAS-Cog in the United States.	52 Weeks	No
Primary	Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	The ADCS-ADL is the co-primary endpoint with the ADAS-Cog in Europe.	52 Weeks	No
Secondary	Change from baseline in the Neuropsychiatric Inventory (NPI)		52 Weeks	No
Secondary	Change from baseline in the Mini-Mental State Examination (MMSE)		52 Weeks	No
Secondary	Change from baseline in the Alzheimer's Disease Related Quality of Life (ADRQL)		52 Weeks	No