Clinical trial NCT01137526: Efficacy and Safety Study of ABT-384 in Subjects With Mild-to-Moderate Alzheimer's Disease
Official title: A Randomized, Double-Blind, Placebo and Active-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of ABT-384 in Subjects With Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 267
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test if the investigational medication, ABT-384, is a safe and effective treatment for adults with mild-to-moderate Alzheimer's Disease.

Detailed description: This is a Phase 2 study designed to evaluate the safety and efficacy of ABT-384 in approximately 260 adults with mild-to-moderate Alzheimer's Disease (AD). Subjects will be randomized to one of four treatment groups (ABT-384, donepezil, or placebo) for a 12-week Treatment Period.

Eligibility criteria: Inclusion Criteria:

1. The subject and caregiver must voluntarily sign and date and informed consent. If the subject is not fully competent, full informed consent must be obtained from a legal representative and assent must be obtained from the subject.
2. Subject is male or female between the ages of 55 and 90 years of age, inclusive, at Day-1.
3. Subject meets the NINCDS/ADRDA criteria for probable AD.
4. Subject has a Mini-Mental Status Examination (MMSE) score of 10 to 24, inclusive, at Screening Visit 1.
5. Subject has a Cornell Scale for Depression in Dementia (CSDD) score ≤ 10 at Screening Visit 1.
6. With the exception of a diagnosis of mild-to-moderate AD and the presence of stable medical conditions, the subject is generally in good health based on medical history, physical examination, vital signs, clinical lab tests and 12-lead ECG.
7. If female, subject must be postmenopausal for at least 2 years or surgically sterile.
8. If male, the subject is surgically sterile (vasectomy), is sexually inactive, or is using a barrier method of birth control.
9. Subject has an identified reliable, caregiver (e.g., family member, social worker, nurse), who will provide support and ensure compliance with the study medication and procedures.
10. Subject and caregiver are fluent in the language used for administration of the rating scales or cognitive tests and have sufficient visual, hearing and graphomotor skills to complete procedures.

Exclusion Criteria:

1. Subject has a known hypersensitivity or intolerance to donepezil that led to discontinuation or a known reported history of donepezil treatment failure.
2. Subject is currently taking or has taken a medication for the treatment of AD or dementia within 60 days of Screening Visit 1, or is participating in cognitive therapy for the treatment of AD or dementia.
3. Subject has a history of a drug or alcohol disorder (abuse/dependence), based on either DSM-IV-TR or ICD-10 criteria, excluding nicotine, within 2 years prior to Screening Visit 1.
4. In the opinion of the investigator, the subject has any clinically significant uncontrolled medical or psychiatric illness that would affect the safety of the subject.
5. The subject has a current thyroid disease or history of thyroid disease, and is not currently being treated with a stable dose of thyroid replacement medication.
6. For any reason the investigator considers the subject to be an unsuitable candidate to receive ABT-384 or donepezil.

Primary outcomes:
measure: Change from baseline to final observation in the Alzheimer's Disease Assessment Scale-Cognition portion (ADAS-cog) total score
timeFrame: 12 Weeks
Secondary outcomes:
measure: Mini Mental Status Examination (MMSE) score at Baseline, Weeks 4, 8, and 12
timeFrame: 12 Weeks
measure: Clinician's Interview Based Impression of Change-plus (CIBIC-plus) score at Baseline, Weeks 4, 8, and 12
timeFrame: 12 Weeks
measure: Neuropsychiatric Inventory (NPI) score at Baseline, Weeks 4, 8, and 12
timeFrame: 12 Weeks
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score at Baseline, Weeks 4, 8, and 12
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Ekaterinburg
country: Russian Federation
facility: Site Reference ID/Investigator# 40834
city: Kazan
country: Russian Federation
facility: Site Reference ID/Investigator# 36304
city: Kirov
country: Russian Federation
facility: Site Reference ID/Investigator# 36306
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 37944
city: Saratov
country: Russian Federation
facility: Site Reference ID/Investigator# 26909
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 26904
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 26902
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 36305
city: Yaroslavl
country: Russian Federation
facility: Site Reference ID/Investigator# 38383
city: Belville
country: South Africa
facility: Site Reference ID/Investigator# 45584
city: George
country: South Africa
facility: Site Reference ID/Investigator# 47102
city: Johannesburg
country: South Africa
facility: Site Reference ID/Investigator# 45583
city: Donetsk
country: Ukraine
facility: Site Reference ID/Investigator# 39855
city: Kharkiv
country: Ukraine
facility: Site Reference ID/Investigator# 26914
city: Kiev
country: Ukraine
facility: Site Reference ID/Investigator# 26912
city: Lviv
country: Ukraine
facility: Site Reference ID/Investigator# 40484
city: Poltava
country: Ukraine
facility: Site Reference ID/Investigator# 27002
city: Poltava
country: Ukraine
facility: Site Reference ID/Investigator# 39856
city: Simferopil
country: Ukraine
facility: Site Reference ID/Investigator# 40482
city: Ternopil
country: Ukraine
facility: Site Reference ID/Investigator# 40483
city: Vinnytsia
country: Ukraine
facility: Site Reference ID/Investigator# 35660
city: Bath
country: United Kingdom
facility: Site Reference ID/Investigator# 36327
city: Blackburn
country: United Kingdom
facility: Site Reference ID/Investigator# 35657
city: Crowborough
country: United Kingdom
facility: Site Reference ID/Investigator# 36330
city: Glasgow
country: United Kingdom
facility: Site Reference ID/Investigator# 36326
city: Ivybridge, Devon
country: United Kingdom
facility: Site Reference ID/Investigator# 44123
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 35658
city: Northampton
country: United Kingdom
facility: Site Reference ID/Investigator# 35902
city: Oxford
country: United Kingdom
facility: Site Reference ID/Investigator# 36328
city: Peterborough
country: United Kingdom
facility: Site Reference ID/Investigator# 36329
Study officials:
affiliation: AbbVie
name: Gerard Marek, MD
role: STUDY_DIRECTOR
References:
citation: Marek GJ, Katz DA, Meier A, Greco N 4th, Zhang W, Liu W, Lenz RA. Efficacy and safety evaluation of HSD-1 inhibitor ABT-384 in Alzheimer's disease. Alzheimers Dement. 2014 Oct;10(5 Suppl):S364-73. doi: 10.1016/j.jalz.2013.09.010. Epub 2014 Jan 10.