| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild to moderate Alzheimer's Disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The objective of this study is to compare the efficacy and safety of two doses of
ABT-126 to placebo in subjects with mild-to-moderate Alzheimer's Disease. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Pharmacogenetic testing in a sub-group of subjects who have provided consent as per section 5.3.1.2 of the protocol. |
|
| E.3 | Principal inclusion criteria |
1. The subject and caregiver must voluntarily sign and date an informed consent,
approved by an Independent Ethics Committee (IEC)/Institutional Review Board
(IRB), prior to the initiation of any study-specific procedures, including
withdrawal of medications to qualify for the study. If the subject is not fully
competent, full informed consent must be obtained from the subject's
representative and assent must be obtained from the subject.
2. The subject is a male or female between the ages of 55 and 90 years of age,
inclusive, at Screening Visit 1.
3. The subject meets the NINCDS/ADRDA criteria for probable AD.
4. The subject has a Mini-Mental Status Examination (MMSE) total score of 10 to
24, inclusive, at Screening Visit 1.
5. The subject has a Cornell Scale for Depression in Dementia (CSDD) score ≤ 10 at
Screening Visit 1.
6. The subject has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4 at
Screening Visit 1.
7. If female, subject must be postmenopausal for at least two years or surgically
sterile (e.g., bilateral tubal ligation or salpingectomy, bilateral oophorectomy or
hysterectomy).
8. If male, the subject is surgically sterile (vasectomy), is sexually inactive, or is
using a barrier method of birth control (e.g., condom) with spermicidal
foam/gel/film/cream/suppository for the duration of the study and for 30 days
following the last dose of study drug. However, if the male subject's partner has
been postmenopausal for at least two years or is surgically sterile, then use of a
barrier method of birth control is not required.
9. The 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 and provide accurate information about the subject's
status during the study.
10. The subject and caregiver are fluent in the language used for administration the
rating scales and cognitive tests and have sufficient visual, hearing and
graphomotor skills to complete procedures.
11. The subject has had a computerized tomography (CT) or magnetic resonance
imaging (MRI) scan, interpreted by a radiologist or neurologist, within 36 months
prior to randomization and after the subject met NINCDS/ADRDA diagnostic
criteria for probable AD. The scan must not show evidence for an alternative
etiology for dementia.
12. With the exception of a diagnosis of mild-to-moderate AD and the presence of
stable medical conditions, the subject is in general good health, based upon the
results of medical history, physical examination, vital signs, laboratory profile, and
a 12-lead ECG |
|
| E.4 | Principal exclusion criteria |
1. The subject is of child-bearing potential or is a pregnant or breast-feeding female.
2. The subject is currently taking or has taken a medication for the treatment of AD or dementia within 60 days prior to Screening Visit 1, or is participating in cognitive therapy for the treatment of AD or dementia. No subject should be discontinued from an efficacious medication solely for the purpose of enrolling in this study.
3. The subject is currently taking or has taken warfarin, acenocoumarol, or phenprocoumon, or another Vitamin K antagonist within 30 days of Screening Visit 1.
4. The subject has a clinically significant abnormal ECG or an ECG with a QTcB
interval of >450 msec for males and >470 msec for females at Screening Visit 1.
5. The subject currently has atrial fibrillation or has a history of sick sinus syndrome
(unless subject has a functioning pacemaker) or any other supraventricular
tachyarrhythmia.
6. The subject has a positive urine drug screen for drugs of abuse. Refer protocol for details.
7. The 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 two years prior to Screening Visit 1.
8. The subject has an abnormally low Vitamin B12 (cobalamin), or an abnormally
high thyroid stimulating hormone (TSH) at the Screening Visit 1 that is considered
clinically significant by the investigator.
9. The subject has a positive Rapid Plasma Reagin (RPR) test at Screening Visit 1.
Refer protocol for details.
10. The subject has a known positive test result for Human Immunodeficiency Virus
(HIV) as per protocol.
11. The subject has a history of any significant neurologic disease other than AD
Refer protocol for details.
12. Within three years of Screening Visit 1, the subject has had clinically significant
symptoms or received treatment for a CNS tumor or subdural hematoma.
13. Within six months of Screening Visit 1, the subject has had a myocardial
infarction, unstable angina, stroke, transient ischemic attack or required
intervention for any of these conditions - refer protocol.
14. Screening Visit 1 laboratory results show the presence of Hepatitis B surface
antigen (HBsAg) or Hepatitis C antibody (HCV Ab) confirmed by a positive
recombinant immunoblot assay (RIBA) test for HCV.
15. The subject has clinically significant abnormal laboratory values at Screening
Visit 1 as determined by the investigator.
16. In the opinion of the investigator, the subject has any clinically significant
uncontrolled medical or psychiatric illness.
17. The subject has reported history of discontinuation of donepezil due to lack of
efficacy after the subject has been compliant with an adequate treatment regimen
(e.g., ≥ 5 mg donepezil for ≥ 3 months).
18. The subject has a history of intolerance or adverse reaction to donepezil that led to discontinuation.
19. The subject has a known hypersensitivity to donepezil, piperidine derivatives, or
any of the excipients in either donepezil hydrochloride or ABT-126 formulations.
20. The subject has experienced unexplained syncope within one year prior to
Screening Visit 1.
21. The subject has had an upper gastrointestinal bleeding episode that required
hospitalization within two years of Screening Visit 1 or has current symptoms of
moderate to severe peptic ulcer disease.
22. The subject has current symptoms of poorly controlled bladder outflow
obstruction.
23. The subject has a history of asthma or obstructive pulmonary disease that requires oxygen supplementation or has resulted in hospitalization in the year prior to Screening Visit 1.
24. The subject has a serum creatinine ≥ 1.7 mg/dL (150.5 mmol/L) if male or ≥ 1.6 mg/dL (141.6 mmol/L) if female at Screening Visit 1.
25. The subject has a history or evidence of a malignancy within the two years prior to Screening Visit 1. Refer protocol for details.
26. The subject has received any investigational product within six weeks prior to
Screening Visit 1. Refer protocol for details.
27. The subject is currently participating or plans to participate in another
interventional study during the course of this trial or has previously participated in
this study, or another study with ABT-126.
28. The subject has received medications with possible psychotropic effects within the 2 weeks prior to Screening Visit 1. Refer protocol for exceptions.
29. The subject cannot swallow or has difficulty swallowing whole capsules.
30. For any reason the investigator considers the subject to be an unsuitable candidate to receive ABT-126 or donepezil.
31. The subject met the NINCDS/ADRDA criteria for probable AD before the age of
50 years.
32. Subjects with high AST, ALT or bilirubin values may not enroll - refer protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy measure will be the Alzheimer's Disease Assessment
Scale - cognitive subscale (ADAS-cog). ADAS-Cog (13-item) will be administered
throughout the study and the primary efficacy variable will be the change from baseline to final evaluation on the ADAS-cog total score (11-item). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end-of-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer. (Refer section 13 of the protocol) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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