Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment

Tracking Information
First Submitted Date ICMJE	January 16, 2007
First Posted Date ICMJE	January 17, 2007
Last Update Posted Date	October 24, 2012
Study Start Date ICMJE	January 2007
Actual Primary Completion Date	January 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 10, 2012)	Change from baseline to Week 12 on the Composite Memory Variable [ Time Frame: 12 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: January 16, 2007)	The primary outcome measure is the change from baseline (Day 1) to Week 12 on the Composite Memory Variable
Change History	Complete list of historical versions of study NCT00422981 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 10, 2012)	Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16 [ Time Frame: 16 weeks ]; Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16). [ Time Frame: 16 weeks ]
Original Secondary Outcome Measures ICMJE; (submitted: January 16, 2007)	Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16; Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16).
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment
Official Title ICMJE	A Phase 2, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Effect on Cognitive Function of AL-108 After 12 Weeks of Intranasal Administration in Subjects With Mild Cognitive Impairment
Brief Summary	The purpose of this study is to find out if different doses of Investigational Drug are safe, tolerable, and if they have an effect on Mild Cognitive Impairment (MCI).
Detailed Description	Pre-Clinical experiments indicate the AL-108 compound has neuroprotective, cognitive protective and neurotrophic properties; therefore, the compound could be tested in a variety of human diseases. Human diseases include Cognitive impairment associated with aging or neurodegenerative diseases such as Alzheimer's Disease. This clinical trial aims at providing the dose rationale as well as safety and tolerability information for AL-108 as evaluated after 12 weeks of intranasal administration in subjects with Mild Cognitive Impairment (MCI). There are currently no drugs approved for the treatment of MCI nor accepted treatment or standard treatment approach.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Mild Cognitive Impairment, So Stated
Intervention ICMJE	Drug: AL-108 5 mg QD; Drug: AL-108 15 mg BID; Drug: Placebo Placebo
Study Arms	Active Comparator: AL-108 5 mg 5 mg QD Intervention: Drug: AL-108; Active Comparator: AL-108 15 mg 15 mg BID Intervention: Drug: AL-108; Placebo Comparator: Placebo Placebo Intervention: Drug: Placebo
Publications *	Morimoto BH, Schmechel D, Hirman J, Blackwell A, Keith J, Gold M; AL-108-211 Study. A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Dement Geriatr Cogn Disord. 2013;35(5-6):325-36. doi: 10.1159/000348347. Epub 2013 Apr 13.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 10, 2012)	144
Original Enrollment ICMJE; (submitted: January 16, 2007)	120
Actual Study Completion Date	January 2008
Actual Primary Completion Date	January 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Is male or female, at 55-85 years of age (inclusive) at screening; Self-reported memory complaint, corroborated by spouse or companion as appropriate.; Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5.; Mini-Mental State Exam (MMSE) ≥24.; Center for Epidemiologic Studies-Depression (CES-D) score <27.; Normal thyroid function, defined as TSH, T3 and T4 within normal limits.; Agree not to consume alcoholic beverages within 8 hours of each study visit.; Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol.; Fluently reads and speaks English.; Female subjects must be surgically sterile or post-menopausal for at least 2 years. If <2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained. Exclusion Criteria: Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk. Subjects with a history of uncomplicated depression may participate if in remission and on a stable dose of antidepressant medication for at least 2 months.; History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.; History of alcohol or substance abuse or dependence within the past year.; Acute infective sinusitis.; History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a "broken nose" at least 2 years previously, or surgical repair of cleft palate when <30 years of age.; Use of medications that are known to cause frank obtundation of cognition; Use of any approved or investigational medication for Alzheimer's Disease within 3 months of screening; History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern.; Untreated sleep apnea or treatment for sleep apnea for <3 months.; Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) >2 х the upper limit of normal (ULN),Hematology <80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator.; Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening.; Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period.
Sex/Gender	Sexes Eligible for Study: All
Ages	55 Years to 85 Years (Adult, Older Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00422981
Other Study ID Numbers ICMJE	AL-108-211
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Allon Therapeutics
Study Sponsor ICMJE	Allon Therapeutics
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Donald E Schmechel, MD Memory Assessment and Research Services
PRS Account	Allon Therapeutics
Verification Date	October 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP