Efficacy of Circadin® 2 mg in Patients With Mild to Moderate Alzheimer Disease Treated With AChE Inhibitor

NCT00940589 | Completed Phase 2 Results

• 1 other identifier: NEU AZ1
• Study Type: interventional
• Target: 73
• Locations: 3 countries
• Sites: 6

Brief Summary

The aim of this exploratory randomized, placebo controlled study is to evaluate the efficacy of Circadin® 2mg in patients with mild to moderate Alzheimer Disease (AD) treated with the acetylcholinesterase (AChE) inhibitor. The effects of add-on Circadin® 2mg vs. placebo on the decline in cognitive skills and global functioning, as well as on daytime somnolence and will be assessed.

Conditions

Alzheimer's Disease; Sleep Disorder

Keywords

Alzheimer's Disease; Acetylcholinesterase inhibitor; cognitive function; Circadin; Sleep disturbances

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to 24 Weeks in ADAS-cog

  ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a cognitive testing instrument used in clinical trials. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD. The test comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline. ADAS-cog was measured at base line and at end of treatment after 24 weeks.

  24 weeks

Secondary Outcomes (2)

• Change From Baseline to 24 Weeks in iADL

  24 weeks

• Change From Baseline to 24 Weeks in MMSE

  24 weeks

Study Arms (2)

Circadin

EXPERIMENTAL

Drug

Drug: Circadin

Placebo

PLACEBO COMPARATOR

drug

Drug: Placebo

Interventions

Circadin DRUG

Prolonged Release melatonin (Circadin) 2mg tablets

Circadin

Placebo DRUG

Matched placebo tablets, with identical features to the Circadin tablets

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent as dictated by local legal circumstances.
• Age range: adult patients between 50-85 years of age.
• Gender: men and women. Women of child bearing potential or within two years of the menopause must have a negative urine pregnancy test at the Screening Visit.
• A documented history of confirmed Alzheimer's disease
• Dementia severity: MMSE score \> 15,
• Stable AChE inhibitor dose for 2 months prior to Screening visit.
• Stable medications for non-excluded concurrent medical conditions for four weeks prior to the screening visit.
• Stable doses of B12 and/or Folic acid supplements for at least 3 months prior to enrollment and throughout the study.
• Cranial image: no evidence of focal disease to account for dementia (established by CT, PET or MRI). If there is no such available scan (CT, PET or MRI), one must be performed prior to enrollment.
• Health: Physically acceptable for the study with no pathology likely to occur during or immediately after the study, as confirmed by medical history and exam and ECG.
• Clinical laboratory values must be within normal limits, or judged not clinically significant by the investigator.
• Residence: Stable home situation with no planned move during the 28-week investigational period.
• A family member or a regular caregiver that will be available for visits and will ensure compliance. The caregiver must speak fluent Hebrew, Russian or English.
• Ability to ingest oral medication and participate in all scheduled evaluations.
• Ability to spend 2 daily hours outdoors exposed to sunlight.

You may not qualify if:

• Severe agitation.
• Unstable medical condition, mental retardation.
• moderate to severe depression as defined by DSM-IV
• Use of benzodiazepines or other hypnotics during the study and the preceding four weeks.
• Use of Circadin® during the two weeks prior to study enrollment.
• Pharmacological immunosuppression.
• Participation in a clinical trial with any investigational agent within two months prior to study enrollment.
• Alcoholism.
• Known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists.
• Patients with rare hereditary problems of galactose intolerance, the LAPP lactose deficiency or glucose mal absorption.
• Renal Failure with creatinine \>150 micromol/l.
• Hepatic Failure with ASAT; ALAT; GGT levels above three times the upper normal limit.
• Clinically significant abnormal laboratory findings which have not been approved by the Safety Officer (sponsor)
• Other serious diseases that could interfere with patient assessment.
• Caregivers who are unwilling or unable to give informed consent or otherwise fulfill requirements of the study.

Sponsors & Collaborators

• Neurim Pharmaceuticals Ltd.: lead

Study Sites (6)

Meridien Research

Brooksville, Florida, 34601, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

Exodon LLC

Mount Arlington, New Jersey, 07856, United States

Location

Scranton Medical Institute

Scranton, Pennsylvania, 18503, United States

Location

Merchav clinics

Tel Aviv, Israel

Location

CPS Research

Glasgow, G20 0XA, United Kingdom

Location

Related Publications (2)

• Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. eCollection 2014.

  PMID: 24971004 RESULT

• McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.

  PMID: 33189083 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Sleep Wake Disorders; Parasomnias

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Amnon Katz
• Organization: Neurim Pharmaceuticals (1991) LTD

amnonk@neurim.com

972-3-768-4906

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2009
• First Posted: July 16, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 1, 2018
• Results First Posted: June 1, 2018

Record last verified: 2018-05

Locations

US (4); IL (1); GB (1)