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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00940589
Recruitment Status : Completed
First Posted : July 16, 2009
Last Update Posted : July 16, 2013
Information provided by (Responsible Party):
Neurim Pharmaceuticals Ltd.

July 15, 2009
July 16, 2009
July 16, 2013
September 2009
February 2013   (Final data collection date for primary outcome measure)
ADAS-cog [ Time Frame: 24 weeks ]
PSQI question 4 (to be completed by investigator with the spouse or caregiver). [ Time Frame: 12 weeks ]
Complete list of historical versions of study NCT00940589 on Archive Site
IADL, PSQI global score [ Time Frame: 24 weeks ]
Daily Sleep Diary, PSQI, SDI, actigraphy measurements, ADAS cog score, CIBIC Plus, ADL, IADL, WHO-5 and caregiver PSQI. [ Time Frame: 28 weeks ]
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Efficacy of Circadin® 2 mg in Patients With Mild to Moderate Alzheimer Disease Treated With AChE Inhibitor
A Double-blind, Parallel Group, Randomized, Placebo Controlled Study of the Efficacy of Circadin® 2mg in Patients With Mild to Moderate Alzheimer Disease (AD) Treated With Acetylcholinesterase (AChE) Inhibitor
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.
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Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Alzheimer's Disease
  • Sleep Disorder
  • Drug: Circadin
    Prolonged Release melatonin (Circadin) 2mg tablets
  • Drug: Placebo
    Matched placebo tablets, with identical features to the Circadin tablets
  • Experimental: Circadin
    Intervention: Drug: Circadin
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 2013
February 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written informed consent as dictated by local legal circumstances.
  2. Age range: adult patients between 50-85 years of age.
  3. 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.
  4. A documented history of confirmed Alzheimer's disease
  5. Dementia severity: MMSE score > 15,
  6. Stable AChE inhibitor dose for 2 months prior to Screening visit.
  7. Stable medications for non-excluded concurrent medical conditions for four weeks prior to the screening visit.
  8. Stable doses of B12 and/or Folic acid supplements for at least 3 months prior to enrollment and throughout the study.
  9. 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.
  10. 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.
  11. Clinical laboratory values must be within normal limits, or judged not clinically significant by the investigator.
  12. Residence: Stable home situation with no planned move during the 28-week investigational period.
  13. 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.
  14. Ability to ingest oral medication and participate in all scheduled evaluations.
  15. Ability to spend 2 daily hours outdoors exposed to sunlight.

Exclusion Criteria:

  1. Severe agitation.
  2. Unstable medical condition, mental retardation.
  3. moderate to severe depression as defined by DSM-IV
  4. Use of benzodiazepines or other hypnotics during the study and the preceding four weeks.
  5. Use of Circadin® during the two weeks prior to study enrollment.
  6. Pharmacological immunosuppression.
  7. Participation in a clinical trial with any investigational agent within two months prior to study enrollment.
  8. Alcoholism.
  9. Known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists.
  10. Patients with rare hereditary problems of galactose intolerance, the LAPP lactose deficiency or glucose mal absorption.
  11. Renal Failure with creatinine >150 micromol/l.
  12. Hepatic Failure with ASAT; ALAT; GGT levels above three times the upper normal limit.
  13. Clinically significant abnormal laboratory findings which have not been approved by the Safety Officer (sponsor)
  14. Other serious diseases that could interfere with patient assessment.
  15. Caregivers who are unwilling or unable to give informed consent or otherwise fulfill requirements of the study.
  16. Untreated B12 and/or Folic acid deficiency.
Sexes Eligible for Study: All
50 Years to 85 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Israel,   United Kingdom,   United States
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Neurim Pharmaceuticals Ltd.
Neurim Pharmaceuticals Ltd.
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Not Provided
Neurim Pharmaceuticals Ltd.
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP