Trial Outcomes & Findings for Efficacy of Circadin® 2 mg in Patients With Mild to Moderate Alzheimer Disease Treated With AChE Inhibitor (NCT NCT00940589)

Last Updated: 2018-06-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

24 weeks

Results posted on

2018-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Circadin Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets	Placebo drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets
Overall Study STARTED	39	34
Overall Study COMPLETED	31	29
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Circadin n=39 Participants Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets	Placebo n=34 Participants drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets	Total n=73 Participants Total of all reporting groups
Age, Continuous	73.5 years STANDARD_DEVIATION 8.6 • n=93 Participants	77.3 years STANDARD_DEVIATION 6.6 • n=4 Participants	75.4 years STANDARD_DEVIATION 7.6 • n=27 Participants
Sex: Female, Male Female	16 Participants n=93 Participants	20 Participants n=4 Participants	36 Participants n=27 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	14 Participants n=4 Participants	37 Participants n=27 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets	Circadin n=29 Participants Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets
Change From Baseline to 24 Weeks in ADAS-cog	0.19 Scores on a scale Standard Deviation 6.28	0.45 Scores on a scale Standard Deviation 5

SECONDARY outcome

Timeframe: 24 weeks

Instrumental Activities of Daily Living (iADL). The scale rates activities that represent key life tasks that people need to manage. These tasks are valuable for evaluating persons with early-stage disease, both to assess the level of disease and to determine the person's ability to care for himself or herself. Scores of 0 or 1 are given to every task (Bathing, Dressing, Tolieting, transferring, Continence and Feeding) to a total score of 6. , while 0 represents a patient who is very dependent and 6 represents patient who is independent. iADL was measured at base line and at end of treatment after 24 weeks.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets	Circadin n=31 Participants Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets
Change From Baseline to 24 Weeks in iADL	1.62 Scores on a scale Standard Deviation 1.57	0.77 Scores on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: 24 weeks

The Mini Mental State Examination (MMSE) is a brief assessment instrument used to assess cognitive function in elderly patients. The MMSE can be used to screen for cognitive impairment and as a measurement of cognition over time and with pharmacologic treatment. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention: the maximum score is 21. The second section tests the ability of the patient to name objects, follow verbal and written commands, write a sentence, and copy figures: the maximum score is 9. The scoring range for the MMSE is 0-30. Higher score represents better performance. MMSE was measured at base line and at end of treatment after 24 weeks.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets	Circadin n=32 Participants Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets
Change From Baseline to 24 Weeks in MMSE	-1.9 Scores on a scale Standard Deviation 3.5	-0.3 Scores on a scale Standard Deviation 2.8

Adverse Events

Circadin

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Circadin n=39 participants at risk Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets	Placebo n=34 participants at risk drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets
Metabolism and nutrition disorders Dehydration	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Renal and urinary disorders Urinary tract infection	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Respiratory, thoracic and mediastinal disorders esophageal stenosis	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Cardiac disorders Severe miocardial infraction	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
General disorders Fatigue	2.6% 1/39 • Number of events 1 • 26 weeks	0.00% 0/34 • 26 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 1/39 • Number of events 1 • 26 weeks	0.00% 0/34 • 26 weeks
Nervous system disorders Somnolence	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Gastrointestinal disorders Gastritis	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Endocrine disorders Hyperglycaemia	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/39 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks

Other adverse events

Other adverse events
Measure	Circadin n=39 participants at risk Drug Circadin: Prolonged Release melatonin (Circadin) 2mg tablets	Placebo n=34 participants at risk drug Placebo: Matched placebo tablets, with identical features to the Circadin tablets
Cardiac disorders Angina pectoris	7.7% 3/39 • Number of events 3 • 26 weeks	0.00% 0/34 • 26 weeks
Gastrointestinal disorders Abdominal discomfort	10.3% 4/39 • Number of events 4 • 26 weeks	0.00% 0/34 • 26 weeks
Gastrointestinal disorders Diarrhoea	10.3% 4/39 • Number of events 4 • 26 weeks	5.9% 2/34 • Number of events 2 • 26 weeks
Gastrointestinal disorders Nausea	0.00% 0/39 • 26 weeks	5.9% 2/34 • Number of events 2 • 26 weeks
Gastrointestinal disorders Vomiting	7.7% 3/39 • Number of events 3 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
General disorders Fatigue	5.1% 2/39 • Number of events 2 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Injury, poisoning and procedural complications Fall	7.7% 3/39 • Number of events 3 • 26 weeks	0.00% 0/34 • 26 weeks
Blood and lymphatic system disorders Blood creatinine increased	0.00% 0/39 • 26 weeks	5.9% 2/34 • Number of events 2 • 26 weeks
Blood and lymphatic system disorders Blood glucose increased	5.1% 2/39 • Number of events 2 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Metabolism and nutrition disorders Decreased appetite	5.1% 2/39 • Number of events 2 • 26 weeks	0.00% 0/34 • 26 weeks
Musculoskeletal and connective tissue disorders Back pain	5.1% 2/39 • Number of events 2 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Nervous system disorders Abnormal dreams	5.1% 2/39 • Number of events 2 • 26 weeks	0.00% 0/34 • 26 weeks
Psychiatric disorders Agitation	5.1% 2/39 • Number of events 2 • 26 weeks	5.9% 2/34 • Number of events 2 • 26 weeks
Psychiatric disorders Cognitive disorder	2.6% 1/39 • Number of events 1 • 26 weeks	5.9% 2/34 • Number of events 2 • 26 weeks
Psychiatric disorders Insomnia	5.1% 2/39 • Number of events 2 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Renal and urinary disorders Urinary tract infection	2.6% 1/39 • Number of events 1 • 26 weeks	14.7% 5/34 • Number of events 6 • 26 weeks
Respiratory, thoracic and mediastinal disorders Cough	5.1% 2/39 • Number of events 2 • 26 weeks	0.00% 0/34 • 26 weeks
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	5.1% 2/39 • Number of events 2 • 26 weeks	2.9% 1/34 • Number of events 1 • 26 weeks
Respiratory, thoracic and mediastinal disorders Sinusitis	5.1% 2/39 • Number of events 2 • 26 weeks	0.00% 0/34 • 26 weeks
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	5.1% 2/39 • Number of events 2 • 26 weeks	8.8% 3/34 • Number of events 3 • 26 weeks

Additional Information

Amnon Katz

Neurim Pharmaceuticals (1991) LTD

Phone: 972-3-768-4906

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60