Trial Outcomes & Findings for Efficacy and Safety of Circadin® 2 mg in the Treatment of Primary Insomnia Patients (NCT NCT00397189)
NCT ID: NCT00397189
Last Updated: 2018-05-01
Results Overview
Sleep latency (SL) after 3 weeks of treatment was assessed by Patient Daily Sleep Diary (National sleep foundation sleep diary). The patients reported subjectively of their SL. The Sleep Diary question 3 (SL) was summarised at baseline (end of the two-week run-in period) and after three weeks double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. At each visit, the mean of the seven days prior to the visit were used. For each treatment group, the mean score at visit 3 was compared, adjusting for the visit 2 score. An ANCOVA model was used. Lower score indicates reduction in sleep latency and thus considered improvement
COMPLETED
PHASE3
930 participants
Baseline and 3 weeks
2018-05-01
Participant Flow
The first patient entered the study on 24 October 2006 and the last patient completed the study (safety follow up) on 2 December 2008 (last patient completed the last visit on 24 October 2008).
930 patients were enrolled into the study and entered the run-in period; 139 of these patients were discontinued during the run-in period. The main reasons for discontinuation from the run-in were unwillingness to continue and ineligible to continue. Treatment periods were 3 weeks double-blind (DB) (1:1) and extension period 26 weeks DB (3:1)
Participant milestones
| Measure |
Circadin
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
3 Weeks Period
STARTED
|
394
|
395
|
|
3 Weeks Period
COMPLETED
|
373
|
373
|
|
3 Weeks Period
NOT COMPLETED
|
21
|
22
|
|
Extension Period
STARTED
|
534
|
177
|
|
Extension Period
COMPLETED
|
421
|
134
|
|
Extension Period
NOT COMPLETED
|
113
|
43
|
Reasons for withdrawal
| Measure |
Circadin
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
3 Weeks Period
Lost to Follow-up
|
5
|
4
|
|
3 Weeks Period
Adverse Event
|
3
|
2
|
|
3 Weeks Period
Withdrawal by Subject
|
13
|
9
|
|
3 Weeks Period
Physician Decision
|
0
|
2
|
|
3 Weeks Period
Protocol Violation
|
0
|
3
|
|
3 Weeks Period
Other
|
0
|
2
|
Baseline Characteristics
Efficacy and Safety of Circadin® 2 mg in the Treatment of Primary Insomnia Patients
Baseline characteristics by cohort
| Measure |
Circadin
n=360 Participants
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
n=362 Participants
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
Total
n=722 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
223 Participants
n=5 Participants
|
218 Participants
n=7 Participants
|
441 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
137 Participants
n=5 Participants
|
144 Participants
n=7 Participants
|
281 Participants
n=5 Participants
|
|
Age, Continuous
|
61.9 years
STANDARD_DEVIATION 10 • n=5 Participants
|
61.5 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
61.7 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
253 Participants
n=5 Participants
|
244 Participants
n=7 Participants
|
497 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
107 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
225 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
360 participants
n=5 Participants
|
362 participants
n=7 Participants
|
722 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 3 weeksPopulation: Pre-planned analysis on ITT population age 65-80
Sleep latency (SL) after 3 weeks of treatment was assessed by Patient Daily Sleep Diary (National sleep foundation sleep diary). The patients reported subjectively of their SL. The Sleep Diary question 3 (SL) was summarised at baseline (end of the two-week run-in period) and after three weeks double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. At each visit, the mean of the seven days prior to the visit were used. For each treatment group, the mean score at visit 3 was compared, adjusting for the visit 2 score. An ANCOVA model was used. Lower score indicates reduction in sleep latency and thus considered improvement
Outcome measures
| Measure |
Circadin
n=137 Participants
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
n=144 Participants
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
The Change From Baseline in Subjective Sleep Latency.
|
-19.1 minutes
Standard Deviation 47.3
|
-1.7 minutes
Standard Deviation 47.8
|
SECONDARY outcome
Timeframe: 3 weeksSleep maintenance as measured by number of awakening (NOA) after 3 weeks of treatment was assessed by Patient Daily Sleep Diary (National sleep foundation sleep diary). The patients reported subjectively of their NOA. The Sleep Diary question 4 (NOA) was summarized at baseline (end of the two-week run-in period) and after three weeks double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. At each visit, the mean of the seven days prior to the visit were used. For each treatment group, the mean score at visit 3 was compared, adjusting for the visit 2 score. An ANCOVA model was used. Lower score indicates less awakenings and thus considered improvement.
Outcome measures
| Measure |
Circadin
n=137 Participants
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
n=144 Participants
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
The Change From Baseline in Subjective Sleep Maintenance.
|
-0.24 Awakenings
Interval -0.33 to 0.0
|
-0.09 Awakenings
Interval -0.33 to 0.0
|
Adverse Events
Circadin
Placebo
Serious adverse events
| Measure |
Circadin
n=394 participants at risk
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
n=395 participants at risk
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
Infections and infestations
cellulitis
|
0.25%
1/394 • Number of events 1 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
0.00%
0/395 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
|
General disorders
chest pain
|
0.00%
0/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
0.25%
1/395 • Number of events 1 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
|
Infections and infestations
upper respiratory tract infection
|
0.00%
0/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
0.25%
1/395 • Number of events 1 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
uterine cancer
|
0.00%
0/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
0.25%
1/395 • Number of events 1 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
Other adverse events
| Measure |
Circadin
n=394 participants at risk
Prolonged release melatonin 2 mg. Tablets should be taken 1-2 hours before going to bed.
|
Placebo
n=395 participants at risk
Identical tablets to Circadin. Tablets should be taken 1-2 hours before going to bed.
|
|---|---|---|
|
Infections and infestations
nasopharyngitis
|
3.3%
13/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
4.1%
16/395 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
|
Infections and infestations
upper respiratory tract infection
|
2.0%
8/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
2.0%
8/395 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
|
Nervous system disorders
headache
|
2.8%
11/394 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
4.6%
18/395 • 37 weeks (2 weeks baseline, 3 weeks double-blind, 26 weeks double-blind extension period and 2 weeks run-out,AEs were to be reported for up to 30 days after stopping study medication )
The safety variables were assessed at each visit and included spontaneously reported adverse events (AEs); unusual events and AEs recorded by the investigator
|
Additional Information
VP clinical and regulatory affairs
Neurim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60