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Health Condition(s) or Problem
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Insomnia
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Lay Summary
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Not provided at time of registration (from ISRCTN)
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Who can enter the trial
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1. Male or female subjects aged 65 years or more presenting with self-reported poor sleep quality defined as at least two of the following:
1.1. Regularly took more than 45 minutes to fall asleep (at least three nights per week)
1.2. Overall night-time sleep less than 5 hours on at least 3 nights per week
1.3. Regular night-time awakenings defined as at least twice per night on at least 3 nights per week
2. Subjects with a poor sleep quality for at least 8 weeks
3. Written informed consent
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Who cannot enter the trial
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1. Had a clinically significant unstable medical abnormality, chronic disease or history or presence of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, psychiatric, metabolic disease or malignancy which in the opinion of the investigator would have precluded successful participation in the study
2. Had a recent history of (less than 2 years) alcohol or drug abuse or current evidence of substance dependence or abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV criteria
3. Had major depression or anxiety causing sleep disturbance as defined by Diagnostic and Statistical Manual of Mental Disorders-IV criteria
4. Had a clinically significant illness within the last 30 days
5. Routine biochemistry parameters (e.g., creatinine or liver function tests) greater than 2 x the upper limit of normal for this age of population. Haemoglobin less than 10 g/dL.
6. Subjects receiving B6 or B12 supplements (multivitamin supplements were allowable provided intake did not exceed the recommended daily dose)
7. Subjects receiving warfarin or other vitamin K antagonists
8. Subjects planning to travel through more than two time zones whilst entered into the study
9. Subjects with a known hypersensitivity to melatonin or any of the excipients in the formulation
10. Subjects who, by virtue of the need to care for a close family member, were subjected to intermittent night-time disturbance
11. Subjects who had experienced the bereavement of a close family member within the last 3 months
12. Subjects who had used any other investigational drug within the last 30 days
13. Subjects planning to work night shifts
14. Subjects on treatment with anxiolytics, antidepressants, anticonvulsants, hypnotics or strong narcotic analgesics within the last 30 days. Other narcotic analgesics were allowed if they had been used at a constant dose for at least the last 30 days, the dose was unlikely to change during the duration of the study and in the opinion of the investigator, not likely to interfere with the subject's sleep quality. Subjects receiving hypnotics were eligible for the study if they consented to withdraw from treatment for 16 days prior to screening.
15. Subjects with a known severe allergic or auto-immune disease
16. Subjects with other conditions that may have caused night-time awakenings (e.g., nocturia or uncontrolled nocturnal pain) that in the investigator's opinion would have interfered with the assessment of the subject's sleep disturbance
17. Subjects who, in the opinion of the investigator, were unlikely to complete the study satisfactorily
Subjects were advised that caution was to be exercised when driving or operating any heavy or dangerous machinery within 6 hours of taking a dose of study medication.
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What will happen
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This was a double-blind, placebo-controlled, randomised, cross-over study of a sustained release formulation of melatonin, APL510, at doses of APL510 1.5 mg and APL510 3.0 mg. It was planned that a total of 26 matched pairs were required for the efficacy analysis. Therefore, in order to reach this number of completed subjects, a total of up to 80 could be recruited, to allow for dropouts.
Subjects had a 2-week treatment-free period run-in to assess their suitability for inclusion. All subjects were then randomised to receive the following active and placebo treatments for a period of 4 weeks, each separated by a 1-week treatment-free period:
1. APL510 1.5 mg followed by placebo followed by APL510 3.0 mg
2. APL510 3.0 mg followed by APL510 1.5 mg followed by placebo
3. Placebo followed by APL510 3.0 mg followed by APL510 1.5 mg
Ease of withdrawal was assessed at the end of each treatment sequence, not each period. In addition, the number of night-time awakenings was not included in the updated version of the diary introduced during the study and only 50% of subjects were randomised to actigraphy.
Scientific Contact Details - Lead Principal Investigator:
Dr Douglas McKeith, MB ChB BSc MRCGP DRCOG DCCH
Formerly of Synergie Consultancy Limited
Unit 6.07 Kelvin Campus
West of Scotland Science Park
Glasgow, G20 0SP
United Kingdom
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Primary aim
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Total sleep time of subjects as recorded in sleep diaries. The primary comparison for efficacy was the average of the primary outcomes under the two APL510 doses (1.5 mg and 3 mg) versus placebo.
Measured throughout the study and the data was averaged or tabulated after completion of the study.
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Secondary Aim
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Secondary measures of efficacy revolved largely around the subjective scales employed. These were as follows:
1. Time to sleep onset
2. Number of night-time awakenings
3. Ease of getting to sleep
4. Sleep quality
5. Ease of awakening
6. Behaviour following wakening
Measured throughout the study and the data was averaged or tabulated after completion of the study.
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Participant Information Sheet
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Sorry, not currently available
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Website
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Sorry, not currently available
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Recruitment Status
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Completed
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Nation
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England
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Location
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Chippenham
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