Contact information
Type
Scientific
Primary contact
Ms Rebecca Scoble
ORCID ID
Contact details
Alliance Pharmaceuticals Ltd
Avonbridge House
Bath Road
Chippenham
SN15 2BB
United Kingdom
-
medinfo@alliancepharma.co.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
APL510-009
Study information
Scientific title
A double-blind placebo controlled crossover study to determine if melatonin can improve the length of day time sleep in subjects with transient misalignment of the sleep-wake cycle as a result of working permanent night-shifts
Acronym
Study hypothesis
The primary objective was to determine if APL510 tablets (containing 1.5 mg of melatonin) increased the length of daytime sleep following a night-shift.
The secondary objectives were:
1. To determine if APL510 tablets increased the maintenance of daytime sleep and reduced sleep latency and the number of episodes of disturbed sleep following a night-shift
2. To determine if APL510 had any 'residual' effect during the night-shift work period
3. To compare the adverse event (AE) profiles of APL510 and placebo
The trial was previously registered at Pharmaceutical Industry Clinical Trials Database (ABPI/CMR) - https://www.cmrinteract.com/clintrial/default.htm.
Ethics approval
South Birmingham Research Ethics Committee, 04/04/2005, ref: 05/Q2707/56
Study design
Single centre double-blind placebo-controlled two-way crossover study
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Condition
Insomnia
Intervention
This was a single centre, double-blind, placebo-controlled, two-way crossover study. Subjects included in the study worked one of two shift patterns: 4 nights working followed by 4 nights not working ("4 nights on, 4 nights off") and 3 nights working followed by 4 nights not working ("3 nights on, 4 nights off").
Subjects were randomised to one of two treatment sequences: either placebo followed by APL510 1.5 mg or APL510 1.5 mg followed by placebo. Subjects took study medication for one work shift period and then crossed over to the next randomised treatment. Subjects attended their final visit at the end of their second treatment period, although a further follow-up visit was available during the next work shift period for subjects who had ongoing adverse events (AEs) at the end of the second treatment period.
Scientific Contact Details - Lead Principal Investigator:
Dr Paul Kanas BM BS, MRCP, FFOM
Cadbury Trebor Bassett
Bournville
Birmingham, B30 2LU
United Kingdom
Intervention type
Drug
Phase
Phase II
Drug names
APL510
Primary outcome measures
Mean total sleep time over the days on which diary entries were recorded.
Measured throughout the study and the data was averaged or tabulated after completion of the study.
Secondary outcome measures
1. Mean number of daytime awakenings
2. Potential hangover effects
Measured throughout the study and the data was averaged or tabulated after completion of the study.
Overall trial start date
10/10/2005
Overall trial end date
19/04/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Male or female subjects aged 18 to 65 years working permanent night-shifts with at least three consecutive night-shifts in their shift pattern
2. A female subject could be included if:
2.1. She was of non-child-bearing potential (e.g., post-menopausal for 1 year, had undergone bilateral tubal ligation, had undergone a hysterectomy or was physiologically incapable of becoming pregnant), or
2.2. She was of childbearing potential practising an acceptable method of birth control defined as the use of oral or depot hormonal contraception, an intrauterine contraceptive device or a combination of both spermicidal and barrier methods of contraception (a partner having had a vasectomy was not an acceptable reason for inclusion), or
2.3. Total abstinence from sexual intercourse was maintained
3. Provided written informed consent
4. No planned absences from work, other than rest days, for the duration the subject was in the study. Subjects could work additional night-shifts as overtime
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
44 evaluable subjects
Participant exclusion criteria
1. 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 or other clinically relevant abnormality which in the opinion of the Investigator would preclude successful participation in the study
2. A recent history (less than 2 years) of alcohol or drug abuse or current evidence of substance dependence or abuse as defined by Diagnostic and Statistical Manual of Mental Disorders-IV criteria, with the exception of nicotine dependence
3. Female subjects who were pregnant, not using an adequate form of contraception or breast-feeding
4. Subjects receiving vitamins B6 and B12 supplements (excluding multivitamin supplements at recommended dose)
5. Subjects with a known hypersensitivity to melatonin or any of the excipients in the formulation
6. Subjects receiving hypnotics, tricyclic antidepressants, monoamine oxidase inhibitors, serotonin reuptake inhibitors, lithium, beta-blockers, calcium channel blockers, central alpha-blockers, non-steroidal anti-inflammatory drugs (excluding occasional over-the-counter use), alprazolam, triazolam, neuroleptics, or barbiturates. Subjects receiving any of these compounds were eligible for entry provided the medication was stopped 2 weeks prior to study entry.
7. Subjects with a known history of impaired hepatic or renal function defined as transaminases greater than 2 x the upper limit of normal or creatinine clearance of less than 35 mL/min
8. Subjects with a known severe allergic or auto-immune disease (e.g., multiple sclerosis, rheumatoid arthritis, severe asthma and systemic lupus erythematosus)
9. Subjects who had received an experimental drug within the previous 3 months
10. Subjects using melatonin
11. Subjects, who, by virtue of the need to care for close family members, might have been subjected to intermittent disturbance during their daytime rest periods
12. Subjects who, in the opinion of the Investigator, were not capable of completing the study
13. Subjects who did not consent to their General Practitioner being informed of their participation in the study
Pregnant or breast feeding women were excluded as the preclinical data on melatonin in this group were not available at the start of the study. Subjects were advised that caution should be exercised when driving or operating any heavy or dangerous machinery within 6 hours of taking a dose of study medication.
Recruitment start date
10/10/2005
Recruitment end date
19/04/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Alliance Pharmaceuticals Ltd
Chippenham
SN15 2BB
United Kingdom
Sponsor information
Organisation
Alliance Pharmaceuticals Ltd (UK)
Sponsor details
Avonbridge House
Bath Road
Chippenham
SN15 2BB
United Kingdom
+44 (0)1249 466966
info@alliancepharma.co.uk
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Alliance Pharmaceuticals Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary