Study to Investigate the Effects of Melatonin, Temazepam & Zolpidem on Sleep EEG in Men and Women

NCT00940550 | Completed Phase 1

• 1 other identifier: CRC 266
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study has been designed to compare the effects of melatonin with those of drugs (temazepam and zolpidem) regularly prescribed for the treatment of insomnia, in healthy, middle-aged volunteers. The study will take place at one centre. Volunteers consenting to participate in the study will have their eligibility confirmed by a screening panel, including spending one night in the sleep clinic to acclimatize to the study procedures. Blood and urine samples will be collected during this overnight visit. Volunteers continuing to remain eligible will receive, in turn, melatonin, temazepam, zolpidem and placebo as a single dose during 4 treatment phases lasting one night and separated by at least five days. Neither the volunteer nor the study staff will be aware of which drug each volunteer is receiving at each treatment phase. The volunteer's electrical brain activity will be measured whilst sleeping. Other aspects of sleep, including measures of sleep quality, will also be measured. Urine samples will be collected during each treatment phase. Volunteers will undergo an assessment of health prior to departure from the clinic at their last treatment phase, and study staff will telephone 2 weeks later to obtain further information on their health status. The primary study objective is to compare EEG power spectra during nonREM sleep in the slow-wave frequencies following administration with melatonin to temazepam.

Conditions

Insomnia

Outcome Measures

Primary Outcomes (1)

• EEG Power density in slow wave frequencies during NREM sleep

  Treatment Periods 1 to 4

Secondary Outcomes (1)

• EEG power density 0.25-32.0 Hz in NREM and REM sleep. EEG power density in the theta frequencies during the Karolinska Drowsiness Test. Objective polysomnography measures of sleep

  Treatment Periods 1 to 4

Study Arms (4)

Prolonged-release melatonin 2 mg

EXPERIMENTAL

Drug: Prolonged-release melatonin

Temazepam 20 mg

ACTIVE COMPARATOR

Drug: Temazepam

Zolpidem 10 mg

ACTIVE COMPARATOR

Drug: Zolpidem

Placebo

PLACEBO COMPARATOR

Drug: Placebo to match melatonin, zolpidem and temazepam

Interventions

Prolonged-release melatonin DRUG

2 mg tablet, once.

Prolonged-release melatonin 2 mg

Temazepam DRUG

20 mg capsule, once

Temazepam 20 mg

Zolpidem DRUG

10 mg capsule, once

Zolpidem 10 mg

Placebo to match melatonin, zolpidem and temazepam DRUG

Placebo to match melatonin: tablet, once. Placebo to match zolpidem: capsule, once. Placebo to match temazepam: capsule, once.

Placebo

Eligibility Criteria

• Age: 55 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject is able to read and understand the Informed Consent Form (ICF), and understand study procedures.
• The subject has signed the ICF.
• Healthy male or female subjects aged 55-64 years inclusive. Attempts will be made to achieve an equal gender ratio through appropriate screening procedures, but a failure to do so will not preclude analysis of the final data set.
• The subject has a history of the following sleep characteristics during the past three months or more at Visit 1:
• Bedtime between 22:00-00:00h on at least five nights per week
• Reported typical nightly sleep duration between 6.5 and 8.5 h
• The subject has a regular sleep-wake cycle and maintains a regular sleep-wake cycle during the study
• The subject is a non-smoker who has not used nicotine or nicotine-containing products for at least approximately 6 months. Subjects who have discontinued smoking or the use of nicotine/nicotine containing products for at least approximately 3 months may be enrolled in the study at the discretion of the investigator.
• The subject is, in the opinion of the investigator, healthy on the basis of a physical examination, medical history, vital signs, ECG, and the results of routine laboratory tests.

You may not qualify if:

• The subject is female AND of childbearing potential. Female volunteers will be considered not of child-bearing potential if they are:
• Pre-menopausal women who have been surgically sterilized by bilateral oopherectomy and/or hysterectomy, OR
• Post-menopausal, defined as:
• No spontaneous menstruation for at least one year prior to the first dose,
• Follicular stimulation hormone (FSH) \>18mIU/mL, AND
• Not lactating.
• The subject has a known sensitivity to temazepam, zolpidem or melatonin or a history of any allergy that in the opinion of the investigator would contraindicate subject participation.
• The subject has a BMI of less than 19, or more than 33kg/m or a total body weight of less than 50 kilograms at pre-study (screening) visit. BMI is calculated by taking the subject's weight in kg and dividing by the subject's height in metres, squared.
• The subject has a score of \>5 points on the Pittsburgh Sleep Quality Index (PSQI) scale.
• The subject has a history of clinically significant sleep pathology according to DSM-IV TRTM or presents symptoms of clinically significant sleep pathology at PSG screening. AHI of \>10 and PLMAI of \>10.
• The subject is a shift worker or maintains an irregular sleep-wake schedule during 1 month preceding the screening visit, or travelled within the last month preceding the screening visit and/or during the study to a time zone more than 2 hours different to the current time zone in Surrey.
• The subject consumes more than three (men) or two (women) units of alcohol per day on average over the 1 month preceding Visit 1(screening visit) \[NOTE: 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine\].
• The subject consumes more than 5 caffeine-containing beverages per day.
• Clinically significant psychiatric, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological (particularly myasthenia gravis), immunological, or haematological disease or abnormality, as determined by the study physician.
• History of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1.

Sponsors & Collaborators

• University of Surrey: lead
• H. Lundbeck A/S: collaborator

Study Sites (1)

Surrey CRC, University of Surrey, Egerton Road

Guildford, Surrey, GU2 7XP, United Kingdom

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Temazepam; Zolpidem

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Dr. Daryl Bendel, MBChB

  Surrey CRC

  STUDY DIRECTOR

• Dr. Malgorzata Knurowska, MD

  Surrey CRC

  PRINCIPAL INVESTIGATOR

• Professor Derk-Jan Dijk, Ph.D., B.S., M.S

  Surrey Sleep Research Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 15, 2009
• First Posted: July 16, 2009
• Study Start: July 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: August 8, 2011

Record last verified: 2009-11

Locations

GB (1)