EFFECTS OF PREGABALIN ON SLEEP MAINTENANCE IN SUBJECTS WITH FIBROMYALGIA SYNDROME AND SLEEP MAINTENANCE DISTURBANCE: A RANDOMIZED PLACEBO-CONTROLLED 2-WAY CROSSOVER POLYSOMNOGRAPHY STUDY

• Register: EUCTR
• Last refreshed on: 25 February 2013
• Main ID: EUCTR2009-011014-17-DE
• Date of registration: 18/05/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017, US
• Public title: EFFECTS OF PREGABALIN ON SLEEP MAINTENANCE IN SUBJECTS WITH FIBROMYALGIA SYNDROME AND SLEEP MAINTENANCE DISTURBANCE: A RANDOMIZED PLACEBO-CONTROLLED 2-WAY CROSSOVER POLYSOMNOGRAPHY STUDY
• Scientific title: EFFECTS OF PREGABALIN ON SLEEP MAINTENANCE IN SUBJECTS WITH FIBROMYALGIA SYNDROME AND SLEEP MAINTENANCE DISTURBANCE: A RANDOMIZED PLACEBO-CONTROLLED 2-WAY CROSSOVER POLYSOMNOGRAPHY STUDY
• Date of first enrolment: 26/08/2009
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011014-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Men or women of any race, at least 18 years of age.
3. Women of childbearing potential must be non-pregnant and non-lactating, must have a negative pregnancy test at screening and must agree to utilize a medically acceptable form of contraception. Non-vasectomized men must either abstain from sexual activity or use an acceptable form of contraception.
4. Understand and be willing to cooperate with study procedures, including scheduled visits, daily IVRS diary completion and PSG.
5. Meet the American College of Rheumatology (ACR) criteria for fibromyalgia at Screening (Visit 1).
6. Customary bedtime between 9 PM and midnight and rise between 5 and 9 AM.
7. Maintain a normal daytime-awake, nighttime–asleep schedule, including approximately 6.5-8.5 hours each night in bed, and less than 3 hours variation in night-to-night bedtime for the past month prior to Screening (Visit 1).
8. Have clinically disturbed sleep on interview, reflected by difficulty in maintaining sleep at least 3 times per week for at least one month and meet Research Diagnosis Criteria (RDC) for insomnia disorder.


Self Report Sleep Inclusion Criteria (to be confirmed by Visit 3):
A minimum of 5 daily IVRS diary data points are required from Visit 2.

9. Self report Total Sleep Time (sTST) =6.0 hours for at least 3 nights/week during the screening period (IVRS diary).
10. Self-report wake time after sleep onset (sWASO) totaling at least 60 minutes for at least 3 three nights/ week during the screening period (IVRS diary).

PSG Sleep Inclusion Criteria (Visit 3):

11. Mean WASO >45 minutes calculated on each of the 2 PSG nights with neither night WASO <30 mins.
12. TST of between 3 and 6.5 hours on each of the 2 PSG nights.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.History of any active sleep disorder other than RDC insomnia disorder.
2.History of any sleep or circadian rhythm sleep disorder incl. RLS, narcolepsy, sleep apnea, phase advance or delay syndromes within the past 5 years.
3.Taking CNS active medication known to affect sleep wake function (within 5 half lives), or unable to wash out of prohibited medications by Visit2. (Note: stable SSRI antidepressant usage, in cases where sleep disturbance preceded and is not secondary to antidepressant use is permitted per allowed/prohibited medication list.)
4.Currently on or planning to be involved in night/rotating shift work or traveling across more than 4 time zones in 14 days prior to screening, plan to travel across time zones during the study, regular napping (or any after 6PM), or regular disruptions during the night (such as care for dependents).
5.Clinically significant depression or other DSM-IV Axis I disorder (as determined by psychiatric exam and/or Mini International Neuropsychiatric Interview, version 6.0; [MINI]) that would confound assessment of sleep or make the subject inappropriate for a clinical trial.
6.Imminent risk for self-injurious/suicidal or violent/homicidal behavior, as deemed by the investigator.
7.Any clinically unstable hematological, autoimmune, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disorder.
8.Substance abuse in the last 6 months and dependence in the last year (other than nicotine).
9.Current or within the last 6 months, white blood cell count of <2500 cells/µL or a neutrophil count of <1500 cells/µL or a platelet count of <100x103 cells/µL, or a history of bone marrow suppression.
10.Clinically significant liver disease, which may prevent the patient from completing the study or an elevation in either bilirubin, aspartate aminotransferase, or alanine aminotransferase of greater than 3 times the maximum value of the laboratory assay normal range. Laboratory assays may be repeated once prior to baseline to confirm the unacceptability of any patient.
11.Hypothyroidism, hyperthyroidism, or laboratory findings consistent with these disorders. Exceptions are patients who are euthryroid and have been on stable doses of thyroid replacement for six months or more.
12.CLcr =60 mL/min (estimated from serum creatinine or 24 hour CrCl).
13.Participation in any clinical trial within the 30 days before Screening and/or during study participation.
14.Previous participation in a clinical study of pregabalin; intolerance or failure to respond to therapeutic doses of gabapentin or pregabalin or other alpha-2-delta agonist, including sleep disturbance on doses of >2000 mg/day gabapentin, per medical history; pregabalin within 60 days prior to Screening.
15.Use of alcohol as a sleep aid, or more than 2 standard drinks consumed per day, or more than 14 consumed per week, except for isolated instances.
16.Excessive caffeine use over the last 3 months, except for isolated instances.
17.Excessive cigarette or cigar smoking over the last 3 months.
18.Positive urine drug screen for any of the following substances or classes of compounds: amphetamines, barbiturates, opiates, benzodiazepines, sedatives and hypnotics, cocaine, phencyclidine (PCP), cannabinoids, or other drugs of abuse. As the protocol allows for a seven-day washout period prior to Visit2 for current sleep medications (benzodiazepines, sedatives and hypnotics), positive results for these sleep aid medications will be allowed for Visi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

SLEEP MAINTENANCE IN SUBJECTS WITH FIBROMYALGIA SYNDROME AND SLEEP MAINTENANCE DISTURBANCE
MedDRA version: 9.1 Level: LLT Classification code 10016631 Term: Fibromyalgia syndrome

Intervention(s)

Trade Name: LYRICA 75 mg Capsules
Product Name: Pregabalin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148-553-50-8
Other descriptive name: (S)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: LYRICA 150 mg Capsules
Product Name: Pregabalin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148-553-50-8
Other descriptive name: (S)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: LYRICA 225 mg Capsules
Product Name: Pregabalin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148-553-50-8
Other descriptive name: (S)-3-(aminomethyl)-5-methylhexanoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 225-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • To demonstrate the effect of pregabalin compared to placebo on sleep maintenance as measured by WASO obtained by PSG in patients with fibromyalgia and sleep maintenance disturbance.

Secondary Objective: • To characterize the effect of pregabalin on other measures of sleep maintenance in patients with fibromyalgia using PSG, including: TST, SE, NAASO, WTDS, WTAS, LPS, and SWS
• To investigate the effect of pregabalin on overall sleep problem index and sleep disturbance (as measured by specific MOS-SS subscales and NRS sleep quality score)

• To characterize the effect of pregabalin on sleep maintenance as determined by subject- rated assessments of WASO (sWASO) and total sleep time (sTST), latency to sleep onset (LSO); and pain, as determined by NRS pain score

• To investigate the safety and tolerability of pregabalin in patients with fibromyalgia and sleep disturbance.

Primary end point(s): The primary endpoint in this study is the mean WASO (as determined by PSG assessment) from two consecutive nights in the last visit of each treatment period. The primary endpoint will be analyzed using a linear mixed effects model including sequence, period, and treatment as fixed factors and subject within sequence and within-subject error as random factors. The point estimate for mean treatment difference (pregabalin-placebo) and 95% confidence intervals (CIs) for the true mean treatment difference will be reported. Descriptive statistics will also be reported for the primary efficacy endpoint by visit and treatment group.
The primary analysis will be performed on the per-protocol population of subjects reaching the approved treatment dose of 300-450 mg/day. Subjects not able to tolerate those doses will be included in the safety population, and in a full analysis set.

Secondary ID(s)

A0081165