E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SLEEP MAINTENANCE IN SUBJECTS WITH FIBROMYALGIA SYNDROME AND SLEEP MAINTENANCE DISTURBANCE |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016631 |
E.1.2 | Term | Fibromyalgia syndrome |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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. |
|
E.2.2 | Secondary objectives of the trial |
• 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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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 Visit 1 only. Subjects testing positive on breathalyzer for ethanol prior to randomization (ie, at Visit3) are to be excluded. Subjects testing positive after randomization should be evaluated for continuation based upon investigator judgment and subject's prior behavior. 19.Subjects with life-threatening neoplasm within the 2 years prior to Screening, or any history of neoplasm not considered in remission. Cured basal cell or squamous cell carcinoma of the skin is allowed, as are treated conditions with no recurrence, or in remission. 20.Clinically significant abnormal screening electrocardiogram. 21.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 22.Subjects with pending Worker's Compensation, Worker's Compensation, civil litigation or disability claims pertinent to subjects' fibromyalgia; current involvement in out-of court-settlements for claims pertinent to subjects' fibromyalgia; or currently receiving monetary compensation as a result of any of the preceding. 23.An apnea-hypopnea index >10 on either night of PSG. 24.Periodic limb movement with arousal index >10 on either night of PSG. 25.LPS of <10 minutes on either PSG night. |
|
E.5 End points |
E.5.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |