Xyrem(Sodium Oxybate) and Ambien(Zolpidem Tartrate) in the Treatment of Chronic Insomnia.

Xyrem(Sodium Oxybate) and Ambien(Zolpidem Tartrate) in the Treatment of Chronic Insomnia: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study.

The primary purpose of the study is to evaluate the long term efficacy of sodium oxybate (Xyrem®) and zolpidem tartrate (Ambien®) in treating chronic insomnia. We will compare the efficacy of sodium oxybate with zolpidem tartrate (Ambien®), and compare the efficacy of each of these two medications with placebos.

Primary aim:

1. To assess the long term efficacy of sodium oxybate and zolpidem tartrate in reducing insomnia and improving sleep quality as assessed by a range of self-reported measures.

Questionnaires and Rating Scales: Subjects completed the following questionnaires and scales: Insomnia Severity Index, Epworth Sleepiness Scale (ESS), Beck Depression Inventory, Pittsburgh Sleep Quality Index (PSQI), Profile of Mood States-Fatigue (POMS). These questionnaires were administered at study baseline, treatment week 4, 8 and 12.

Clinical Global Impression (CGI). The CGI is a clinician-rated scale composed of two subscales that measure disease severity and degree of change, respectively. CGI-Severity (CGI-S) is a single-item, global scale of disease severity that requires the investigator to compare the patient's symptoms with those of all other patients who have the disorder. It is scored from 1 (normal) to 6 (among the most extremely ill of patients). CGI-Change (CGI-C) is a single-item scale of symptomatic improvement or worsening that requires the investigator to compare the patient's status at the time of assessment with baseline severity (baseline CGI-S). One study investigator performed all CGI-S and CGI-C ratings for all subjects.

Randomization. After completing all baseline procedures, eligible subjects were randomized to receive either a combination of active SXB and placebo ZOL (pZOL), active ZOL and placebo SXB (pSXB), or pSXB and pZOL, in a 1:1:1 parallel double-dummy design. A member of the study team who had no contact with subjects and no other role in this study was responsible for preparing study medications according to a randomization schedule. ZOL was encapsulated in lactose powder filled gelatin capsules to be indistinguishable from placebo capsules. Liquid pSXB was designed to match active SXB in appearance, taste and consistency. Subjects were given both liquid and capsule study medications, to maintain the double dummy design. Due to the flexible dose design of this study, subjects and investigators were not blinded to the dosages of study medication/placebo. All subjects were instructed to start study medication at 2.25 grams of SXB/pSXB and 5mg of ZOL/pZOL at bedtime. One study investigator reviewed all potential known side effects of SXB and ZOL prior to dosing, and subjects were instructed to take study medications at the bedside immediately before attempting to sleep, as is the standard administration for SXB.

Inclusion Criteria:

1. Written informed consent is obtained.
2. The patient is an outpatient, man or woman of any ethnic origin, 18-75 years of age (inclusive).
3. Patient reports insomnia for at least six months, and insomnia causes the patient distress.
4. The Investigator determines that the patient meets diagnostic criteria for Chronic Insomnia according to International Classification of Sleep Disorders (ICSD) criteria.
5. Sleep diary based screening shows sleep onset latency >30 minutes, and /or wake after sleep onset >30 minutes per night at least 3 nights per week, with combined wake-time-in-bed _> 45 minutes.
6. The patient is in good health as determined by a medical and psychiatric history, and physical examination.
7. Women must be surgically sterile, 2 years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control, and agree to continued use of this method for the duration of the study.
8. The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.

Exclusion Criteria:

1. Has any clinically significant, uncontrolled medical or psychiatric conditions. (treated or untreated)
2. Has a probable diagnosis of a current sleep disorder other than Chronic Insomnia.
3. Used any prescription drugs disallowed by the protocol or clinically significant use of over-the counter(OTC) drugs within 14 days before the screening visit.
4. Has a history of alcohol, narcotic, or any other abuse as defined by the DSM-V.
5. Has a clinically significant deviation from normal in the physical examination.
6. Is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)
7. Has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery and succinic semialdehyde dehydrogenase deficiency)
8. Has a known clinically significant drug sensitivity to sodium oxybate or sedative hypnotics.