Insomnia and Osteoarthritis Study

Inclusion Criteria:

- Age 18-64

- Diagnosed with and under physicians care for osteoarthritis of the knee according to
American College of Rheumatology Criteria with radiographic evidence demonstrating at
least grade 1 osteoarthritis (OA)

- Report at least typical arthritic pain>4 out of 10 (0=no pain, 10=the most extreme
pain imaginable)

- Meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and International
Classification of Sleep Disorders, Revised definition (ICSD-R) criteria for either
primary (psychophysiologic) insomnia or insomnia secondary to osteoarthritis

- Insomnia symptoms must include problems with middle of the night awakenings

- Insomnia symptom duration > 6 months

- Baseline, 2-week, sleep diary average wake after sleep onset time >30 minutes

- Baseline self-reported total sleep time < 6.5 hours per night

- Patients taking NSAID therapy for pain must be on a stable dose for a period of at
least one month prior to initiating the study

Exclusion Criteria:

- Intrinsic sleep disorders other than insomnia (sleep apnea, periodic limb movement
disorder, etc)

- Significant rheumatologic or chronic pain disorders other than osteoarthritis of the
knee, including fibromyalgia or the complaint of widespread pain impacting 4
quadrants, complex regional pain syndrome, post herpetic neuralgia, etc)

- Major medical disease (including, hepatic impairment, chronic obstructive pulmonary
disease/compromised respiratory function, cancer, dementia, diabetes, congestive heart
failure, cerebrovascular disease, raynaud's syndrome)

- Active major psychiatric disorders (including dementia or cognitive impairment) and
history of schizophrenia or bipolar I disorder

- History of serious suicide attempt; 6) history of alcohol or substance (including
prescription medications) abuse

- Pregnancy or plans to become pregnant within 6 months

- Intraarticular steroid injection within the past month

- Regular (>3 days/week) use of antidepressants, antipsychotics, and mood stabilizers,
within the past two months

- Regular (> 3/week) use of myorelaxants, narcotics, sedative hypnotics, and
anticonvulsants within the past one month

- Unwilling or unable to discontinue all use of the medications listed in #10 for two
weeks prior to starting the study

- Unwilling or unable to discontinue all centrally acting agents and all analgesic usage
within 24 hours of pain testing sessions

- Refusal to provide consent to contact patient's physician to establish diagnosis and
obtain medical record information

- Regular tobacco or nicotine use

- Heavy caffeine use [(>2 cups of coffee/day (equivalent)

- History of previous allergic reaction or severe side effects to sedative hypnotics

- Use of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin,
troleandomycin, ritonavir, nelfinavir)

- In addition, subjects will undergo in-laboratory blood tests prior to receiving drug
and will be excluded from further participation if they exhibit: a) positive pregnancy
test, b) positive toxicology (benzodiazepine, opioids, Tetrahydrocannabinol (THC),
alcohol, and stimulants), c) abnormal liver enzyme panel