Butrans for Treatment of Restless Legs Syndrome

• Subject has a diagnosis of RLS, defined by International Restless Legs Study Group (IRLS) essential criteria:

  • An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.
  • The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.
  • The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
  • The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night.
• Subject has moderate to severe RLS symptoms,defined as an International Restless Legs Scale (IRLS) score greater than or equal to15 at the baseline visit (visit 2).
• Subject has RLS symptoms that, in the opinion of the investigator, require round-the-clock treatment.
• Subject speaks and reads English.
• Subject is able to provide informed consent.
• Subject is age ≥25 and ≤75.
• Subject has BMI ≥18 and ≤35
• Subject is naïve to opioid treatment, defined as subjects not having received ≥5 mg oxycodone in the past 14 days and no history of daily use of ≥5 mg oxycodone equivalents in the past 3 months.
• If subject is currently being treated for RLS, s/he must have an inadequate response to or be intolerant of current, non-opioid regimen.
• If subject is not currently being treated for RLS, s/he must have a contraindication to or a history of intolerance to non-opioid treatment options for RLS, concerns about side effects of such options, or a preference for non-oral medication.
• If subject is currently being treated with a medication for RLS, a washout period of at least 3 days will be required (or 5 half-lives for longer-acting agents).
• Subject's history and/or clinical records document no change in medications active in the central nervous system (antidepressants, analgesics, antipsychotics, antiepileptics, hypnotics, etc.) for at least 30 days prior to visit 1.
• Subject is able to understand study procedures and agrees to remain on stable medications during the period of the study.
• Women of childbearing potential must agree to use a medically accepted method of birth control. Acceptable forms of birth control include:
• Condom + spermicide
• Diaphragm + spermicide
• Oral contraceptive pills, hormone implants (like Norplant), or injections(like Depo-Provera)
• Intrauterine Device

Exclusion Criteria:

• Lifetime history of DSM-IVopiod, alcohol, or other substance abuse.
• History of opioid treatment for RLS with inadequate response
• Positive urine toxicology screen at visit 1.
• Another chronic pain syndrome that would, in the opinion of the investigator, interfere with evaluation of RLS symptoms or the response to the study medication.
• Plan to undergo a procedure that may require short or long-term opiates for pain control during the course of the trial.
• History of severe mental illness.
• Women who are pregnant, lactating, or planning to become pregnant.
• Shift work or other commitments that do not allow for regular sleep at night.
• Known hypersensitivity or intolerance to opioids.
• History of Long QT Syndrome or an immediate family member with this condition, or known prolongation of QTc interval.
• QTc interval prolongation >500 ms on screening EKG at Visit 1.
• History of malignant melanoma.
• Current use of monoamine oxidase inhibitors.
• Prior or current clinically significant impulse control disorder, as determined by clinical interview and the Modified Minnesota Impulse Disorders Interview at Visit 1.8
• Untreated severe sleep apnea, defined as AHI >30.
• Iron deficiency, defined as ferritin\<15 at Visit 1.
• Any dermatologic condition resulting in widespread compromise of skin integrity, defined as >50% of the surface area within the 8 sites described for BTDS application.
• Current use of class IA or class III anti-arrhythmic medication.
• Significant risk for suicide by clinical interview.
• Known hypersensitivity to buprenorphine or any excipient of BTDS.
• Current unstable medical illness.
• Any medical or psychiatric condition that, in the opinion of the investigator, would interfere with participation in the study.