Clinical trial NCT00626418 (phase 2, status: completed)
Conditions: restless legs syndrome
ICD codes: G25.81
Drugs: aplindore, placebo
SMILES: O=C1CC2=C3O[C@@H](CNCC4=CC=CC=C4)COC3=CC=C2N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Aged 18 years or older;

          -  Diagnosis of primary Restless Legs Syndrome (RLS) using ICSD-2 criteria:

          -  The patient reports an urge to move the legs, usually accompanied or caused by
             uncomfortable and unpleasant sensations in the legs.

          -  The urge to move or the unpleasant sensations begin or worsen during periods of rest
             or inactivity such as lying or sitting.

          -  The urge to move or the 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 the unpleasant sensations are worse, or only occur, in the evening
             or night.

          -  The condition is not better explained by another current sleep disorder, medical or
             neurological disorder, mental disorder, medication use, or substance use disorder.

          -  International Restless Leg Syndrome Study Group (IRLSSG) RLS rating scale score > 15
             at screening

          -  PLMI of greater than 10 per hour of total sleep time (TST) determined by PSG during
             the adaptation night;

          -  Body mass index (BMI) ≤ 35 kg/m2;

          -  In good general health as determined by a thorough medical history and physical
             examination (including vital signs), 12-lead ECG (lab tests mentioned below)

          -  Patients have clinical laboratory values within normal reference range or must not be
             clinically significantly abnormal as judged by the Investigator and approved by the
             Sponsor;

          -  Patients must be off all prescription drug therapy or OTC medication they may be
             taking for RLS as well as any other psychotropic medication for at least 5 half lives
             prior to adaptation night and off any investigational drug for at least 30 days;

          -  Patients taking prescription or over-the-counter medication for chronic medical
             conditions must be on stable doses of these medications for at least two weeks prior
             to participation in the study.

          -  If the patient is a female of childbearing potential, she must be using an acceptable
             method of contraception, must have a negative urine pregnancy test at screening, and
             must have a negative urine pregnancy test at the adaptation night. Acceptable methods
             of contraception are oral, intrauterine, implantable, injectable contraceptives or
             double barrier methods. After screening, patients using oral contraceptives must agree
             to add the double barrier method until 30 days following the last dose of study
             medication. Women on oral contraceptives must have been using them for at least one
             month prior to screening.

          -  Be able to read, understand, and provide written/dated informed consent before
             enrolling in the study, and must be willing to comply with all study procedures;

          -  Patients must be willing and able to be confined to the clinical research site for a
             period of 5 nights or more as required by the protocol.

          -  Patients must refrain from strenuous physical activity on the day of admission and on
             PSG days.

        Exclusion Criteria:

          -  Clinically significant unstable medical illness;

          -  Evidence or history of clinically significant allergic (except for untreated,
             asymptomatic, seasonal allergies at time of dosing), hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological
             disease;

          -  History of non-Basal Cell cancer within 5 years of screening;

          -  History of non-gestational diabetes within 5 years of screening;

          -  A supine blood pressure > 140/90 mm/Hg at screening or adaptation;

          -  Clinically significant psychiatric illness, including chronic psychiatric illness or
             the history or presence of any Axis I condition;

          -  History or presence of chronic pain other than that associated with RLS;

          -  History of epilepsy or serious head injury;

          -  Clinically significant sleep apnea, narcolepsy, parasomnia as an adult, circadian
             rhythm disorder, or secondary causes of RLS;

          -  An apnea-hypopnea index (AHI) > 10, as assessed by PSG during the adaptation night

          -  Any condition that may affect oral drug absorption;

          -  Travel across more than three time zones, an expected change in sleep schedules of 6
             hours or more, or involvement in night shift work within seven days prior to screening
             or during the study period;

          -  Any clinically significant abnormal finding on physical examination, vital signs, ECG,
             or clinical laboratory tests, as determined by the Investigator. (The QTcB interval
             must be ≤ 450 msec for males and ≤ 470 msec for females);

          -  History of allergies, or known sensitivity, hypersensitivity, or adverse reaction to
             any drug similar to aplindore;

          -  Pregnant or lactating females;

          -  Recent history (≤ one year) of alcohol or drug abuse, or current evidence of substance
             dependence or abuse as defined by DSM-IV criteria;

          -  Regular consumption of large amounts of xanthine-containing substances (i.e. more than
             5 cups of coffee or equivalent amounts of xanthine-containing substances per day);

          -  Self report of the usual consumption of more than 14 units of alcohol per week;

          -  Secondary causes of RLS which will be ruled out by physical exam, medical history and
             clinical chemistries, including serum ferritin;

          -  Use of any investigational drug within 30 days prior to screening;