The Effects of Aplindore on the Treatment of Signs and Symptoms of Restless Legs Syndrome

NCT00626418 | Completed Phase 2

• 1 other identifier: Aplindore-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to assess the efficacy and tolerability of single doses of aplindore compared to placebo in RLS. Patients will be required to spend 5-8 nights in a sleep laboratory. This includes 1 adaptation night, 1 placebo night, and 3-6 drug treatment nights. Ascending doses of active drug will be administered on study nights 3 through 5 to determine the maximum well tolerated efficacious dose (defined as a decrease in Periodic Limb Movement Index (PLMI) of at least 50% from placebo baseline). If an efficacious dose cannot be identified the Investigator in consultation with the sponsor may decide to examine higher doses in up to 3 additional PSG nights in an attempt to identify a tolerable efficacious dose. This study will utilize up to 24 evaluable patients, each meeting International Classification of Sleep Disorders (ICSD-2) diagnostic criteria for primary RLS who are not currently taking any RLS medication including DAs ( and L-dopa) or who are able to discontinue their RLS medication at least 5 half-lives prior to the adaptation night.

Conditions

Restless Legs Syndrome

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy and tolerability of single doses of aplindore compared to placebo in RLS.

  5-8 Days

Secondary Outcomes (1)

• To generate safety data with aplindore, to generate pilot data on the effects of aplindore on changes in blood pressure and heart rate associated with PLMS in patients with RLS, to understand the PK of aplindore.

  5-8 Days

Study Arms (2)

1

PLACEBO COMPARATOR

This will be a crossover study. Ascending doses of active drug will be administered on study nights 3-5 with an option of 3 additional nights in an attempt to identify a tolerable efficacious dose. Night 1 will be an adaptation night and night two will be a placebo night.

Drug: Placebo

2

ACTIVE COMPARATOR

This will be a crossover study. Ascending doses of active drug will be administered on study nights 3-5 with an option of 3 additional nights in an attempt to identify a tolerable efficacious dose. Night 1 will be an adaptation night and night two will be a placebo night.

Drug: Aplindore

Interventions

Aplindore DRUG

Tablets 0.05, 0.1, 0.2, 0.3, 0.5 and 0.7 mg QD for up to 6 nights

2

Placebo DRUG

Placebo tablets

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Ligand Pharmaceuticals: lead

Study Sites (5)

MD Clinical

Hallandale, Florida, 33009, United States

Location

Sleep Disorders Center of Georgia

Atlanta, Georgia, 30342, United States

Location

Community Research

Crestview Hills, Kentucky, 41017, United States

Location

Clinilabs, Inc.

New York, New York, 10019, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

aplindore fumarate

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2008
• First Posted: February 29, 2008
• Study Start: February 1, 2008
• Primary Completion: October 1, 2008
• Last Updated: October 3, 2011

Record last verified: 2011-09

Locations

US (5)