Recruiting
Phase 2

Levotofisopam

Sponsor:

Pharmos

Code:

NCT01519687

Conditions

Hyperuricemia

Gout

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

levotofisopam

Study Details

Brief summary:

The purpose of this study is to determine whether levotofisopam is safe and effective in the treatment of hyperuricemia and gout.

Conditions

Hyperuricemia

Gout

Study ID

NCT01519687

Start date

Jan, 2012

Status verified date

Jan, 2012

Completion date

Jun, 2012

Anticipated

Primary completion date

Jun, 2012

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Provide voluntary, signed informed consent.
  • Male or postmenopausal or surgically sterile females, 18 to 65 years of age, inclusive. Female participants must have been amenorrheic for a minimum of 12 months and must have a negative pregnancy test result within 3 days before administration of levotofisopam. Surgically sterile females are defined as those who have had a hysterectomy, bilateral ovariectomy, or bilateral tubal ligation. Male subjects must agree to practice a medically acceptable form of contraception for the duration of the study and for 30 days after receiving the last dose of levotofisopam.
  • Physician diagnosis of gout with at least one gout flare in the last 6 months, at least one chronically swollen joint due to gout, or presence of a tophus.
  • Serum urate level ≥ 8.0 mg/dL and ≤ 12.0 mg/dL after having stopped all urate-lowering therapy for at least 10 days. Serum urate level must also be > 7.7 mg/dL and ≤ 12.0 mg/dL on Day -3 and on Day -2.
  • Willing and able to discontinue urate-lowering therapy starting at the screening visit (14-21 days before receiving study drug) through to the follow-up visit (up to 10 days after discharge from the study unit), for a total time off urate-lowering therapy of up to approximately 5 weeks.
  • In the opinion of the investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant.
  • Medications permitted for the treatment of non-excluded medical conditions (other than gout) must be at stable doses for at least 14 days prior to baseline.
  • Permitted concurrent general medical conditions must be stable and well controlled.
  • Written and oral fluency in the English language.

Exclusion Criteria:

  • Previous treatment with racemic tofisopam (RS-tofisopam), levotofisopam (S-tofisopam), or dextofisopam (R-tofisopam).
  • Known or suspected hypersensitivity to any benzodiazepine.
  • History of two or more clinically significant drug allergies.
  • Clinically significant infection within 30 days prior to screening or between screen and admission.
  • History or presence of clinically significant medical disease that might compromise the study or be detrimental to the patient, such as hepatitis (patient excluded if hepatitis A was present within 2 years before screening or if there is any history of hepatitis B or C), human immunodeficiency virus (HIV) infection, uncontrolled diabetes mellitus, cirrhosis, active biliary disease (bile ducts or gallbladder), or moderate or severe chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2).
  • Presence of a gout flare during screening or the procedure window.
  • History or presence of nephrolithiasis.
  • History or presence of malignancy other than localized basal cell cancer, squamous cell skin cancer, or cancer in situ that has been resected within 5 years.
  • Clinically significant head trauma with loss of consciousness within 10 years prior to screen.
  • Myocardial infarction, congestive heart failure, or known coronary artery disease within 5 years prior to screen.
  • Any history of cerebrovascular accident.
  • History of seizure disorder other than a single childhood febrile seizure.
  • Alcohol or psychoactive substance abuse or dependence, as defined by DSM-IV, within 1 year prior to screen, or alcohol use exceeding 21 units per week (on average) in the 3 months preceding screen.
  • Used any tobacco- or nicotine-containing product more days than not within 30 days prior to screening or between screen and admission.
  • Regular consumption (e.g., more days than not) of excessive quantities of caffeine-containing beverages (e.g., more than eight cups of coffee or equivalent per day) within 30 days prior to screening or between screen and admission.
  • History of suicide attempt, any suicidal behavior within 6 months prior to screening or between screen and baseline, or, in the opinion of the investigator, clinically significant risk of suicide or violent behavior.
  • History or presence of a clinically significant psychiatric disorder or symptom (e.g., delusions, hallucinations) that is likely to compromise the study (e.g., confound study results) or be detrimental to the patient.
  • History of difficulty donating blood, or history or presence of clinically significant bleeding or hemorrhagic tendencies.
  • Donation of blood or plasma within 90 days prior to screening or between screening and admission.
  • Uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 95 mmHg) or heart rate either < 50 BPM or > 100 BPM at any evaluation prior to the first dose of test drug.
  • Pregnancy, lactation, a positive pregnancy test result during the screening or admission evaluation.
  • A clinically significant abnormality on the screening physical examination, 12-lead electrocardiogram (ECG), or laboratory evaluations.
  • A corrected QT (QTcF) value > 450 msec (males) or > 470 msec (females) at screening, admission (Day -3), or baseline (Day -1).
  • Aspartate aminotransferase or alanine aminotransferase levels > 2 times upper limit of normal (ULN), alkaline phosphatase > 1.5 times ULN, creatinine outside the limits of normal, triglycerides > 500 mg/dL, or thyroid-stimulating hormone (TSH) levels greater than 6.0 µIU/L at screening, admission (Day -3), or Day -2.
  • A finding of opiates, amphetamines, cocaine, cannabis, or phencyclidine on the urine drug screen (UDS). Any other positive UDS result must be discussed by the investigator and medical monitor prior to potentially allowing participation of the subject in the study.
  • A positive HIV, hepatitis B, or hepatitis C test.
  • Inability to take or tolerate colchicine for gout flare prophylaxis (0.6 mg QD or BID).
  • Required use of any of the following from the screening visit through the follow-up visit: aspirin or other nonsteroidal antiinflammatory drugs (other than paracetamol, as noted below), diuretics, medications with known urate-lowering effects (including, but not limited to, fenofibrate, losartan, or vitamin C > 500 mg/day), or urate-lowering therapy other than levotofisopam.
  • Dietary requirements inconsistent with the study unit's standardized diet.
  • Body mass index ≥ 35.
  • Use of any investigational treatment within 30 days prior to screening or between screen and admission.
  • Use of any psychopharmacologic drug or substance within 7 days of screening or between screen and admission.
  • Use of potent CYP3A4 inhibitors or potent CYP3A4 inducers within 7 days prior to screening or between screen and admission.
  • An estimated 24-hour uric acid excretion > 1,000 mg/day.

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Levotofisopam

All patients will receive a single dose of 50 mg on Day 1, 50 mg three times a day (TID) on Days 2 through 6, and a single dose of 50 mg on Day 7. Each dose of study drug will be administered by authorized site personnel throughout the 7-day inpatient treatment period.

Interventions

levotofisopam

50 mg on Day 1, 50 mg TID on Days 2 through 6, and a single dose of 50 mg on Day 7

Primary outcome measure

  • Percentage reduction in serum urate [ Time Frame: Days 1-7 ]

Central Contacts and Locations

Central contacts

John S. Sundy, MD, PhD

(919) 684-2347john.sundy@duke.edu

Lou Cappoli, MBA

(919) 684-4888lou.cappoli@duke.edu

Locations

Duke Clinical Research Unit (DCRU)

Recruiting

Durham, North Carolina, United States, 27720

Contacts

John S. Sundy, MD, PhD

919-684-2347john.sundy@duke.edu

Lou Cappoli

(919) 684-4888lou.cappoli@duke.edu

Principal Investigator:

John S. Sundy, MD, PhD

More Information

Sponsor

Pharmos

Last update posted

Jan 27, 2012

Last verified

Jan, 2012

Keywords

  • hyperuricemia
  • gout
  • levotofisopam

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Pharmos on 2012-01-27.