Clinical trial NCT00760955: Efficacy and Safety of TAK-583 in Subjects With Diabetic Peripheral Neuropathy
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging, Study to Evaluate the Efficacy and Safety of 3 Doses of TAK-583 in Subjects With Mild to Moderate Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Neuropathies
Keywords: Asymmetric Diabetic Proximal Motor Neuropathy
Diabetic Amyotrophy
Diabetic Autonomic Neuropathy
Diabetic Polyneuropathy
Neuralgia, Diabetic
Symmetric Diabetic Proximal Motor Neuropathy
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-09-26
Enrollment: 338
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of TAK-583, once daily (QD), in the treatment of neuropathy caused by diabetes mellitus.

Detailed description: Diabetic polyneuropathy is a frequent complication in individuals with type 1 and 2 diabetes mellitus, and can result in progressive functional and structural deficits in both somatic and autonomic nerves. Diabetic polyneuropathy is characterized by degenerative changes in nerve fibers resulting in progressive functional and structural deficits in both somatic and autonomic nerves.

TAK-583 is a synthetic compound currently under development for the treatment of diabetic polyneuropathy. The purpose of this study is to evaluate the safety and efficacy of TAK-583 for the treatment of mild to moderate diabetic polyneuropathy in subjects with type 1 or type 2 diabetes mellitus. Study participation is anticipated to be about 8 months.

Eligibility criteria: Inclusion Criteria:

* Female subjects must be post-menopausal or status post documented hysterectomy and bilateral oophorectomy.
* Has fasting clinical laboratory evaluations within the normal reference range for the testing laboratory, or if not, the results must be deemed not clinically significant by the investigator prior to randomization.
* Has Type 1 or type 2 diabetes, as defined by World Health Organization Criteria.
* Has mild to Moderate Diabetic Peripheral Neuropathy defined as:

  * Confirmed abnormality of at least two nerve conduction velocity parameters as defined by the Neurological Core Laboratory.
  * Sural sensory nerve potential amplitude greater than or equal to 1 μV (microvolt).
* Has glycosylated hemoglobin less than or equal to 10%.
* Is on stable pain medications for at least 3 weeks prior to randomization, if applicable.
* Has a glomerular filtration rate calculated by Modification of Diet in Renal Disease of greater than or equal to 45 mL/min/ body surface area.
* Spot albumin/creatinine ratio of less than 300 mg/g creatinine or 33.9 mg/mmol creatinine.
* Has acceptable clinical laboratory test results as defined by:

  * Hemoglobin Greater than or equal to 9.0 g/dL or 5.58 mmol/L
  * Thyroid stimulating hormone Within normal limits
  * Free T4 index Within normal limits
  * B12 level Within normal limits
* Is willing to follow an American Diabetes Association or similar recommended dietary regimen.

Exclusion Criteria

* Individuals with a history of other neuropathies due to causes other than diabetes such as alcohol abuse, liver or renal disease, uremia, toxic exposure, genetic factors, autoimmune disorders, inflammatory demyelinating diseases, monoclonal gammopathies; or endocrine, metabolic or nutritional disorders.
* Has clinical or electrophysiologic evidence of bilateral carpal tunnel syndrome.
* Has a significant skin abnormality or ulcerative changes in their lower extremities that may interfere with the performance of the study related procedures.
* Has a body mass index greater than 45 kg/m2.
* Participants with uncontrolled hypertension or a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure of greater than 95 mm Hg.
* Has a history of myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, clinically significant abnormal electrocardiograms, New York Heart Association Functional Classification III or IV, or documented cerebrovascular accident.
* Has a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval greater than 450 milliseconds).
* Has a history of additional risk factors for Torsades de pointes.
* Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Medications that prolong the QT/QTc interval.
  * Lipoic acid.
  * Linolenic acid (primrose oil).
  * Inositol.
  * Topiramate.
  * Acetyl-L-Carnitine.
  * Nerve growth factors.
  * Capsaicin.
  * CYP3A4 inhibitors (amiodarone, diltiazem, Verapamil)
  * HIV protease inhibitors
  * Itraconazole
  * Ketoconazole
  * macrolide antibiotics
  * CYP 3A4 inducers
* Has an alanine aminotransferase level of greater than 1.5 times upper limit of normal, active liver disease or jaundice or Total bilirubin greater than 1.2 times upper limit of normal.
* Has a 12-hour urinary cortisol test greater than 264 nmol/night (95.6 mcg/night) at screening.
* Has clinically significant (as determined by the investigator) or unstable: pulmonary, gastrointestinal, hepatic, hematologic, musculoskeletal, osteoporosis, osteopenia, or endocrine (other than diabetes mellitus or stably treated hypothyroidism) diseases.
* Has a previous history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.
* Has any other serious disease or condition at screening or at randomization that might affect life expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.
* Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
* Has a known hypersensitivity to a compound related to TAK-583.
* Is currently participating in another investigational study or has participated in an investigational study within the past 30 days.

Primary outcomes:
measure: Change from Baseline for a composite measure of Maximal Nerve Conduction Velocity of the Peroneal and Median Motor Nerves and the Median and Sural Sensory Nerves.
timeFrame: Month 6 or Final Visit
Secondary outcomes:
measure: Change from Baseline in Electrophysiological Parameters for Individual Nerves.
timeFrame: Month 6 or Final Visit
measure: Change from Baseline in Sensory Sub-Composite and Motor Sub-Composite Scores.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in Vibration Perception Threshold.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in Pain Scores.
timeFrame: Months 1, 2, 3, 4, 5, and 6 or Final Visit
measure: Change in Neurological Examination Score.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in Quality of Life Index Score.
timeFrame: Months 1, 2, 3, 4, 5, and 6 or Final Visit
measure: Change in glycosylated hemoglobin.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in fasting plasma glucose.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in fasting insulin.
timeFrame: Months 3 and 6 or Final Visit
measure: Change in Fasting C-peptide.
timeFrame: Months 3 and 6 or Final Visit
Other outcomes:
Locations:
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Jonesboro
country: United States
state: Arkansas
city: Huntington Beach
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Tustin
country: United States
state: California
city: Largo
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Palm Beach Gardens
country: United States
state: Florida
city: Sunrise
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Englewood
country: United States
state: New Jersey
city: Buffalo
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Greenville
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Vancouver
country: Canada
state: British Columbia
city: Kingston
country: Canada
state: Ontario
city: North Bay
country: Canada
state: Ontario
city: Laval
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
Study officials:
affiliation: Takeda
name: VP Clinical Science
role: STUDY_DIRECTOR
References: