Efficacy and Safety of TAK-583 in Subjects With Diabetic Peripheral Neuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00760955
First received: September 24, 2008
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Diabetic Neuropathies
Drug: TAK-583
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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. [ Time Frame: Month 6 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Electrophysiological Parameters for Individual Nerves. [ Time Frame: Month 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in Sensory Sub-Composite and Motor Sub-Composite Scores. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Vibration Perception Threshold. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Pain Scores. [ Time Frame: Months 1, 2, 3, 4, 5, and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Neurological Examination Score. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Quality of Life Index Score. [ Time Frame: Months 1, 2, 3, 4, 5, and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in glycosylated hemoglobin. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in fasting plasma glucose. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in fasting insulin. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]
  • Change in Fasting C-peptide. [ Time Frame: Months 3 and 6 or Final Visit ] [ Designated as safety issue: No ]

Enrollment: 338
Study Start Date: September 2006
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-583 5 mg QD Drug: TAK-583
TAK-583 5 mg, tablets, orally, once daily for up to 6 months.
Experimental: TAK-583 50 mg QD Drug: TAK-583
TAK-583 50 mg, tablets, orally, once daily for up to 6 months.
Experimental: TAK-583 100 mg QD Drug: TAK-583
TAK-583 100 mg, tablets, orally, once daily for up to 6 months.
Placebo Comparator: Placebo QD Drug: Placebo
TAK-583 placebo-matching tablets, orally, once daily for up to 6 months.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00760955

  Show 38 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Clinical Science Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00760955     History of Changes
Other Study ID Numbers: 01-06-TL-583-006, U1111-1129-7781
Study First Received: September 24, 2008
Last Updated: May 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Asymmetric Diabetic Proximal Motor Neuropathy
Diabetic Amyotrophy
Diabetic Autonomic Neuropathy
Diabetic Polyneuropathy
Neuralgia, Diabetic
Symmetric Diabetic Proximal Motor Neuropathy
Drug Therapy

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Demyelinating Diseases
Polyneuropathies
Nerve Compression Syndromes
Neurologic Manifestations
Neurotoxicity Syndromes
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Signs and Symptoms
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on April 16, 2014