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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00760955
Recruitment Status : Completed
First Posted : September 26, 2008
Last Update Posted : June 22, 2016
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Diabetic Neuropathies Drug: TAK-583 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 338 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2006
Actual Primary Completion Date : February 2008
Actual Study Completion Date : February 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Change from Baseline in Electrophysiological Parameters for Individual Nerves. [ Time Frame: Month 6 or Final Visit ]
  2. Change from Baseline in Sensory Sub-Composite and Motor Sub-Composite Scores. [ Time Frame: Months 3 and 6 or Final Visit ]
  3. Change in Vibration Perception Threshold. [ Time Frame: Months 3 and 6 or Final Visit ]
  4. Change in Pain Scores. [ Time Frame: Months 1, 2, 3, 4, 5, and 6 or Final Visit ]
  5. Change in Neurological Examination Score. [ Time Frame: Months 3 and 6 or Final Visit ]
  6. Change in Quality of Life Index Score. [ Time Frame: Months 1, 2, 3, 4, 5, and 6 or Final Visit ]
  7. Change in glycosylated hemoglobin. [ Time Frame: Months 3 and 6 or Final Visit ]
  8. Change in fasting plasma glucose. [ Time Frame: Months 3 and 6 or Final Visit ]
  9. Change in fasting insulin. [ Time Frame: Months 3 and 6 or Final Visit ]
  10. Change in Fasting C-peptide. [ Time Frame: Months 3 and 6 or Final Visit ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00760955

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Sponsors and Collaborators
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Study Director: VP Clinical Science Takeda

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Responsible Party: Takeda Identifier: NCT00760955     History of Changes
Other Study ID Numbers: 01-06-TL-583-006
U1111-1129-7781 ( Registry Identifier: WHO )
First Posted: September 26, 2008    Key Record Dates
Last Update Posted: June 22, 2016
Last Verified: June 2016
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:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases