Safety Study of TAK-128 in Subjects With Diabetic Peripheral Neuropathy
Primary Purpose
Diabetic Neuropathies
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
TAK-128
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Neuropathies focused on measuring Diabetic Mononeuropathy, Diabetic Neuralgia, Mononeuropathy, Diabetic, Neuralgia, Diabetic, Diabetic Polyneuropathy, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Has successfully completed protocol 01-04-TL-128-003.
- Female subjects of childbearing potential must be nonpregnant, nonlactating and on an acceptable form of contraception.
- Must be in good health at Enrollment, as determined by a physician at the Month 6 Visit of Protocol 01-04-TL-128-003 (ie, via medical history and physical examination).
- Has clinical laboratory evaluations within the normal reference range for the testing laboratory, unless the results are deemed not clinically significant by the investigator or sponsor, at the Month 6 Visit of Protocol 01-04-TL-128-003.
- Has a creatinine level less than or equal to 2 mg/dL or 176.8 umol/L.
- The subject is willing to follow an American Diabetes Association or similar recommended dietary regimen.
Exclusion Criteria:
- Has developed other neuropathies due to causes other than diabetes such as alcohol abuse liver or renal disease, uremia, toxic exposure, genetic factors, inflammatory demyelinating diseases, monoclonal gammopathies; or endocrine, metabolic or nutritional disorders (included treated or untreated pernicious anemia).
- Has a systolic blood pressure greater than 160 mm HG or diastolic blood pressure is greater than 95 mm HG.
- The subject has an alanine aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease, or jaundice.
- Has a significant, actively treated or unstable pulmonary, cardiovascular, gastrointestinal, hepatic, hematologic, musculoskeletal, or endocrine (other than diabetes mellitus or stably treated hypothyroidism) disease.
Cannot use any of the following prescription medications throughout the duration of the study, including:
- Lipoic acid.
- Linolenic acid (primrose oil).
- Inositol.
- Topiramate.
- Acetyl-L-Carnitine.
- Nerve growth factors.
- Capsaicin.
- Has any other serious disease or condition at the Month 6 Visit of Protocol 01-04-TL-128-003 or at the Baseline/Rollover Visit that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TAK-128 100 mg QD
Arm Description
Outcomes
Primary Outcome Measures
Treatment-emergent adverse events, vital signs and physical examination findings.
Clinical Laboratory Tests (Hematology, Chemistry and Urinalysis).
Electrocardiogram results.
Weight.
Secondary Outcome Measures
Change from Baseline in composite nerve conduction velocities (Electrophysiologic Studies).
Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies).
Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing).
Change from Baseline in neurological examination (Clinical Neurologic Examination).
Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire).
Change from Baseline in quality of life index as assessed by the Short-Form, 36-Item Health Survey.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00756041
Brief Title
Safety Study of TAK-128 in Subjects With Diabetic Peripheral Neuropathy
Official Title
An Open-Label, Multi-Center Study to Evaluate the Safety of Long-Term Administration of TAK-128 in Subjects With Mild to Moderate Diabetic Peripheral Neuropathy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Terminated
Why Stopped
Lack of Efficacy.
Study Start Date
September 2005 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
September 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the safety of TAK-128, once daily (QD), for treatment of diabetic peripheral neuropathy
Detailed Description
Polyneuropathy is a frequent complication of diabetes; it affects most individuals after prolonged hyperglycemia, and diabetic neuropathy is very common in the developed world. Chronic, insidious, distal sensorimotor polyneuropathy with autonomic impairment is the most typical form of diabetic neuropathy. Less common, but more florid presentations include autonomic symptoms or painful neuropathy. Although many patients have no or relatively few symptoms, the chronic polyneuropathy and autonomic dysfunction predispose to neurotrophic foot ulceration; consequently, diabetes is the leading cause of amputation today.
Diabetic neuropathy is a dying-back polyneuropathy with distal degeneration of the longest nerve fibers advancing in a centripetal direction. Multiple histopathological changes are observed, but progressive fiber loss is the hallmark of diabetic polyneuropathy. Other important features include endothelial cell basement membrane thickening, segmental demyelination and remyelination, and axonal atrophy. Similar pathological changes are observed in type 1 and type 2 diabetes. The severity of neuropathy as indicated by the stage of nerve fiber loss determines the clinical, electrophysiological, and quantitative sensory threshold features of this disorder. The functional measures of electrophysiological and quantitative sensory thresholds reflect the morphological changes and the clinical features.
Diabetic polyneuropathy is etiologically related to prolonged hyperglycemia with multiple consequences. Although strict glycemic control prevents neuropathy in type 1 patients if maintained for many years, similar interventions in those with type 2 diabetes mellitus are less successful. Type 2 patients may have neuropathy with considerable nerve fiber loss at the time of diagnosis because of unsuspected hyperglycemia in preceding years. Reversal of established neuropathy with strict glycemic control is not certain to occur, even if maintained for many years. Co-morbid disease often interferes with strict management of type 2 diabetes. Even among those with type 1 diabetes, a minority of patients are successful in maintaining prolonged euglycemia.
TAK-128 is a novel synthetic compound being developed as a treatment for diabetic neuropathy. Subjects participating in this study successfully completed Protocol 01-04-TL-128-003, and earlier study of TAK-128.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Neuropathies
Keywords
Diabetic Mononeuropathy, Diabetic Neuralgia, Mononeuropathy, Diabetic, Neuralgia, Diabetic, Diabetic Polyneuropathy, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
221 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAK-128 100 mg QD
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
TAK-128
Intervention Description
TAK-128 100 mg tablet, orally, once daily for up to 1 year.
Primary Outcome Measure Information:
Title
Treatment-emergent adverse events, vital signs and physical examination findings.
Time Frame
At each visit
Title
Clinical Laboratory Tests (Hematology, Chemistry and Urinalysis).
Time Frame
At each visit
Title
Electrocardiogram results.
Time Frame
At each visit
Title
Weight.
Time Frame
At each visit
Secondary Outcome Measure Information:
Title
Change from Baseline in composite nerve conduction velocities (Electrophysiologic Studies).
Time Frame
Months 6 and 12 or Final Visit
Title
Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies).
Time Frame
Months 6 and 12 or Final Visit
Title
Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing).
Time Frame
Month 3, 6, 9 and 12 or Final Visit
Title
Change from Baseline in neurological examination (Clinical Neurologic Examination).
Time Frame
Month 3, 6, 9 and 12 or Final Visit
Title
Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire).
Time Frame
Month 3, 6, 9 and 12 or Final Visit
Title
Change from Baseline in quality of life index as assessed by the Short-Form, 36-Item Health Survey.
Time Frame
Month 3, 6, 9 and 12 or Final Visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has successfully completed protocol 01-04-TL-128-003.
Female subjects of childbearing potential must be nonpregnant, nonlactating and on an acceptable form of contraception.
Must be in good health at Enrollment, as determined by a physician at the Month 6 Visit of Protocol 01-04-TL-128-003 (ie, via medical history and physical examination).
Has clinical laboratory evaluations within the normal reference range for the testing laboratory, unless the results are deemed not clinically significant by the investigator or sponsor, at the Month 6 Visit of Protocol 01-04-TL-128-003.
Has a creatinine level less than or equal to 2 mg/dL or 176.8 umol/L.
The subject is willing to follow an American Diabetes Association or similar recommended dietary regimen.
Exclusion Criteria:
Has developed other neuropathies due to causes other than diabetes such as alcohol abuse liver or renal disease, uremia, toxic exposure, genetic factors, inflammatory demyelinating diseases, monoclonal gammopathies; or endocrine, metabolic or nutritional disorders (included treated or untreated pernicious anemia).
Has a systolic blood pressure greater than 160 mm HG or diastolic blood pressure is greater than 95 mm HG.
The subject has an alanine aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease, or jaundice.
Has a significant, actively treated or unstable pulmonary, cardiovascular, gastrointestinal, hepatic, hematologic, musculoskeletal, or endocrine (other than diabetes mellitus or stably treated hypothyroidism) disease.
Cannot use any of the following prescription medications throughout the duration of the study, including:
Lipoic acid.
Linolenic acid (primrose oil).
Inositol.
Topiramate.
Acetyl-L-Carnitine.
Nerve growth factors.
Capsaicin.
Has any other serious disease or condition at the Month 6 Visit of Protocol 01-04-TL-128-003 or at the Baseline/Rollover Visit that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sr. Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Safety Study of TAK-128 in Subjects With Diabetic Peripheral Neuropathy
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