Safety Study of TAK-128 in Subjects With Diabetic Peripheral Neuropathy
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Treatment-emergent adverse events, vital signs and physical examination findings. [ Time Frame: At each visit ] [ Designated as safety issue: Yes ]
- Clinical Laboratory Tests (Hematology, Chemistry and Urinalysis). [ Time Frame: At each visit ] [ Designated as safety issue: Yes ]
- Electrocardiogram results. [ Time Frame: At each visit ] [ Designated as safety issue: Yes ]
- Weight. [ Time Frame: At each visit ] [ Designated as safety issue: Yes ]
- Change from Baseline in composite nerve conduction velocities (Electrophysiologic Studies). [ Time Frame: Months 6 and 12 or Final Visit ] [ Designated as safety issue: No ]
- Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies). [ Time Frame: Months 6 and 12 or Final Visit ] [ Designated as safety issue: No ]
- Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing). [ Time Frame: Month 3, 6, 9 and 12 or Final Visit ] [ Designated as safety issue: No ]
- Change from Baseline in neurological examination (Clinical Neurologic Examination). [ Time Frame: Month 3, 6, 9 and 12 or Final Visit ] [ Designated as safety issue: No ]
- Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire). [ Time Frame: Month 3, 6, 9 and 12 or Final Visit ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||September 2006|
|Primary Completion Date:||September 2006 (Final data collection date for primary outcome measure)|
|Experimental: TAK-128 100 mg QD||
TAK-128 100 mg tablet, orally, once daily for up to 1 year.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00756041
|Study Director:||Sr. Medical Director Clinical Science||Takeda|