Efficacy and Safety Study of TAK-128 in Treating Subjects With Diabetic Peripheral Neuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00229437
First received: September 27, 2005
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to determine the efficacy and safety of TAK-128, once daily (QD), in treating subjects with diabetic peripheral neuropathy.


Condition Intervention Phase
Diabetic Neuropathies
Drug: TAK-128
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 Three Doses of TAK-128 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 in composite measure of maximal nerve conduction velocity (Nerve Conduction Studies). [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies). [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing). [ Time Frame: Weeks 12, 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire). [ Time Frame: Weeks: 8, 12, 16, 20, 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in the neurological examination (Clinical Neurological Examination). [ Time Frame: Weeks 12, 24 or Final Visit ] [ Designated as safety issue: No ]
  • Change from Baseline in quality of life index (SF-36 Health Survey). [ Time Frame: Weeks: 8, 12, 16, 20, 24 or Final Visit ] [ Designated as safety issue: No ]

Enrollment: 343
Study Start Date: March 2005
Study Completion Date: May 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-128 5 mg QD Drug: TAK-128
TAK-128 5 mg, tablets, orally, once daily for up to 6 months.
Experimental: TAK-128 50 mg QD Drug: TAK-128
TAK-128 50 mg, tablets, orally, once daily for up to 6 months.
Experimental: TAK-128 100 mg QD Drug: TAK-128
TAK-128 100 mg, tablets, orally, once daily for up to 6 months.
Placebo Comparator: Placebo QD Drug: Placebo
TAK-128 placebo-matching tablets, orally, once daily for up to 6 months.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female subjects of childbearing potential must be nonpregnant, nonlactating and on an acceptable form of contraception.
  • The subject 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.
  • The subject has type 1 or 2 diabetes mellitus using World Health Organization Criteria.
  • The subject has mild to moderate peripheral neuropathy defined as:

    • Clinical neuropathy score greater than or equal to 2.5 on the Michigan Neuropathy Screening Instrument.
    • Confirmed abnormality of at least 2 nerve conduction study velocity parameters as defined by the Neurological Core Laboratory.
    • Sural sensory nerve potential amplitude greater than or equal to 1 microvolt.
  • The subject's glycosylated hemoglobin is less than or equal to 10%.
  • The subject is on stable diabetic therapy for at least 3 months prior to randomization.
  • The subject is on stable pain medication for at least 6 weeks prior to randomization, if applicable.
  • The subject's creatinine level is 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:

  • The subject has a history of 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).
  • The subject has clinical or electrophysiologic evidence of bilateral carpal tunnel syndrome.
  • The subject has a significant skin abnormality or ulcerative changes in their lower extremities.
  • The subject's body mass index is greater than 40 kg/m2.
  • The subject's systolic blood pressure is greater than 160 mm Hg or diastolic blood pressure is greater than 95 mm Hg.
  • The subject has a history of myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, significant electrocardiograms, or documented cerebrovascular accident within 6 months prior to Screening, or is New York Heart Association Functional Cardiac Classification III or IV.
  • The subject has an alanine aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease, or jaundice.
  • The subject has a significant, actively treated or unstable pulmonary, gastrointestinal, hepatic, hematologic, musculoskeletal, or endocrine (other than diabetes mellitus or stably treated hypothyroidism) disease.
  • The subject has a previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug.
  • The subject has taken lipoic acid, linolenic acid (primrose oil), inositol, topiramate, Acetyl-L-Carnitine, nerve growth factors, or capsaicin within 30 days prior to Screening.
  • The subject 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 subject according to the protocol.
  • The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
  • The subject has a known hypersensitivity to a compound related to TAK-128.
  • Subjects can not 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
  • The subject currently is participating in another investigational study or has participated in an investigational study within the past (30 days or 5 half lives, whichever is longer).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00229437

  Show 48 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00229437     History of Changes
Other Study ID Numbers: 01-04-TL-128-003, U1111-1128-5843
Study First Received: September 27, 2005
Last Updated: February 27, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Takeda:
Diabetic Mononeuropathy
Diabetic Neuralgia
Mononeuropathy, Diabetic
Neuralgia, Diabetic
Diabetic Polyneuropathy
Drug Therapy

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 23, 2014