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

Primary Purpose

Diabetic Neuropathies

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TAK-128
TAK-128
TAK-128
Placebo
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

TAK-128 5 mg QD

TAK-128 50 mg QD

TAK-128 100 mg QD

Placebo QD

Arm Description

Outcomes

Primary Outcome Measures

Change from Baseline in composite measure of maximal nerve conduction velocity (Nerve Conduction Studies).

Secondary Outcome Measures

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 pain scores (Short-Form McGill Pain Questionnaire).
Change from Baseline in the neurological examination (Clinical Neurological Examination).
Change from Baseline in quality of life index (SF-36 Health Survey).

Full Information

First Posted
September 27, 2005
Last Updated
February 27, 2012
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT00229437
Brief Title
Efficacy and Safety Study of TAK-128 in Treating Subjects With Diabetic Peripheral Neuropathy
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
May 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 efficacy and safety of TAK-128, once daily (QD), in treating subjects with 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.

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
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
343 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TAK-128 5 mg QD
Arm Type
Experimental
Arm Title
TAK-128 50 mg QD
Arm Type
Experimental
Arm Title
TAK-128 100 mg QD
Arm Type
Experimental
Arm Title
Placebo QD
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
TAK-128
Intervention Description
TAK-128 5 mg, tablets, orally, once daily for up to 6 months.
Intervention Type
Drug
Intervention Name(s)
TAK-128
Intervention Description
TAK-128 50 mg, tablets, orally, once daily for up to 6 months.
Intervention Type
Drug
Intervention Name(s)
TAK-128
Intervention Description
TAK-128 100 mg, tablets, orally, once daily for up to 6 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
TAK-128 placebo-matching tablets, orally, once daily for up to 6 months.
Primary Outcome Measure Information:
Title
Change from Baseline in composite measure of maximal nerve conduction velocity (Nerve Conduction Studies).
Time Frame
Week 24 or Final Visit
Secondary Outcome Measure Information:
Title
Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies).
Time Frame
Week 24 or Final Visit
Title
Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing).
Time Frame
Weeks 12, 24 or Final Visit
Title
Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire).
Time Frame
Weeks: 8, 12, 16, 20, 24 or Final Visit
Title
Change from Baseline in the neurological examination (Clinical Neurological Examination).
Time Frame
Weeks 12, 24 or Final Visit
Title
Change from Baseline in quality of life index (SF-36 Health Survey).
Time Frame
Weeks: 8, 12, 16, 20, 24 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: 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Mesa
State/Province
Arizona
Country
United States
City
Peoria
State/Province
Arizona
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Huntington Beach
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Long Beach
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Northridge
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Torrance
State/Province
California
Country
United States
City
Tustin
State/Province
California
Country
United States
City
Aventura
State/Province
Florida
Country
United States
City
Fort Myers
State/Province
Florida
Country
United States
City
Hialeah
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Palm Beach Gardens
State/Province
Florida
Country
United States
City
Plant City
State/Province
Florida
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Flint
State/Province
Michigan
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Las Vegas
State/Province
Nevada
Country
United States
City
Elizabeth
State/Province
New Jersey
Country
United States
City
New Brunswick
State/Province
New Jersey
Country
United States
City
Buffalo
State/Province
New York
Country
United States
City
Staten Island
State/Province
New York
Country
United States
City
Greenville
State/Province
North Carolina
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Morrisville
State/Province
Pennsylvania
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Tacoma
State/Province
Washington
Country
United States
City
Calgary
State/Province
Alberta
Country
Canada
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Kingston
State/Province
Ontario
Country
Canada
City
North Bay
State/Province
Ontario
Country
Canada
City
Sarina
State/Province
Ontario
Country
Canada
City
Gatineau
State/Province
Quebec
Country
Canada
City
Laval
State/Province
Quebec
Country
Canada
City
Quebec
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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