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

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00229437

Collaborator

(none)

343

Enrollment

Locations

Arms

Duration (Months)

7.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Neuropathies	Drug: TAK-128 Drug: TAK-128 Drug: TAK-128 Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

343 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 Three Doses of TAK-128 in Subjects With Mild to Moderate Diabetic Peripheral Neuropathy

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

May 1, 2006

Actual Study Completion Date :

May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Change from Baseline in composite measure of maximal nerve conduction velocity (Nerve Conduction Studies). [Week 24 or Final Visit]

Secondary Outcome Measures

Change from Baseline in the electrophysiologic parameters for individual nerves, including amplitudes (Nerve Conduction Studies). [Week 24 or Final Visit]
Change from Baseline in vibration perception threshold measurements (Quantitative Sensory Testing). [Weeks 12, 24 or Final Visit]
Change from Baseline in pain scores (Short-Form McGill Pain Questionnaire). [Weeks: 8, 12, 16, 20, 24 or Final Visit]
Change from Baseline in the neurological examination (Clinical Neurological Examination). [Weeks 12, 24 or Final Visit]
Change from Baseline in quality of life index (SF-36 Health Survey). [Weeks: 8, 12, 16, 20, 24 or Final Visit]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	City	State	Country
1	Mesa	Arizona	United States
2	Peoria	Arizona	United States
3	Phoenix	Arizona	United States
4	Tucson	Arizona	United States
5	Little Rock	Arkansas	United States
6	Huntington Beach	California	United States
7	La Jolla	California	United States
8	Long Beach	California	United States
9	Los Angeles	California	United States
10	Northridge	California	United States
11	San Francisco	California	United States
12	Torrance	California	United States
13	Tustin	California	United States
14	Aventura	Florida	United States
15	Fort Myers	Florida	United States
16	Hialeah	Florida	United States
17	Miami	Florida	United States
18	Palm Beach Gardens	Florida	United States
19	Plant City	Florida	United States
20	Decatur	Georgia	United States
21	Chicago	Illinois	United States
22	Louisville	Kentucky	United States
23	New Orleans	Louisiana	United States
24	Boston	Massachusetts	United States
25	Ann Arbor	Michigan	United States
26	Flint	Michigan	United States
27	St. Louis	Missouri	United States
28	Las Vegas	Nevada	United States
29	Elizabeth	New Jersey	United States
30	New Brunswick	New Jersey	United States
31	Buffalo	New York	United States
32	Staten Island	New York	United States
33	Greenville	North Carolina	United States
34	Oklahoma City	Oklahoma	United States
35	Morrisville	Pennsylvania	United States
36	Dallas	Texas	United States
37	Houston	Texas	United States
38	San Antonio	Texas	United States
39	Norfolk	Virginia	United States
40	Tacoma	Washington	United States
41	Calgary	Alberta	Canada
42	Vancouver	British Columbia	Canada
43	Kingston	Ontario	Canada
44	North Bay	Ontario	Canada
45	Sarina	Ontario	Canada
46	Gatineau	Quebec	Canada
47	Laval	Quebec	Canada
48	Quebec		Canada