Safety Study of DA-9801 to Treat Diabetic Neuropathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Dong-A ST Co., Ltd.
Sponsor:
Information provided by (Responsible Party):
Dong-A ST Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01822925
First received: March 21, 2013
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

To evaluate the effectiveness of DA-9801 at 300mg, 600mg, 900mg and placebo, in reducing pain in subjects with diabetic neuropathic pain compared to their baseline values.


Condition Intervention Phase
Diabetic Neuropathy
Drug: DA-9801 300mg
Drug: DA-9801 600mg
Drug: DA-9801 900mg
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 II Randomized, Double-Blind, Parallel Group, Dose-Ranging, Placebo-Controlled Study to Assess the Safety And Effectiveness Of DA-9801 in the Treatment of Subjects With Diabetic Neuropathy

Resource links provided by NLM:


Further study details as provided by Dong-A ST Co., Ltd.:

Primary Outcome Measures:
  • The Primary efficacy outcome in this study is the reduction in clinic visit pain score over the 12- week treatment period compared to baseline as assessed by the Likert numerical rating scale (NRS) [ Time Frame: Assessed at Screening and then at each week for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent reduction in clinic visit pain score over the 12-week treatment period compared to baseline as assessed by the Likert numerical rating scale (NRS) [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Proportion of subjects with at least 30% improvement compared to baseline as assessed by the Likert numerical rating scale (NRS) at the clinic visit [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Difference in average weekly pain score during 24 hours between dose groups as assessed by daily diary [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Difference in average weekly most severe pain between dose groups as assessed by daily diary [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12), and at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: No ]
  • Difference in average weekly overnight pain score between dose groups as assessed by daily diary [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12), and at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: No ]
  • Difference in average weekly pain score compared to baseline as assessed by daily diary [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Difference in average weekly overnight pain score compared to baseline as assessed by daily diary [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Proportion of responders in Patient Global Impression of Improvement (PGI-I) [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Change in Clinical Global Impression (CGI) over the course of the study [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]
  • Average weekly rescue medication use [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Incidence of Adverse Events (AEs) [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12), and at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: Yes ]
  • Incidence of withdrawals due to AEs [ Time Frame: Assessed weekly for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12), and at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: Yes ]
  • Changes/shifts in laboratory values [ Time Frame: Plasma samples will be taken for analysis at Screening, Treatment Visit 5, Treatment Visit 12, and then again at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: Yes ]
  • Changes in vital signs [ Time Frame: Vitals signs will be assesed at Screening, at each week for 12 weeks during the treatment period (Treatment Visit 1 through Treatment Visit 12) and at the final visit at week 14 (2 weeks after the final treatment visit) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 128
Study Start Date: October 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DA-9801 300mg
DA-9801 will be administered in tablet form, 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
Drug: DA-9801 300mg
300 mg of DA-9801 in tablet form, to be taken 3 times daily for 12 weeks.
Experimental: DA-9801 600mg
DA-9801 will be administered in tablet form, 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
Drug: DA-9801 600mg
600 mg of DA-9801 in tablet form, to be taken 3 times daily for 12 weeks.
Experimental: DA-9801 900mg
DA-9801 will be administered in tablet form, 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
Drug: DA-9801 900mg
900 mg of DA-9801 in tablet form, to be taken 3 times daily for 12 weeks.
Placebo Comparator: Placebo
Placebo (same formulation as DA-9801 but without the active ingredients) will be administered in tablet form, 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this tablet for 12 weeks.
Drug: Placebo
Placebo, in tablet form, to be taken 3 times daily for 12 weeks. The placebo is the same formulation as DA-9801 except that it does not contain the active pharmaceutical ingredient.

Detailed Description:

This is a double-blind, randomized, parallel group, dose ranging, placebo-controlled study where eligible subjects (age 18 to 75 years) will have an average pain score ≥ 4 on an 11-point Likert numerical rating scale (NRS) for at least four days each week prior to randomization as assessed by daily pain diaries. Eligible subjects will be randomized to a 1:1:1:1 ratio to receive 300mg, 600mg, 900mg of DA-9801, or placebo three times a day for 12 weeks. During and at the end of the 12-week treatment period subjects will be evaluated for safety and efficacy parameters. A follow-up visit for safety will occur two weeks after the last treatment visit (TV).

The Screening Phase (2 weeks) is designed to determine whether subjects are eligible to proceed to the Treatment Phase of the study and consists of a series of screening assessments designed to determine eligibility. Eligible subjects will undergo a two-week washout period for medications and therapies administered for pain management.

At or up to 21 days before the Screening Visit, written informed consent from (ICF) the subject will be obtained by the Investigator or a suitably qualified designee before the performance of any protocol specific procedure. At the Screening Visit, the subject will be issued a daily diary in order to record daily pain level during the screening phase.

The Treatment Phase (TV0 to TV12) begins with a series of assessments designed to confirm the subjects' continued eligibility. The site will collect the daily diary and the subject's pain score will be determined. Only subjects whose average pain score is ≥ 4 for at least four days each week will be randomized to any of the four treatment groups.

DA-9801 administration schedule is three times per day, starting from TV0 to TV12.

During this study phase subjects will be evaluated on a weekly basis. Efficacy evaluations each week will include the subject's global impression of improvement and CGI of pain. Safety evaluations during the Treatment Phase will consist of adverse event assessments at each visit.

The Follow-up Visit (two weeks after last TV) The Follow-up Visit is designed to assess safety and will occur 14 days after the last TV. If the subject is withdrawn from the study prior to TV12, the subject should be exited from the study AFTER completing the specified assessments for that visit.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be 18 to 75 years of age
  • Diagnosed with Type I or Type II diabetes
  • HbA1c ≤ 12% at the time of screening
  • Has diabetic neuropathic pain (numbness, soreness, shooting or poking pain) in the lower extremities for more than 3 months prior to screening and with no adequate relief from other treatments
  • Has an average pain score of ≥ 4 for 24 hours at least 4 days out of the week prior to randomization as assessed by the 11-point Likert NRS.
  • If female of childbearing potential, subject must have a negative serum pregnancy test at screening
  • Understands and is willing to participate in the clinical study and can comply with study procedures and visits.
  • Normal cognitive and communicative ability as judged by clinical assessment and ability to complete self-reported questionnaires
  • Subject is willing and able to give informed consent

Exclusion Criteria:

  • Evidence of another type of neuropathic pain caused by a condition other than diabetes
  • Pain from another source as severe or greater than the pain under study
  • BMI (Body Mass Index) > 37 kg/m2
  • Clinical signs of infection related to sores of any type on the legs
  • Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding screening; or subject or physician anticipates use of any of these therapies by the subject during the course of the study
  • Previous participation in the Treatment Phase of this Protocol
  • History of drug or alcohol abuse, within the past 6 months
  • Malignant disease not in remission for 5 years or more that has been medically or surgically treated without evidence of metastases
  • Presence of one or more medical conditions, as determined by medical history, which seriously compromises the subject's ability to complete the study, including history of poor adherence with medical treatment, renal, hepatic, hematologic, active auto-immune or immune diseases that, in the opinion of the Investigator, would make the subject an inappropriate candidate for this study: c) One or more abnormal blood biochemistry analyte result that is ≥ 3 times that of the upper limit of the normal range; d) For laboratory results that are significantly lower than the normal range, specific criteria will be used to judge subject eligibility for randomization for Total protein, Albumin, and Hemoglobin or Platelets.
  • Known history of having Acquired Immunodeficiency Syndrome (AIDS) or with a history known to be infected with Human Immunodeficiency Virus (HIV)
  • New York Heart Association (NYHA) Class III and IV congestive heart failure (CHF), as defined by the following criteria: a)Class III: Symptoms with moderate exertion b)Class IV: Symptoms at rest
  • Pregnant or breast feeding
  • Women of child-bearing potential not using an effective birth control method. Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria:

    d) Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m, OR; e) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, OR; f) Are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods. Reliable contraception should be maintained throughout the study and for 7 days after study discontinuation.

  • Subjects with a diagnosis of psychiatric disorders such as major depressive disorder, bipolar disorder, obsessive compulsive disorder, generalized anxiety, dysthymia or suicidality/suicide ideation
  • Administration of local anesthetic shot or systemic steroids within two months of screening
  • Subjects not willing to undergo a two-week washout period for pharmacologic and non-pharmacologic pain management techniques
  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: NCT01822925

Contacts
Contact: Anand Balasubramanian 301-956-2531 anandb@amarexcro.com

Locations
United States, California
Center for United Research, Inc. Recruiting
Lakewood, California, United States, 90712
Principal Investigator: Gnyandev S Patel, MD         
Diablo Clinical Research Recruiting
Walnut Creek, California, United States, 94598-3347
Principal Investigator: Richard Weinstein, MD         
United States, Connecticut
Clinical Research Consulting, LLC Recruiting
Milford, Connecticut, United States, 06460
Principal Investigator: Susann Varano, MD         
United States, Florida
Metabolic Research Institute, Inc. Recruiting
West Palm Beach, Florida, United States, 33401
Principal Investigator: Barry M Horowitz, MD         
United States, Massachusetts
Novex Clinical Research, Inc. Recruiting
New Bedford, Massachusetts, United States, 02740
Principal Investigator: Mushtaque A Chachar, MD         
United States, South Carolina
Coastal Carolina Research Center Recruiting
Mt. Pleasant, South Carolina, United States, 29464
Principal Investigator: Cynthia Strout, MD         
United States, Texas
North Texas Endocrine Center Recruiting
Dallas, Texas, United States, 75231
Principal Investigator: Peter Bressler, MD         
KRK Research Recruiting
Dallas, Texas, United States, 75230
Principal Investigator: Gloria H Cha, MD         
Houston Foot & Ankle Care Recruiting
Houston, Texas, United States, 77074
Principal Investigator: Gabriel Maislos, DPM         
United States, Utah
Wasatch Clinical Research Recruiting
Salt Lake City, Utah, United States, 84107
Principal Investigator: Brian Rasmussen, MD         
United States, Washington
Rainier Clinical Research Center, Inc. Recruiting
Renton, Washington, United States, 98057
Principal Investigator: Allen M Sussman, MD         
Sponsors and Collaborators
Dong-A ST Co., Ltd.
Investigators
Principal Investigator: Gabriel Maislos, D.P.M Houston Foot & Ankle Care
  More Information

No publications provided

Responsible Party: Dong-A ST Co., Ltd.
ClinicalTrials.gov Identifier: NCT01822925     History of Changes
Other Study ID Numbers: DA9801-DN-001
Study First Received: March 21, 2013
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dong-A ST Co., Ltd.:
Diabetes
Pain
Neuropathy

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

ClinicalTrials.gov processed this record on July 31, 2014