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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 14
- 主要终点
- Change in Clinic Visit Pain Score at the 12 Week Visit Compared to Baseline as Assessed by the 11-point Likert Numerical Rating Scale (NRS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
DA-9801 300mg
DA-9801 will be administered in tablet form, 100mg taken 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
干预措施: DA-9801 300mg (Drug)
DA-9801 600mg
DA-9801 will be administered in tablet form, 200 mg taken 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
干预措施: DA-9801 600mg (Drug)
DA-9801 900mg
DA-9801 will be administered in tablet form, 300 mg taken 3 times daily to subjects randomized to this arm of the study. Subjects will be expected to take this medication for 12 weeks.
干预措施: DA-9801 900mg (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Clinic Visit Pain Score at the 12 Week Visit Compared to Baseline as Assessed by the 11-point Likert Numerical Rating Scale (NRS)
时间窗: Baseline to 12 weeks of treatment
Pain score was assessed by the subject using the 11-point Likert rating scale for pain (0=no pain to 10=worst possible pain) prior to conduct of any other study assessment. The change in clinic visit pain score at the 12-week visit was compared to baseline.
次要结局
- Percentage Change in Clinic Visit Pain Score at the 12-week Visit Compared to Baseline as Assessed by the 11-point Likert Numerical Rating Scale (NRS)(Baseline and over 12 week treatment period)
- Number of Participants With at Least 30% Improvement Compared to Baseline as Assessed by the 11- Point Likert Numerical Rating Scale (NRS) at the Week 12 Clinic Visit(Baseline to 12 week treatment period)
- Difference in Average Weekly Pain Score Between Dose Groups as Assessed by Daily Diary(Baseline to 12 week treatment period)
- Difference in Average Weekly Most Severe Pain Score Between Dose Groups as Assessed by Daily Diary(Baseline to 12 week treatment period)
- Difference in Average Weekly Overnight Pain Score Between Dose Groups as Assessed by Daily Diary(Baseline to 12 week treatment period)
- Change From Baseline Within Group- Difference in Average Weekly Pain Score Compared to Baseline as Assessed by Daily Diary(Baseline to 12 week treatment period)
- Average Weekly Rescue Medication Use(Week 1 to Week 12)
- Change From Baseline Within Group-Difference in Average Weekly Overnight Pain Score Compared to Baseline as Assessed by Daily Diary(Baseline to 12 week treatment period)
- Number of Participants Considered to be Responders on Global Impression of Improvement (PGI-I) at Week 12(Week 12)
- Number of Participants Number of Participants Considered to be Responders in Clinical Global Impression (CGI) at Week 12(Week 12)