A Phase 2 Study to Evaluate the Safety and Efficacy of RTA 901 in Patients With Diabetic Peripheral Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 209
- 试验地点
- 68
- 主要终点
- Change From Baseline in Weekly Average Pain Intensity Assessed by the Numeric Pain Rating Scale (NPRS) at Week 12
研究概览
简要总结
This is a 2-part, randomized, placebo-controlled, double-blind, Phase 2 study to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of RTA 901 in qualified participants with Diabetic Peripheral Neuropathic Pain (DPNP). Each study part will be randomized into 3 treatment arms; 2 different doses of RTA 901 and RTA 901-maching placebo. The doses of RTA 901 in Part 2 will be selected based on the Exposure-Response (E-R) analyses of data from Part 1.
The duration of each part of the study will be approximately 20 weeks, including a Screening period of up to 2 weeks, a Run-in-period of 2 weeks, a Treatment period of 12 weeks, and a Follow-up period of 4 weeks. All participants in Part 1 and Part 2 of the study will follow the same visit and assessment schedule. Eligibility will be assessed during the Screening and Run-in-periods.
详细描述
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) at least 1 year prior to Screening
- •Clinical diagnosis of DPNP defined as symptomatic distal symmetric polyneuropathy (secondary to diabetes) in the lower extremities, which may include symptoms of pain that is burning, lancinating, tingling, or shooting (electric shock-like). Pain in the lower extremities may occur with paresthesia or dysesthesia (unpleasant sensations of burning). Neuropathic pain may be accompanied by an exaggerated response to painful stimuli (hyperalgesia) and pain evoked by light touch or contact, eg, with socks, shoes, and bedclothes (allodynia);
- •NPRS pain intensity score ≥ 4 on an 11-point scale at Screening
- •A score ≥ 2.5 on the Michigan Neuropathy Screening Instrument (MNSI) Part B
排除标准
- •Has neuropathy from a cause other than T1DM or T2DM
- •Has a condition other than DPNP that could confound the assessment of pain (eg, fibromyalgia or regional pain caused by lumbar or cervical compression);
- •Diabetic foot ulceration or infection within 90 days prior to Screening
- •Prior participation in a study with RTA 901;
- •NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 1 RTA 901 Dose 1
Participants will receive study drug, once daily (QD), during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.
干预措施: RTA 901 (Drug)
Part 1 RTA 901 Dose 2
Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.
干预措施: RTA 901 (Drug)
Part 1 RTA 901-Matching Placebo
Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901-matching placebo, QD, for a 12-week treatment duration.
干预措施: RTA 901-Matching Placebo (Drug)
Part 2 RTA 901 Dose 1
Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.
干预措施: RTA 901 (Drug)
Part 2 RTA 901 Dose 2
Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.
干预措施: RTA 901 (Drug)
Part 2 RTA 901-Matching Placebo
Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901-matching placebo, QD, for a 12-week treatment duration.
干预措施: RTA 901-Matching Placebo (Drug)
结局指标
主要结局
Change From Baseline in Weekly Average Pain Intensity Assessed by the Numeric Pain Rating Scale (NPRS) at Week 12
时间窗: Baseline, Week 12
The NPRS of pain intensity is an 11-point numeric scale, ranging from 0 (representing no pain at all) to 10 (representing the worst pain imaginable). The participants were asked to select a whole number (0 to 10) that best indicates the intensity of his/her neuropathic pain in the past 24 hours. The weekly average score of NPRS was defined as the sum of non-missing daily scores divided by the number of days with non-missing scores for that week. Negative change from baseline indicates decreased pain intensity.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) During and Following the Treatment Period
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
An adverse event (AE) was any unfavorable and unintended sign (including any CS abnormal laboratory test result), symptom, or disease temporally associated with use of the study drug, whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of Investigator, placed participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AEs that presented, or worsened in intensity or frequency, following the initiation of study treatment were categorized as TEAEs.
Number of Participants With Clinically Significant Abnormalities in Physical Examinations
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Clinically significant abnormalities in physical examinations were based on investigator discretion.
Number of Participants With Potential Clinically Significant Abnormalities in Vital Sign Parameters
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Vital sign parameters included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36.0 and \> 38.0 degrees Celsius (c), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure \< 90, \> 140 and \> 160 millimeters of mercury (mmHg), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute. The categories with at least one participant with clinically significant vital sign abnormalities are reported.
Number of Participants With Shift From Baseline in Clinically Significant Abnormalities in Electrocardiogram (ECG)
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Clinical significance of abnormalities in ECG was determined based on the investigator's discretion.
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Hematology Parameters)
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Hematology parameters included hematocrit, hemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Blood Chemistry Parameters)
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Parameters included alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, choriogonadotropin beta, follicle stimulating hormone (FSH), estimated glomerular filtration rate (eGFR), ferritin, creatine kinase, blood urea nitrogen, creatinine, bilirubin(total and direct), alkaline phosphatase, amylase, lipase, sodium, potassium, calcium, phosphorus, uric acid, total protein, glucose, albumin, lactate dehydrogenase, magnesium, chloride, bicarbonate, and gamma-glutamyl transferase. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Urinalysis)
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Urinalysis included assessments of bacteria, Bilirubin, Calcium Oxalate Crystals, Choriogonadotropin Beta, Color, Erythrocytes, Glucose, Granular Casts, Hyaline Casts, Ketones, Leukocyte Esterase, Leukocytes, Nitrite, Occult Blood, Protein, red blood cells (RBC) Casts, Renal Epithelial Cells, Specific Gravity, Specimen Appearance, Squamous Epithelial Cells, Transitional Epithelial Cells, Triple Phosphate Crystals, Uric Acid Crystals, white blood cells (WBC) Casts and pH. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Coagulation Parameters)
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Coagulation included assessments of prothrombin. The parameter was flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline.
Number of Participants With Clinically Significant Abnormality in Body Weight
时间窗: From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Weight decrease was characterized by a decrease of ≥7% from baseline and weight increase was characterized by an increase of ≥7% from baseline.
次要结局
- Number of Participants Who Achieved at Least a >=30% Decrease From Baseline in the Average NPRS Score at Week 12(Baseline, Week 12)
- Number of Participants Who Achieved at Least a >=50% Decrease From Baseline in the Average NPRS Score at Week 12(Baseline, Week 12)
- Number of Participants Using Rescue Medications During the Treatment Period(Up to Week 12)
- Amount of Rescue Medications Used During the Treatment Period(Up to Week 12)
- Time to First Occurrence of Rescue Medication Use(Up to Week 12)
- Change From Baseline in the Weekly Average of Daily Sleep Interference Scale (DSIS) Score at Week 12(Baseline, Week 12)