Study PXN110527: The Investigation of the Efficacy and Pharmacokinetics of XP13512 in Subjects With Neuropathic Pain Associated With Post-herpetic Neuralgia (PHN) Who Have Had an Inadequate Response to Gabapentin Treatment.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using Last Observation Carried Forward (LOCF) Data
研究概览
简要总结
The purpose of this study is evaluate the difference between two doses of gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, on pain associated with post-herpetic neuralgia.
详细描述
The primary purpose of study PXN110527 was to investigate the efficacy of a high (3600mg/day) dose versus a low (1200mg/day) dose of GEn in subjects with post-herpetic neuralgia (PHN) who have a history of an inadequate response to gabapentin treatment. The study is a cross-over design. Prior to screening subjects are required to have a demonstrated history of an inadequate response (as determined by the investigator) to at least 1800 mg/day of gabapentin. Prior history of treatment with gabapentin includes current treatment at 1800mg/day (2 weeks) or prior treatment with ≥1800mg/day (4 weeks). Subjects could also have been treated with pregabalin monotherapy (150-300mg/day, ≥4 weeks) and had an inadequate response.
Subjects are treated with gabapentin 1800mg/day during the Baseline Period and are randomized if during the Basleline Period they are compliant with gabapentin treatment and have a 24-hour average pain intensity score ≥4.0 based on an 11-point pain intensity numerical rating scale (PI-NRS). Subjects are then randomized to receive gabapentin enacarbil (either 1200mg/day or 3600mg/day in a 1:1 ratio) for Treatment Period 1 (28 days). Followed by a dose of 2400mg/day for 4 days and the alternate fixed dose (either 3600 mg/day or 1200 mg/day) for Treatment Period 2 (28 days).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, 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
- •18 years or older
- •Documented medical diagnosis of PHN with pain present for at least 3 months from the healing of a herpes zoster rash
- •Female subjects are eligible if of non-childbearing potential or not lactating, has a negative pregnancy, and agrees to use one a specified highly effective method for avoiding pregnancy.
- •Currently on a stable dose of 1800 mg/day of gabapentin for ≥2 weeks with inadequate response OR
- •Not currently treated with gabapentin, but previously treated with ≥1800 mg/day of gabapentin for 4 weeks or more with inadequate response.
- •Baseline 24-hour average pain intensity score ≥ 4.0 based on an 11-point PI-NRS
- •Provides written informed consent in accordance with all applicable regulatory requirements
排除标准
- •Other chronic pain conditions not associated with PHN. However, the subject will not be excluded if:
- •The pain is located at a different region of the body; and
- •The pain intensity is not greater than the pain intensity of the PHN; and
- •The subject can assess PHN pain independently of other pain
- •Is unable to discontinue prohibited medications or non-drug therapies or procedures throughout the duration of the study
- •Hepatic impairment defined as ALT or AST > 2x upper limit of normal (ULN), or alkaline phosphatase or bilirubin > 1.5x ULN
- •Chronic hepatitis B or C
- •Impaired renal function defined as creatinine clearance <60 mL/min or requiring hemodialysis
- •Corrected QT (QTc) interval ≥ 450 msec or QTc interval ≥480 msec for patients with Bundle Branch Block
- •Uncontrolled hypertension at screen (sitting systolic >160 mmHg and/or sitting diastolic >90 mmHg)
- •Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drugs
- •Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GEn, or, in the investigator's judgment
- •Is considered to be clinically significant and may pose a safety concern, or,
- •Could interfere with the accurate assessment of safety or efficacy, or,
- •Could potentially affect a subject's safety or study outcome
- •Current or chronic history of liver disease (including acute viral hepatitis), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Meets criteria defined by the DSM-IV-TR for a major depressive episode or for active significant psychiatric disorders within last year
- •Depression in remission, with or without antidepressant treatment, may participate, unless stable antidepressant regimen is a prohibited medication
- •Antidepressant medication may not be changed or discontinued to meet entry criteria and must be stable for at least three months prior to enrollment
- •History of clinically significant drug or alcohol abuse (DSM-IV-TR) or is unable to refrain from substance abuse throughout the study. Benzodiazepines or atypical benzodiazepines as hypnotic sleep agents permitted.
- •Currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device
- •Has participated in a clinical study and was exposed to investigational or non-investigational drug or device:
- •Within preceding month for studies unrelated to PHN, or
- •Within preceding six months for studies related to PHN
- •Treated previously with GEn
- •History of allergic or medically significant adverse reaction to investigational products (including gabapentin) or their excipients, acetaminophen or related compounds
研究组 & 干预措施
GEn 1200mg/day
gabapentin enacarbil 1200mg/day, 4 weeks treatment in either the first or second treatment period
干预措施: GEn 1200mg/day (Drug)
GEn 3600mg/day
gabapentin enacarbil 3600mg/day, 4 weeks treatment in either the first or second treatment period
干预措施: GEn 3600mg/day (Drug)
结局指标
主要结局
Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using Last Observation Carried Forward (LOCF) Data
时间窗: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
Baseline and end of treatment values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (baseline) and the last 7 days on treatment within each period (end of treatment). Participants rated their API over the preceding 24 hours, using an 11-point PI-Numerical Rating Scale (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as end of treatment minus baseline. Data are summarized by dose, independent of treatment period.
Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data for Each Treatment Period
时间窗: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
Baseline and end of treatment values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (baseline) and the last 7 days on treatment within each period (end of treatment). Participants used a hand-held diary to rate their average pain intensity over the preceding 24 hours, using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. The by period summary is provided as a sensitivity analysis for the primary analysis.
次要结局
- Change From Baseline in the Mean Day-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Current (Evening) Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Night-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data by Period(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Current Morning Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at the Last Week of Each Treatment Period(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) at the Last Week of Each Treatment Period Using LOCF Data(End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data(End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Using LOCF Data(End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data(End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))
- Change From Baseline in the Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at the Last Week of Each Treatment Period Using LOCF(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of treatment))
- Mean Gabapentin Steady-State (ss) Average, Minimum and Maximum Concentrations(A total of 10 blood samples (2 samples at each visit) were collected per participant at Baseline, and the Week 1 and Week 4 visits for each period)
- Change From Baseline in the Mean Sleep Interference Score at the Last Week of Each Treatment Period Using LOCF Data(Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period))