CSP #1024 - A Phase III, Randomized, Multi-Center, Double Blind, Placebo-Controlled Study of Safety and Efficacy of Lofexidine for Relief of Symptoms in Subjects Undergoing Inpatient Opiate Detoxification.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 264
- 试验地点
- 16
- 主要终点
- SOWS-Gossop score on Day 3 during the treatment phase & time-to-dropout for the subjects in the two treatment groups. during the treatment phase.
研究概览
简要总结
The main objective of this study is to investigate the effectiveness of lofexidine in reducing withdrawal symptoms among subjects undergoing opiate detoxification. Currently, lofexidine is the most commonly used non-opiate medication for detoxification from opiates in the United Kingdom (UK). There is no non-opiate medication approved by the Food and Drug Administration (FDA) for the same indication in the United States (US). The only medications currently approved by the FDA for opiate detoxification are methadone and buprenorphine. These medications, however, have the potential to be abused. Lofexidine, on the other hand, offers a unique advantage for opiate detoxification because it is not addicting, is easy to use, and has a favorable safety profile.
详细描述
Primary Objective: The primary objective of this study is to investigate the efficacy of lofexidine hydrochloride, an alpha-2-adrenergic agonist, in reducing withdrawal symptoms in subjects undergoing opioid detoxification as assessed by 1)Day 3 SOWS-Gossop score during treatment phase, and 2)Time to dropout during treatment phase.
Secondary Objectives: Secondary objectives include determining Lofexidine's: 1) Efficacy in the reduction in withdrawal symptoms in subjects undergoing opioid detoxification (assessed by longitudinal changes in SOWS-Gossop, OOWS-Handelsman, VAS-E and MGCI (subject and rater); 2)Efficacy in the reduction in the need of any concomitant medication to alleviate opiate withdrawal symptoms: 3) Efficacy in increasing the number of completers during the treatment phase; and 4) Safety in the study population.
Study Design: This is a randomized, multi-center, double blind, placebo-controlled, parallel-group study. There are 3 major phases of the study. During Phase I (Screening) screening assessments will be performed; during Phase II (Days 1-5), subjects will be admitted to an inpatient unit and randomized to receive either lofexidine (0.8 mg QID) or placebo QID after the baseline assessments are performed prior to randomization on Day 1; and during Phase III (Days 6-8), all subjects will receive placebo QID on Days 6-7, and then be discharged on Day 8 following the post-treatment assessments. An adaptive randomization procedure will be used to randomly allocate subjects in one of the two treatment groups - lofexidine or placebo.
Study Population: 264 subjects with Diagnostic and Statistical Manual for Mental Disorders Fourth Edition (DSM-IV) criteria for current dependence on any opioid with a half-life similar to heroin or morphine determined by structured clinical interview (SCID) will be randomized in one of the treatment groups (132 subjects per group). Subjects at least 18 years-of-age with positive urine toxicology screen for opiates and negative for methadone, LAM/LAAM, or buprenorphine during screening, with the ability to understand and provide written informed consent that meet all the inclusion criteria and do not meet any of the exclusion criteria may be randomized into the study.
Treatments: On Day 1, subjects are randomized to either lofexidine or placebo and receive lofexidine (0.8 mg [4 x 0.2 mg lofexidine tablets] QID) or placebo (4 matching placebo tablets QID). Lofexidine or placebo will be administered orally within 15 minutes before or after 0800, 1300, 1800 and 2300 hours on Days 1-5. On Days 6 and 7, all subjects will receive placebo using the same dosing schedule as above.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Potential subjects must:
- •Be at least 18 years of age.
- •Have current dependence, according to SCID criteria, on any opioid with a half-life similar to heroin or morphine, including Vicodin, Lortab, or Lorcet, Percocet, Percodan, Tylox, or Hydrocodone (by any route of administration), or oxycodone (oxycodone and oxycodone time-released formulation when crushed and snorted, injected or swallowed after chewing).
- •Be seeking treatment for opiate dependence.
- •Have a score greater than or equal to 2 on the Objective Opiate Withdrawal Scale-Handelsman (OOWS) immediately prior to admission.
- •Have reported use of heroin, morphine, or any opioid with a half-life similar to heroin or morphine, for at least 21 of the past 30 days.
- •Have urine toxicology screen positive for opiates and negative for methadone or buprenorphine.
- •If female and of child bearing potential, agree to use of one of the following methods of birth control:
- •oral contraceptives
- •barrier (diaphragm, sponge or condom) plus spermicidal preparations
- •intrauterine contraceptive system
- •levonorgestrel implant
- •medroxyprogesterone acetate contraceptive injection
- •complete abstinence from sexual intercourse
- •hormonal vaginal contraceptive ring
- •surgical sterilization or partner sterile (must have documented proof)
- •Have completed the ASI during screening and all other assessments (SOWS-Gossop OOWS, and MCGI) during the baseline period.
- •Be able to verbalize understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures and pass the study consent quiz with 100% accuracy (if necessary, quiz may be administered more than one time).
排除标准
- •Potential subjects must not:
- •Be female subjects who are pregnant or lactating.
- •Have self-reported use of methadone or buprenorphine in the past 14 days.
- •Have serious medical illnesses including, but not limited to:
- •Seizures, or those who have received anticonvulsant therapy during the past 5 years.
- •Pancreatic disease such as insulin-dependent diabetes.
- •Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 5 times the upper limit of normal.
- •Gastrointestinal or renal disease, which would significantly impair absorption, metabolism or excretion of study drug, or would require medication or medical treatment.
- •Have a psychiatric disorder, as assessed by the SCID, including but not limited to dementia or any disorder that, in the opinion of the study physician requires ongoing treatment that would make study participation unsafe or which would make treatment compliance difficult.
- •Have self-reported AIDS.
- •Have an abnormal cardiovascular exam prior to randomization, including any of the following:
- •Clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, or QTc interval > 450 msec for males, and > 470 msec for females).
- •Heart rate less than 45 bpm or symptomatic bradycardia.
- •Systolic blood pressure < 90 mm Hg or symptomatic hypotension (diastolic blood pressure < 60 mm Hg).
- •Blood pressure > 160/100 mm Hg.
- •Prior history of myocardial infarction.
- •Have clinically significant abnormal laboratory values.
- •Require any of the following medications currently or within the past 4 weeks: psychotropics (including sedatives/hypnotics, antidepressants, neuroleptics), prescription analgesics (excluding those listed in inclusion criteria #2 above), anticonvulsants, antihypertensives, antiarrhythmics, antiretroviral, and cholesterol lowering medications. Nicotine replacement therapy (patch, inhaler, gum, or nasal spray) for nicotine-dependent subjects are allowed.
- •Have current dependence (by SCID criteria) on
研究组 & 干预措施
1
Lofexidine 0.8 mg QID
干预措施: Lofexidine (Drug)
2
Placebo QID
干预措施: Placebo (Drug)
结局指标
主要结局
SOWS-Gossop score on Day 3 during the treatment phase & time-to-dropout for the subjects in the two treatment groups. during the treatment phase.
时间窗: Day 3 of treatment phase for the SOWs score. Time to dropout will be measured as the number of 6-hour time quadrants until a subject withdraws or completes the treatment phase of the study
次要结局
未报告次要终点