Induction, STabilization, Adherence, and Retention Trial (ISTART) - A Randomized, Non-inferiority, Multicenter Study to Assess Early Treatment Efficacy of OX219 Versus SUBOXONE Film and to Explore Switching Between Treatments
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Orexo AB
- 入组人数
- 759
- 主要终点
- Primary Endpoints of Retention in Treatment at Days 3 and 15
研究概览
简要总结
The purpose of this study was to assess retention in treatment after induction with buprenorphine/naloxone (BNX) sublingual tablets compared with generic buprenorphine and after stabilization with BNX sublingual tablets compared with BNX film. Secondary objectives included assessment of treatment effects on opioid withdrawal symptoms, opioid cravings, and safety.
详细描述
This prospective, randomized, multicenter, parallel-group, non-inferiority study was conducted at 43 centers in the United States from August 2013 to April 2014. A non-inferior design was used because both products contain the same active components, and it was considered unethical to include a placebo arm. The study comprised an induction phase of 2 days and a stabilization phase of 20 days, with study visits scheduled on Days 1, 2, 3, 4, 8, 15, and 22. Eligible opioid-dependent patients were randomly assigned within 14 days of screening to induction with either the BNX sublingual tablets or generic buprenorphine tablets for 2 days. On Day 3, patients initially allocated to buprenorphine were switched to BNX film, whereas those allocated to BNX sublingual tablets continued on the same treatment. On Day 15, patients receiving BNX film were switched to BNX sublingual tablets, and those on BNX sublingual tablets were switched to BNX film. At the final study visit on Day 22, patients were offered the option of continuing in an open-label follow-up study of BNX sublingual tablets.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male/female 18-65 years old
- •Able to read, comprehend & sign the informed consent form
- •Meet opioid dependence criteria in DSM-IV-TR the past 12 months
- •Have a buprenorphine-negative UDS &/or urine dipstick
- •Prepared to abstain from opioids other than the study drug & from other addictive drugs
- •Negative urine pregnancy test
- •Females of childbearing potential who use a reliable method of contraception. Females of non-childbearing potential; surgically sterile or post-menopausal as defined by being at least 50 years of age & having an absence of menses for at least 2 years
- •Clearance from the prescribing MD to be withdrawn from their prescribed opioids for subjects receiving opioids for pain
- •Lack of clinically significant abnormalities in health assessments performed at screening. Unclear cases should be approved by the medical monitor
- •At least mild withdrawal symptoms (COWS ≥9)
排除标准
- •Pregnant, lactating or planning to be pregnant during study
- •Unwilling/unable to comply with the requirements of the protocol (e.g., pending incarceration) are in a situation/condition that may interfere with participation in the study
- •Prescribed treatment with generic buprenorphine monotherapy within 90 days prior start of treatment
- •Daily dose of methadone over 30 mg during the past week or who received the last dose of methadone less than 30 hours prior to treatment
- •Participating in other clinical studies in which medications is delivered or who have used an investigational drug/device within the last 30 days
- •Allergy, sensitivity or intolerance to BUP, NAL or any related drug; history of drug hypersensitivity or intolerance which, in the opinion of the investigator, would compromise the safety of the subject/study
- •Staff, affiliated with, or family member of the staff directly involved with this study
- •Serious untreated Axis I DSM-IV-TR psychiatric comorbidity (actively suicidal or homicidal, have untreated schizophrenia)
- •Tongue/oral deformities that may affect the absorption of the drug products
- •Current/history of clinically significant medical disorder or condition which would jeopardize the safety or impact the validity of the results. Unclear cases should be discussed with & approved by the medical monitor
- •HIV-seropositive with a CD4+ count <200, active AIDS defining infection in the last 120 days
- •Have Class III/IV congestive heart failure, symptomatic myocardial ischemia or history of long QT syndrome (or an immediate family member with this condition)
- •Currently taking Class 1A antiarrhythmic medications (e.g., quinidine, procainamide, & disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, & dofetilide)
- •Have uncontrolled hypertension, pulse oximetry ≤92%or clinically significant abnormality on 12-lead ECG, including a corrected QT (QTc) interval >450 ms
- •Severe liver disease
研究组 & 干预措施
Buprenorphine; then OL BNX film, then BNX tablets
Days 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets
干预措施: BNX sublingual tablets (Drug)
Buprenorphine; then OL BNX film, then BNX tablets
Days 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets
干预措施: BNX sublingual film (Drug)
Buprenorphine; then OL BNX film, then BNX tablets
Days 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets
干预措施: Buprenorphine (Drug)
BNX tablets, then OL BNX tablets, then BNX film
Days 1-2: BNX sublingual tablets (blinded); Days 3 to 14: BNX sublingual tablets (open-label); Days 15-21: Buprenorphine/naloxone sublingual film (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets
干预措施: BNX sublingual tablets (Drug)
BNX tablets, then OL BNX tablets, then BNX film
Days 1-2: BNX sublingual tablets (blinded); Days 3 to 14: BNX sublingual tablets (open-label); Days 15-21: Buprenorphine/naloxone sublingual film (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets
干预措施: BNX sublingual film (Drug)
结局指标
主要结局
Primary Endpoints of Retention in Treatment at Days 3 and 15
时间窗: Day 3 and Day 15
Retention rates (number of patients retained) for the primary efficacy endpoints of retention in treatment at Days 3 and 15, which was defined as the number of patients who received treatment on Days 3 and 15.
次要结局
- Clinical Opiate Withdrawal Scale (COWS) Scores: Induction(Days 1 and 2)
- COWS Total Scores: Stabilization/Maintenance(Days 3 through 22)
- Subjective Opiate Withdrawal Scale (SOWS) Scores: Induction(Days 1 and 2)
- Visual Analog Scale (VAS) Cravings: Induction(Days 1 and 2)
- VAS Craving Scores: Stabilization/Maintenance(Days 3 through 22)
- SOWS Total Scores: Stabilization/Maintenance(Days 3 through 22)