A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 391
- 试验地点
- 65
- 主要终点
- Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
研究概览
简要总结
The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.
详细描述
The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks.
Participants entered the open label titration period and received hydrocodone ER tablets beginning with 15 mg every 12 hours for 3 to 7 days. The objective of the open label titration period was to find the successful dose of hydrocodone ER tablets that produced stable pain relief (defined as an Average Pain Intensity (API) score of 4 or less on the 11-point numerical rating scale for either 3 consecutive days or 3 out of 5 consecutive days while the patient was maintained on the same dose of study drug for up to 7 days). Patients returned to the study center prior to each dose adjustment.
Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Patients began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
- •The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
- •Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
- •The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
- •The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the 11-point numerical rating scale.
- •If the patient is receiving physical therapy, biofeedback therapy, acupuncture therapy, or herbal remedies, these therapies must remain unchanged during the study.
- •The patient must not participate in other study involving an investigational agent while enrolled into the present study.
排除标准
- •The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
- •The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
- •The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
- •The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
- •The patient has a history of suicidality.
- •The patient is expected to have surgery during the study.
- •The patient's primary painful condition under study is related to any source of chronic pain other than osteoarthritis or low back pain.
- •The patient is pregnant or lactating.
- •The patient has active malignancy.
- •The patient has human immunodeficiency virus (HIV).
- •In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination and/or clinical laboratory test values.
- •The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
- •The patient has participated in a study involving an investigational drug in the previous 30 days.
- •The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
- •The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that would, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.
- •The patient is involved in active litigation in regard to the pain currently being treated.
- •The patient has a positive urine drug screen (UDS) that is not medically explainable.
- •The investigator feels that the patient is not suitable for the study for any reason.
研究组 & 干预措施
Placebo
Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.
干预措施: Hydrocodone ER (Drug)
Placebo
Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.
干预措施: Placebo (Drug)
Hydrocodone ER
Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets every 12 hours at the dosage deemed successful for managing their pain during the titration period.
干预措施: Hydrocodone ER (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
时间窗: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period
The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.
次要结局
- Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period)
- Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period)
- Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period)
- Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period)
- Clinician Assessment of Patient Function (CAPF) at Week 4(Week 4 of the Double-blind Treatment Period)
- Clinician Assessment of Patient Function (CAPF) at Week 8(Week 8 of the Double-blind Treatment Period)
- Clinician Assessment of Patient Function (CAPF) at Week 12(Week 12 of the Double-blind Treatment Period)
- Clinician Assessment of Patient Function (CAPF) at Endpoint(Endpoint of the Double-blind Treatment Period (up to week 12))
- Patient Assessment of Function (PAF) at Week 4(Week 4 of the Double-blind Treatment Period)
- Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason(Day 1 to Week 12 of the double-blind treatment period)
- Kaplan-Meier Estimates for Time to Discontinuation From the Study(Day 1 to Week 12 of the double-blind treatment period)
- Patient Assessment of Function (PAF) at Week 8(Week 8 of the Double-blind Treatment Period)
- Patient Assessment of Function (PAF) at Week 12(Week 12 of the Double-blind Treatment Period)
- Patient Assessment of Function (PAF) at Endpoint(Endpoint of the Double-blind Treatment Period (up to week 12))
- Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period)
- Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint(Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period)
- Brief Pain Inventory - Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period)
- Participants With Adverse Events(Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period)
- Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period(Day 1 up to Day 128 in Double-Blind Treatment period)
- Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period(Day 1 up to Day 128 in Double-Blind Treatment period)
- Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period(Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period)
- Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period(Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period)
- Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods(Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period)
- Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods(Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period)
- Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters(Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period)