A 12-Month, Open-Label Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours in Patients 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
- 330
- 试验地点
- 54
- 主要终点
- Participants With Clinically Significant (CS) Hearing Changes From Baseline in Pure Tone Audiometry Test Results by Patient Status
研究概览
简要总结
The primary objective of this study is to evaluate the safety of hydrocodone extended-release tablets when used over a 12-month period in patients with chronic pain, as assessed by adverse events, clinical laboratory results, vital signs measurements, electrocardiogram results, physical examination findings, pure tone audiometry, and concomitant medication usage.
详细描述
This was a Phase 3, open-label, nonrandomized study that consisted of a screening period, an open label titration period, and a 52 week, long term, open-label treatment period in patients with chronic pain. Patients were eligible to participate in this study if they had completed study C33237/3079 (NCT01240863) (these patients are hereafter referred to as rollover patients) or if they had not participated in study 3079 (these patients are hereafter referred to as either new opioid naïve or new opioid experienced patients).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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 must be willing and able to successfully self-administer the study drug, comply with study restrictions, and return to the clinic for scheduled study visits as specified in this protocol.
- •The patient has either completed Cephalon study 3079 or has chronic pain of at least 3 months duration prior to entering this study associated with any of the following conditions: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain, osteoarthritis, or rheumatoid arthritis. Patients with other painful conditions may qualify for the study with permission from the Cephalon medical monitor or designee.
- •Those patients who completed the 12-week, double-blind, placebo-controlled, randomized study (study 3079) and are willing to re-titrate study drug to an effective dose of hydrocodone extended-release tablets are eligible to enter this study.
- •The patient is able to speak English, willing to provide written informed consent, and sign a written opioid agreement, to participate in this study.
- •The patient is 18 through 80 years of age (inclusive) at the time of entering this or the previous study (study 3079).
- •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.
排除标准
- •Patients who were enrolled in study 3079 but did not complete the 12-week, double-blind, placebo-controlled, randomized study may not be enrolled into this study.
- •The patient has known or suspected hypersensitivities, allergies, or other contraindications to the study drug or its excipients.
- •The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse.
- •The patient has a medical or psychiatric condition/disease that, in the opinion of the investigator, would compromise collected data.
- •The patient is taking a total (i.e., including around-the clock [ATC] and rescue medications) of more than 135 mg/day of oxycodone or equivalent for 14 days prior to screening.
- •The patient has a history of suicidality.
- •The patient has a diagnosis of chronic headache or migraine as the primary painful condition under study.
- •The patient is expected to have surgery during the study and it is anticipated that the surgery will alleviate the patient's 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 potent synthetic opioids.
- •The patient has participated in a study involving an investigational drug in the previous 30 days (excluding those who participated in study 3079).
- •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 chronic pain currently being treated.
- •The patient has a positive urine drug screen (UDS) for an illicit substance or medication not prescribed by the physician currently treating the chronic pain.
- •The investigator feels that the patient is not suitable for the study.
研究组 & 干预措施
Hydrocodone ER
Participants were titrated (or re-titrated for roll-over participants) at escalating dosages of extended-release hydrocodone tablets at dosages of 15, 30, 45, 60, or 90 mg orally every 12 hours until deemed successful for managing their pain during the open-label titration period. Once a successful dose was identified, participants entered the 52 week open-label treatment period in which hydrocodone ER was administered at the successful dose (15, 30, 45, 60, or 90 mg) every 12 hours.
干预措施: Hydrocodone ER (Drug)
结局指标
主要结局
Participants With Clinically Significant (CS) Hearing Changes From Baseline in Pure Tone Audiometry Test Results by Patient Status
时间窗: Baseline for new participants was between Day -7 and -14 (study 3080 screening visit); baseline for rollover participants was the baseline test in study 3079. During study covers both open-label titration and 52-week treatment periods
Pure tone audiometry was performed by trained personnel. During the test, the patient wore headphones and was seated in a quiet room; trained personnel manipulated the audiometry equipment to test the patient's hearing. For serial audiograms, the criteria for a clinically significant (CS) hearing change were based on the guidance from the American Speech-Language Hearing Association (ASHA) 1994 (Konrad-Martin et al 2005). These criteria included the following: greater than 20 decibels (dB) pure tone threshold shift at 1 frequency; greater than 10 dB shift at 2 consecutive test frequencies; or threshold response shifting to "no response" at 3 consecutive test frequencies.
Shifts in Electrocardiogram (ECG) Findings From Baseline to Overall Study by Participant Status
时间窗: Baseline for new participants was between Day -7 and -14 (the study 3080 screening visit); baseline for rollover participants was the last ECG in study 3079. During study ECGs were performed on weeks 24 and 52 of the open-label treatment period
A 12-lead ECG was conducted at screening, week 24, and week 52 or at the last postbaseline observation. For rollover participants, the ECG performed at the final visit of study 3079 served as the 1st ECG in study 3080. A qualified physician was responsible for interpreting the ECG. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared with baseline was considered an adverse event. For overall results, the worst postbaseline finding for the participant was summarized. Results below are formatted as Baseline ECG result - Overall ECG result.
Participants With Potentially Clinically Significant (PCS) Abnormal Laboratory Values During the Open-Label Treatment Period by Participant Status
时间窗: Day 1 - Week 52 of the open-label treatment period
Data represents participants with PCS abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * alanine aminotransferase (ALT): \>=3 times the upper limit of normal (ULN). Normal range is 6-43 U/L * aspartate aminotransferase (AST): \>=3 times ULN. Normal range is 9-36 U/L * blood urea nitrogen (BUN): \>=10.71 mmol/L * creatinine: \>=177 μmol/L * uric acid: M\>=625, F\>=506 μmol/L * white blood cell count: \<=3.0\*10\^9/L * hemoglobin: M\<=115, F\<=95 g/dL * hematocrit: M\<0.37, F\<0.32 L/L * urine blood (hemoglobin): \>=2 unit increase from baseline * urine glucose: \>=2 unit increase from baseline
Participants With Adverse Experiences
时间窗: Day 1 of open-label titration period - Week 52 of the open-label treatment period
An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Participants With Potentially Clinically Significant Abnormal Vital Signs Values by Participant Status
时间窗: Day 1 of open-label titration period - Week 52 of the open-label treatment period
Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Pulse - high: \>=120 and increase of \>= 15 beats/minute from baseline * Pulse - low: \<=50 and decrease of \>=15 beats/minute * Systolic blood pressure - high: \>=180 and increase \>=20 mmHg * Systolic blood pressure - low: \<=90 and decrease \>=20 mmHg * Diastolic blood pressure - high: \>=105 and increase of \>=15 mmHg * Diastolic blood pressure - low: \<=50 and decrease of \>=15 mmHg
次要结局
- Participant Global Assessment (PGA) of the Method of Pain Control by Participant Status(Baseline for new participants was Day 1, i.e. the first day of open-label titration. Baseline for rollover participants was the baseline in study 3079. Week 4 (end of titration, start of open-label treatment), Week 52, last visit up to Week 52)
- Current Opioid Misuse Measure (COMM) Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status(Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration Period. Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52)
- Participants by Risk Category for Aberrant Drug Misuse Based on the Total Score in the Screener and Opioid Assessment for Patients With Pain - Revised (SOAPP-R)(End of Open-label Titration Period. Weeks 4 and 24 of the Open-label Treatment Period)
- Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status(Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52)