Phase 3 Study to Evaluate the Long-Term Safety and Tolerability of CB-5945 for the Treatment of Opioid-Induced Constipation in Adults Taking Opioid Therapy for Chronic Non-Cancer Pain
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1,407
- 主要终点
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the long-term safety and tolerability of CB-5945 for the treatment of opioid-induced constipation (OIC) in adults taking opioid therapy for chronic non-cancer pain.
详细描述
This is a multicenter, double-blind, placebo-controlled, parallel-group study in participants with OIC taking opioid therapy for chronic non-cancer pain. Approximately 1,400 participants (approximately 700 participants per treatment group) with OIC will be randomized at approximately 225 study centers to receive either 0.25 milligrams (mg) CB-5945 twice daily (BID) or a matching placebo BID for the 52-week double-blind treatment period, followed by a 4-week follow-up period. All randomized participants will be evaluated for safety, tolerability, and quality of life from the first dose of study drug through Week 56.
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
- •Is taking a stable daily dose of opioids of ≥30-mg morphine-equivalent total daily dose (METDD) for chronic non-cancer pain
- •Has constipation that is caused by the chronic use of opioids
- •Is willing to use only the study-provided laxative(s) and to discontinue use of all other laxatives, enemas, stool softeners, and other medications to treat constipation (for example, lubiprostone) during the study period (from Screening until the last study assessment).
- •Is able and willing to refrain from facilitating defecation via manual maneuvers (for example, digital evacuation or support of the pelvic floor) during the study period (from Screening to the last study assessment)
排除标准
- •Has gastrointestinal (GI) or pelvic disorders known to affect bowel transit (for example, obstruction) or contribute to bowel dysfunction
- •Has evidence of intestinal obstruction
- •Has a history of rectal bleeding not due to hemorrhoids or fissures
- •Has an active malignancy of any type (participants with a history of successfully treated malignancy >5 years before the scheduled administration of study medication and participants with treated basal or squamous cell cancer may be enrolled)
- •Is taking antispasmodics (for example, dicyclomine), antidiarrheals (for example, loperamide), prokinetics (for example, metoclopramide), or locally acting chloride channel activators (for example, lubiprostone)
- •Is taking non-opioid medications known to cause constipation (for example, iron sulfate therapy or tricyclic antidepressants)
研究组 & 干预措施
CB-5945
0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks
干预措施: CB-5945 (Drug)
Placebo
Placebo, administered orally, BID for 52 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline through Week 56
A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included "possibly related" or "related" as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
次要结局
- Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52(Baseline, Weeks 49-52)
- Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52(Baseline, Week 52)
- Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52(Baseline, Week 52)
- Plasma Trough Concentrations of CB-5945(Weeks 4, 12, 24, 36, and 52)