A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of Olorinab in Subjects With Irritable Bowel Syndrome Experiencing Abdominal Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 273
- 试验地点
- 69
- 主要终点
- Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12
研究概览
简要总结
The purpose of this study is to determine whether olorinab is a safe and effective treatment for abdominal pain in participants with irritable bowel syndrome (IBS).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of irritable bowel syndrome (IBS) with predominant constipation (IBS-C) or predominant diarrhea (IBS-D) according to Rome IV criteria at Visit 1 (Screening)
- •Per the Rome IV diagnostic algorithm for IBS, participants 50 years of age and over are to have had one of the following with a result that rules out causes of abdominal pain other than IBS:
- •Colonoscopy (within 10 years of Visit 1 [Screening])
- •Flexible sigmoidoscopy and double contrast barium enema (within 5 years of Visit 1 [Screening])
- •Computed tomography colonography (within 5 years of Visit 1 [Screening])
排除标准
- •Diagnosis of IBS with mixed bowel habits (IBS-M) or unsubtyped IBS (IBS-U)
- •Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 (Screening) that may confound efficacy assessments in the clinical judgment of the Investigator (or designee)
- •Any colonic or major abdominal surgery (eg, bariatric surgery [including gastric banding], stomach surgery, small/large bowel surgery, or abdominal large vessel surgery). History of cholecystectomy is exclusionary for participants with IBS-D. For participants with IBS-C, a history of cholecystectomy more than 6 months prior to Visit 1 (Screening) is allowed. Procedures such as appendectomy, hysterectomy, caesarean section, or polypectomy are allowed as long as they have occurred at least 3 months prior to Visit 1 (Screening).
- •Long-Term Extension Inclusion Criteria:
- •All participants must have completed the Main Study (including both Visit 8 [Week 12] and Visit 9 [Week 14])
- •Long-Term Extension Exclusion Criteria:
- •Participant meets any exclusion criteria from the Main Study at the time of assessing eligibility for the LTE, unless approved by the Sponsor in advance.
- •Participant had less than 75% overall compliance with eDiary entries during the Main Study.
- •Participant deviated from the prescribed dosage regimen during the Main Study (ie, overall study treatment compliance less than 85% or more than 115%), unless approved by the Sponsor in advance.
研究组 & 干预措施
Placebo (Main Study)
干预措施: Placebo (Drug)
Olorinab low dose (Main Study)
干预措施: Olorinab (Drug)
Olorinab medium dose (Main Study)
干预措施: Olorinab (Drug)
Olorinab high dose (Main Study)
干预措施: Olorinab (Drug)
Olorinab (Long-Term Extension)
Participants will receive olorinab based on their treatment assignment in the Main Study.
干预措施: Olorinab (Drug)
结局指标
主要结局
Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12
时间窗: Baseline and Week 12
The APS is a single question, 11-point numeric rating scale in which 0 represents no abdominal pain and 10 represents the worst possible abdominal pain. The change in AAPS from Baseline at Week 12 was analyzed using a mixed-effects model repeated measures (MMRM) analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. An unstructured variance-covariance matrix was used for the MMRM analysis.
Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to 14 Weeks
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
LTE Period: Number of Participants With TEAEs and SAEs
时间窗: Up to 54 Weeks
An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
时间窗: Baseline to Week 14
Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters
时间窗: Baseline to Week 54 (of LTE)
Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs
时间窗: Baseline to Week 14
Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), heart rate (HR), body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.
LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs
时间窗: Baseline to Week 54 (of LTE)
Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), HR, body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.
次要结局
- Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12(Baseline and Week 12)
- Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks(Baseline and Week 12)
- Main Study: Percent Change From Baseline in AAPS at Week 12(Baseline and Week 12)
- Main Study: Change From Baseline in Number of Pain-Free Days at Week 12(Baseline and Week 12)
- Main Study: Maximum Concentration (Cmax) of Olorinab(On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose)
- Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab(On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose)
- Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab(Pre dose on Day 1, Day 2 and Weeks 2, 4, 8, 10 and 12)