A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Plecanatide in the Treatment of Functional Constipation in Chinese Patients for up to 12 Weeks
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 648
- 试验地点
- 1
- 主要终点
- Number of Durable Overall CSBM Responders, Mean Replacement Approach
研究概览
简要总结
This is a multi-center, randomized, double-blind, Placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Plecanatide in the treatment of Functional Constipation in Chinese patients for up to 12 weeks.
Patients will enter a Screening period which must undergo a 2-week Pre-Treatment assessment, they will complete daily assessments of electronic dairy to demonstrate the eligibility.
Eligible subjects will be randomized into Plecanatide 3 mg group or Placebo group at Visit 1 at the ratio of 1:1 and take an oral dose of study treatment continuously for 12 weeks. For 2 weeks after complete dosing patients will continue to complete daily electronic dairy. Patients will then return to the clinical site for efficacy and safety assessment as part of an End of Study visit. The planned duration of participation in this study will be 154 days and up to 164 days with all windows considered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is willing and able to participate in the study for the required duration, can understand and is willing to sign the （Inform Consent Form)ICF and agrees to undergo all protocol-related tests and procedures.
- •Males or females over 18 years of age (inclusive) when signed the （Inform Consent Form)ICF.
- •Patient agrees to use adequate medical contraception from signing of informed consent through 28 days after the first dose of study drug
- •Colonoscopy with normal or mildly abnormal results.
- •Patient meets the Rome Ⅳ functional constipation criteria as modified for this study for at least 3 months prior to the Screening visit with symptom onset for at least 6 months prior to the diagnosis. The Rome Ⅳ criteria as modified for this study require the following:
- •Patients who meet the modified Rome Ⅳ criteria based on history must also demonstrate the following during the two-week Pre-Treatment Electronic hand-held device(EHD) assessment period.
- •Patient must complete at least 6 of the 7 daily (Electronic Diary) eDiary entries during each week of the 2-week pre-treatment assessment period.
- •Patient is able to communicate with Investigator and understand and comply with scheduled visits, study treatment, laboratory tests, and other study-related procedures and requirements during the study.
排除标准
- •Previous use of Plecanatide.
- •Previous anaphylactic reaction to any medication.
- •Females are excluded if lactating.
- •Patient has unexplained and clinically significant "alarm symptoms" including nonhemorrhoidal lower Gastrointestinal (GI) bleeding, iron-deficiency anemia, weight loss.
- •Patient with known constipation due to secondary causes.
- •Patient had a known structural abnormality of the gastrointestinal tract or a condition that may affect gastrointestinal motility or defecation
- •Patient had a history of chronic disease with abdominal pain or discomfort that would interfere with the evaluation of this study
- •Patient has active peptic ulcer.
- •Patient has had or is scheduled to have abdominal surgery during the study.
- •Patient has fecal impaction requiring hospitalization or emergency room treatment.
- •Patient has traveled to a region considered as high risk for developing traveler's diarrhea while participating in the study.
- •Patient has a history of cancer (other than basal cell or squamous cell carcinoma of the skin) unless the malignancy has been in a complete remission without maintenance chemotherapy for at least 5 years prior to the Screening visit.
- •Known or suspected alcoholism or drug addiction or significant drug abuse within 1 year of the Screening visit.
- •Patient has a history of diabetic neuropathy.
- •Patient has hypothyroidism.
- •Patient has active HBV、HCV or HIV antibody positive.
- •Patient with severe cardiopulmonary or other organ dysfunction.
- •Patient with significant abnormalities in physical examination, ECG, or laboratory tests that, in the judgment of the investigator, would make the patient inappropriate for this study.
- •Evaluation of BSFS not met before administration。
- •Patient uses Dulcolax® within 72 hours before the first dose of study drug.
- •Patient reports the use of rescue medication (Dulcolax®). for ≥3 days in either of the two weeks in the Pre-Treatment Assessment period.
- •Use of concomitant medications not allowed by the protocol prior to randomization。
- •Hospitalization for psychiatric disorder or suicide attempt within 2 years before the screening visit。
- •Patient reports participation in a clinical study within 30 days of the Screening visit or Five half-lives prior to visit
- •Other circumstances in which the investigator considers the subject inappropriate for study participation.
研究组 & 干预措施
Plecanatide group(n=320)
The investigational products are administrated orally, each patient will take one table (Plecanatide 3.0mg) Once daily(QD) in the day before 18:00 with approximately of water. If the investigational product is not taken in the day before 18:00 then skip the dose on that day and take the next dose on the next regular time. The duration of treatment is 12 weeks.
干预措施: Plecanatide (Drug)
Placebo group (n=320)
The investigational products are administrated orally, each patient will take one table (Placebo 3mg) QD in the day before 18:00 with approximately of water. If the investigational product is not taken in the day before 18:00 then skip the dose on that day and take the next dose on the next regular time. The duration of treatment is 12 weeks.
干预措施: Plecanatide (Drug)
结局指标
主要结局
Number of Durable Overall CSBM Responders, Mean Replacement Approach
时间窗: 12-Week Treatment Period
The primary efficacy endpoint will be the proportion of patients who are overall Complete spontaneous bowel movement (CSBM) responders during the 12-week Treatment Period. A CSBM weekly responder is defined as a patient who has ≥ 3 CSBMs per week and an increase from baseline of ≥ 1 CSBM for that week. An overall CSBM responder is a patient who is a weekly CSBM responder for at least 9 of the 12 treatment weeks, including at least 3 of the last 4 weeks.
次要结局
- Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach(Baseline and 12 weeks)
- Change From Baseline in SBMs (SBMs/Week) Over the 12-week Treatment Period, Mean Replacement Approach(Baseline and 12 weeks)
- Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach(Baseline and 12 weeks)
- Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach(Baseline and 12 weeks)
- Percent of Patients with an SBM within 24 Hours of the First Dose(Baseline and 12 weeks)
- Percent of Patients with a CSBM within 24 Hours of the First Dose(Baseline and 12 weeks)
- Patient Reported Symptoms Associated With Constipation(Baseline and 12 weeks)
- Use of Rescue Medication(Baseline and 12 weeks)
- Patient Assessment of Constipation - Symptoms - (PAC-SYM©)(Baseline and 12 weeks)
- Treatment Satisfaction(Baseline and 12 weeks)
- Time to First CSBMs and SBMs, Mean Replacement Approach(Baseline and 12 weeks)
- Patient Global Assessments(Baseline and 12 weeks)
- Patient Assessment of Constipation- Quality of Life- (PAC-QOL©)(Baseline and 12 weeks)