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
Overview
- Phase
- Phase 3
- Intervention
- Plecanatide
- Conditions
- Functional Constipation
- Sponsor
- Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
- Enrollment
- 648
- Locations
- 1
- Primary Endpoint
- Number of Durable Overall CSBM Responders, Mean Replacement Approach
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Plecanatide
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.
Intervention: Plecanatide
Outcomes
Primary Outcomes
Number of Durable Overall CSBM Responders, Mean Replacement Approach
Time Frame: 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.
Secondary Outcomes
- 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)