Clinical trial NCT05151328: Efficacy and Safety of Plecanatide Comparing With Placebo in the Treatment of Functional Constipation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Functional Constipation
Lead sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-12-09
Enrollment: 648
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Males or females over 18 years of age (inclusive) when signed the （Inform Consent Form)ICF.
3. Patient agrees to use adequate medical contraception from signing of informed consent through 28 days after the first dose of study drug
4. Colonoscopy with normal or mildly abnormal results.
5. 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:
6. 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.
7. 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.
8. 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:

1. Previous use of Plecanatide.
2. Previous anaphylactic reaction to any medication.
3. Females are excluded if lactating.
4. Patient has unexplained and clinically significant "alarm symptoms" including nonhemorrhoidal lower Gastrointestinal (GI) bleeding, iron-deficiency anemia, weight loss.
5. Patient with known constipation due to secondary causes.
6. Patient had a known structural abnormality of the gastrointestinal tract or a condition that may affect gastrointestinal motility or defecation
7. Patient had a history of chronic disease with abdominal pain or discomfort that would interfere with the evaluation of this study
8. Patient has active peptic ulcer.
9. Patient has had or is scheduled to have abdominal surgery during the study.
10. Patient has fecal impaction requiring hospitalization or emergency room treatment.
11. Patient has traveled to a region considered as high risk for developing traveler's diarrhea while participating in the study.
12. 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.
13. Known or suspected alcoholism or drug addiction or significant drug abuse within 1 year of the Screening visit.
14. Patient has a history of diabetic neuropathy.
15. Patient has hypothyroidism.
16. Patient has active HBV、HCV or HIV antibody positive.
17. Patient with severe cardiopulmonary or other organ dysfunction.
18. 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.
19. Evaluation of BSFS not met before administration。
20. Patient uses Dulcolax® within 72 hours before the first dose of study drug.
21. Patient reports the use of rescue medication (Dulcolax®). for ≥3 days in either of the two weeks in the Pre-Treatment Assessment period.
22. Use of concomitant medications not allowed by the protocol prior to randomization。
23. Hospitalization for psychiatric disorder or suicide attempt within 2 years before the screening visit。
24. Patient reports participation in a clinical study within 30 days of the Screening visit or Five half-lives prior to visit 1.
25. Other circumstances in which the investigator considers the subject inappropriate for study participation.

Primary outcomes:
measure: Number of Durable Overall CSBM Responders, Mean Replacement Approach
timeFrame: 12-Week Treatment Period
Secondary outcomes:
measure: Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in SBMs (SBMs/Week) Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Treatment Satisfaction
timeFrame: Baseline and 12 weeks
measure: Time to First CSBMs and SBMs, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Percent of Patients with an SBM within 24 Hours of the First Dose
timeFrame: Baseline and 12 weeks
measure: Percent of Patients with a CSBM within 24 Hours of the First Dose
timeFrame: Baseline and 12 weeks
measure: Patient Reported Symptoms Associated With Constipation
timeFrame: Baseline and 12 weeks
measure: Use of Rescue Medication
timeFrame: Baseline and 12 weeks
measure: Patient Global Assessments
timeFrame: Baseline and 12 weeks
measure: Patient Assessment of Constipation- Quality of Life- (PAC-QOL©)
timeFrame: Baseline and 12 weeks
measure: Patient Assessment of Constipation - Symptoms - (PAC-SYM©)
timeFrame: Baseline and 12 weeks
Other outcomes:
measure: Safety Endpoints
timeFrame: Baseline and 12 weeks
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
References: