12-Week Study of Plecanatide for CIC (The CIC3 Study)

A Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic Constipation (The CIC3 Study)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01982240

Enrollment

1394

Registered

2013-11-13

Start date

2013-11-30

Completion date

2015-06-30

Last updated

2019-12-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Idiopathic Constipation

Keywords

CIC, Constipation, Chronic Constipation, Synergy, Plecanatide

Brief summary

The purpose of this study is to confirm that the investigational medication, plecanatide, is safe and effective in treating chronic idiopathic constipation.

Detailed description

This is a randomized, 12-week, double-blind, placebo-controlled, study in approximately 1350 adult male and female patients with CIC comparing 2 doses of plecanatide to placebo. The study will be conducted at approximately 180 clinical study sites in the United States (US) and Canada. The primary objective of the study is to evaluate the efficacy and safety of 3.0 and 6.0 mg of plecanatide administered once daily (QD) for 12 weeks in a population of patients with CIC. The study population will include only patients without other causes of constipation or other chronic conditions that could interfere with study assessments. Patients may not take laxatives (with the exception of the study-provided rescue medication, bisacodyl 5mg tablets), or a number of prohibited drugs that are known to cause constipation or diarrhea, during study participation. There are 6 scheduled study visits, including the screening and follow-up visits. The planned duration of participation in this study will be 112 days and up to 155 days, with washout and all visit windows considered.

Interventions

DRUGPlecanatide

Plecanatide tablets QD for 12 weeks

DRUGPlacebo

Matching placebo tablets QD for 12 weeks

DRUGBisacodyl

Rescue medication

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Male or female aged 18-80, inclusive * Meets modified Rome III criteria for functional chronic idiopathic constipation for at least 3 months with symptom onset for at least 6 months * Completed a colonoscopy in accordance with AGA colon cancer screening guidelines (5 years), with no clinically significant findings * Willing to maintain a stable diet during the study

Exclusion criteria

* Loose stool (mushy) or watery (Bristol score 6 or 7) stool in the absence of any laxative or prohibited medicine for \> 25% of BMs during the 3 months prior to screening visit OR during the 14 day pre-treatment assessment * Active peptic ulcer disease, diabetes or hypertension not adequately treated or not stable * History of cathartic colon, laxative, enema abuse, or ischemic colitis * Fecal impaction within 3 months of screening * Patient has had /has any: diseases or conditions associated with constipation (GI or CNS), structural abnormality of the GI tract or gastric bypass surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, anal fissures or any disease or condition that can affect GI motility or defecation or can be associated with abdominal pain * Unexplained and clinically significant alarm symptoms including lower GI bleeding, iron-deficiency anemia, weight loss or systemic signs of infection or colitis * Major surgery, stroke or MI within 60 days of screening * Participated in a previous plecanatide clinical trial

Design outcomes

Primary

Measure	Time frame	Description
Number of Durable Overall CSBM Responders , Mean Replacement Approach	12-week Treatment Period	A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, included at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation.

Secondary

Measure	Time frame	Description
Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach	12-Week Treatment Period	A Complete Spontaneous Bowel Movement (CSBM) was a Bowel Movement (BM) that occurred in the absence of laxative use within 24 hours of the BM and the patient reported a feeling of complete evacuation. A weekly responder had 3 or more CSBMs and an increase of at least one CSBM from baseline in the same week.
Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach	12-Week Treatment Period	The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was assessed. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly SBM totals were derived from the daily diary entries reported during the Treatment Period in the BM and Symptom Diary.
Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach	12-Week Treatment Period	The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale \[BSFS\] from 1 to 7. 1. = separate hard lumps like nuts (difficult to pass) 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on its surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges (passed easily) 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces (entirely liquid)
Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach	12-Week Treatment Period	Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly average straining score was derived from the straining scores reported during the Treatment Period in the Daily Symptom Diary. The severity of straining during bowel movements was assessed on a 5-point Likert scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.

Countries

Canada, United States

Participant flow

Pre-assignment details

The data are correct and approved in the NDA. 1394 randomized subj.including 69 (index and non-index) duplicate subj. The index subj (21) were duplicate appeared the first time in the study and the same subject appeared in other studies or sites were non-index duplicate (48) who were excluded in the ITT population (1346).

Participants by arm

Arm	Count
Placebo Matching placebo tablets QD for 12 weeks	452
Plecanatide 3.0 mg Plecanatide tablets 3.0 mg QD for 12 weeks	453
Plecanatide 6.0 mg Plecanatide tablets 6.0 mg QD for 12 weeks	441
Total	1,346

Baseline characteristics

Characteristic	Plecanatide 6.0 mg	Placebo	Plecanatide 3.0 mg	Total
Age, Continuous	45.1 years	46.4 years	45.0 years	45.5 years
Sex: Female, Male Female	362 Participants	357 Participants	368 Participants	1087 Participants
Sex: Female, Male Male	79 Participants	95 Participants	85 Participants	259 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	8 / 458	38 / 474	37 / 457
serious Total, serious adverse events	4 / 458	6 / 474	5 / 457

Outcome results

Primary

Number of Durable Overall CSBM Responders , Mean Replacement Approach

A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, included at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation.

Time frame: 12-week Treatment Period