"Efficacy and Safety of Linaclotide in Chronic Constipation"

Complete Spontaneous Bowel Movement (CSBM) responder rate

Time frame · 8 weeks

Complete Spontaneous Bowel Movement (CSBM) responder rate is defined as the proportion of patients achieving 3 or more complete spontaneous bowel movements (CSBM) per week with an increase of 1 or more CSBM per week from baseline for at least 6 of the treatment weeks. Patient will be maintaining a daily stool diary from which data will be obtained and CSBM responder rate will be assessed.

Mean change in weekly SBM frequency

Time frame · 8 weeks

Mean change in weekly Spontaneous Bowel Movement (SBM) after 8 weeks from baseline.

Mean change in CSBM frequency

Time frame · 8 weeks

Mean change in weekly Complete Spontaneous Bowel Movement (CSBM) after 8 weeks from baseline

Changes in weekly stool consistency measured by Bristol Stool Form Scale (BSFS)

Time frame · 8 weeks

Change in weekly stool consistency from baseline using Bristol Stool Form Scale (BSFS). The scale consists of various stool forms from type 1 to type 7. (Type 1- separate hard lumps, like nuts and hard to pass, Type 2-sausage shaped but lumpy, Type 3- Like a sausage but with cracks on the surface, Type 4- Like a sausage or snake, smooth and soft, Type 5- soft blobs with clear cut edges, Type 6- fluffy pieces ragged edges, a mushy stool, Type 7- watery, no solid pieces, entirely liquid).

Change in average weekly bloating score

Time frame · 8 weeks

Change in average weekly bloating score from baseline to week-8 using a 5-point Likert scale . Bloating means subjective abdominal fullness or distension reported by the patient. Bloating score is evaluated on a 5-point Likert scale (From 1 to 5, higher score means worse outcome)

Change in weekly straining score

Time frame · 8 weeks

Change in weekly straining score from baseline to week-8 will be measured using 5-point Likert scale (from 1 to 5, higher score means worse outcome)

Change in weekly abdominal pain or discomfort score

Time frame · 8 weeks

Change in weekly abdominal pain or discomfort score from baseline to week-8 will be measured using 5-point Likert scale (from 1 to 5, higher score means worse outcome)

Change in satisfaction score related to defecation

Time frame · 8 weeks

Satisfaction score related to defecation will be measured using 5-point defecatory satisfaction score (Likert scale, from 1 to 5, lower score means worse outcome) and change will be compared between baseline value and week-8 value.

Patient reported adverse events

Time frame · Through study completion, an average of 10 weeks

Patient-reported adverse events associated with Linaclotide treatment will be documented according to common terminology criteria for adverse events (CTCAE grading).

Sustainability of treatment effects

Time frame · 2 week of drug free follow up period (from week-9 to week-10)

Sustainability of treatment effects: Sustainability will be defined as maintenance of improved symptom scores during the 2 week drug free follow up period after week-8 at levels that are not statistically significantly worse than end of treatment values and remain no worse than baseline. These symptom scores includes weekly spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) frequency, stool consistency measured by Bristol Stool Form scale (BSFS, from type 1 to 7), abdominal symptom scores including bloating score, straining score, abdominal pain or discomfort scores using 5-point Likert scale (1 to 5, higher score means worse outcome), satisfaction score related to defecation using 5-point Likert scale (1 to 5, Lower score means worse outcome) etc.

Potentially rebound of symptoms

Time frame · 2 week of drug free follow up period (from week-9 to week-10)

Rebound of symptoms: Rebound will be defined as worsening of symptom measures beyond baseline levels during the drug free follow up period. These symptom scores includes weekly spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) frequency, stool consistency measured by Bristol Stool Form scale (BSFS, from type 1 to 7), abdominal symptom scores including bloating score, straining score, abdominal pain or discomfort scores using 5-point Likert scale (1 to 5, higher score means worse outcome), satisfaction score related to defecation using 5-point Likert scale (1 to 5, Lower score means worse outcome) etc.