Assessing Tenapanor as a Treatment of CF-related Constipation.

Inclusion Criteria:

1. Having confirmed cystic fibrosis (either by sweat chloride or genetic testing)

2. Meeting criteria for CFrC Must include 2 of the following, with or without abdominal pain for at least 3months, with symptom onset at least 6-months prior:

• Straining in at least 25% of defecations

• Bristol Stool Scale 1-2 more than 25% of defecations (change in stool form)

• Sensation of incomplete evacuation more than 25% of defecations

• Sensation of anorectal obstruction/blockage more than 25% of defecations

• Manual disimpaction/manipulation of pelvic floor to facilitate more than 25% ofdefecations

• Fewer than 3 spontaneous bowel movements weekly (change in stool frequency)

• Loose stools rarely present without the use of laxatives

3. Willingness to avoid major dietary or lifestyle changes during study.

Exclusion Criteria:

1. Use of any antibiotic to treat infection within the 4-weeks prior to studyinitiation (stable azithromycin dosed 3-times weekly for lung function is to beallowed)

2. Inability to discontinue standing bowel regimen (including fiber, stool softener, aswell as either osmotic or stimulant laxative, pro-kinetic serotonergic agents, orother therapy) 2-weeks prior to study drug initiation (with ability to use osmoticlaxative therapy as rescue therapy only).

3. Severe CFrC as determined by study team

4. Prior tenapanor usage

5. Hospitalization within 4-weeks prior to study initiation.

6. DIOS within 4-weeks prior to study initiation.

7. Other known/suspected mechanical obstruction