An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation

The purpose of the study is to evaluate efficacy, safety, and pharmacokinetics (PK) of oral
Plecanatide 0.5, 1.0 and 1.5 mg tablets dosed once a day as compared to matching placebo,
when administered for 8 weeks in adolescents with chronic idiopathic constipation.

This study will consist of a 4-week screening period, 8 weeks of treatment, and a 2-week
follow-up. The study will assess the effects of Plecanatide on bowel movement frequency and
other clinical features of CIC.

Key Inclusion Criteria:

1. Male or female adolescents 12 to less than 18 years of age.

2. Diagnosed with CIC based on the Rome III criteria for child/adolescent functional
constipation (Appendix A).

3. Patient is able to voluntarily provide written, signed, and dated (personally and via
a legally authorized representative [LAR]) assent/informed consent as applicable to
participate in the study.

4. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully
comply with study procedures (e.g., accept venipuncture, willing and able to swallow
tablets, accept urine drug screen for opiates) and restrictions.

Key Exclusion Criteria:

1. The patient has a mental age <4 years in the investigator's opinion.

2. The patient has previously been diagnosed with anorectal malformations, neurological
deficits, or anatomical anomalies that would constitute a predisposition to
constipation.

3. The patient currently requires iron supplements, amitriptyline, or other tricyclic
antidepressants for depression, opioid-containing medications or compounds for pain,
or has other conditions that require medications known to cause constipation. A
patient with an onset of constipation prior to the use of these medications and who
has been on a stable dose for at least 8 weeks prior to Screening might be considered
eligible for this study if the investigator deems these medications do not
significantly contribute to the patient's constipation. Screening of these patients
needs to be approved by the medical monitor and the sponsor.

4. The patient, if female of childbearing potential (defined as postmenarche), does not
agree to practice 1 of the following medically acceptable methods of birth control
throughout the study:

- Hormonal methods such as oral, implantable, injectable, vaginal ring, or
transdermal contraceptives for a minimum of 1 full cycle (based on the patient's
usual menstrual cycle period) before study drug administration.

- Total abstinence from sexual intercourse since the last menses before study drug
administration.

- Intrauterine device.

- Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or
cream.

5. The patient follows a diet not considered normal by the investigator for the patient's
age, relative to variety of food, caloric content, and quantity. The patient must have
been on a stable diet for at least 30 days weeks prior to Screening.

6. The patient's mobility or normal exercise tolerance is compromised in the
investigator's opinion.

7. The patient has a history of an eating disorder.