| Eligibility |
Inclusion Criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female patients aged 18 to 70 years of age, inclusive.
3. Patients with FC as defined by the ROME IV diagnostic criteria for FC.
Diagnostic criteria for FC*:
- Must include 2 or more of the following:
1. Straining during more than one-fourth (25%) of defecations
2. Lumpy or hard stools (Bristol Stool Form Scale 1 or 2) more than one-fourth
(25%) of defecations
3. Sensation of incomplete evacuation more than one-fourth (25%) of defecations
4. Sensation of anorectal obstruction/blockage more than one-fourth (25%) of
defecations
5. Manual maneuvers to facilitate more than one-fourth (25%) of defecations
(such as digital evacuation, or support of the pelvic floor)
6. Fewer than 3 SBMs per week
- Loose stools are rarely present without the use of laxatives
- Insufficient criteria for irritable bowel syndrome (IBS). *Criteria fulfilled for
the last 3 months with symptom onset at least 6 months prior to diagnosis.
4. Patient has less than 3 SBMs/week within 2 weeks prior to the Screening Visit.
5. Patient has completed a colonoscopy with no clinically significant findings which meet
other exclusion criteria within 12 months prior to Screening or at the Screening
Visit.
6. Patient must agree that after the Visit 2 (Run-in Visit) they will discontinue any
prohibited medications, laxatives (prescription and over-the-counter), supplemental
fibers, or traditional medicine taken for abdominal symptoms or constipation as
defined per protocol except the rescue medication, provided by the study site and
following the Investigator's instructions for its use. Patient should not take rescue
medication (bisacodyl) on the calendar day before and the calendar day of the start of
the Treatment Period (Visit 3). If the wash-out criteria are not achieved on Visit 3,
the Visit could be postponed once.
7. Patient must agree to use and comply with the diet guidance provided in applicable
Chronic Constipation Treatment Guideline starting after the Screening Visit and during
the study until End of Study.
8. Ability of patient to swallow tablets.
9. A co-operative attitude and ability to perform all study related procedures and to
correctly use the diary.
Exclusion Criteria:
1. Patient with history of surgical resection of stomach, gallbladder, small intestine,
large intestine, and bariatric surgery (excluding resection of appendicitis and benign
polyp).
2. Patient with history or current affection of inflammatory bowel disease (Crohn's
disease or ulcerative colitis) and celiac disease.
3. Patient with diagnosis of IBS (constipation, diarrhea, or mixed).
4. Patient with history or current ischemic colitis.
5. Patient currently with infectious enteritis or enterocolitis. Patients with
asymptomatic diverticulosis, diagnosed during the colonoscopy can be enrolled, unless
previous history of diverticulitis.
6. Patient currently with hyperthyroidism or hypothyroidism (unless adequately treated),
or patients who have a thyroid-stimulating hormone outside of the laboratory reference
range at Visit1.
7. Patient with apparent mechanical obstruction (ie, patient with ileus caused by
hernia).
8. Patient has a structural abnormality of the GI tract or a disease or history of a
condition that can affect GI motility.
9. Patient has ever had any of the following diseases or conditions that can be
associated with constipation: pseudo-obstruction, colonic inertia, megacolon,
megarectum, bowel obstruction, descending perineum syndrome, solitary rectal ulcer
syndrome, and systemic sclerosis.
10. Patient currently affected by constipation due to anorectal disease, affecting the
anorectal area such as anal fissure, anorectal fistulas, hemorrhoidal disease Grade
III and IV, and bleeding hemorrhoids.
11. Patient currently has both unexplained and clinically significant alarm symptoms
(lower GI bleeding, rectal bleeding or heme-positive stool, iron-deficiency anemia or
any unexplained anemia, or weight loss) or systemic signs of infection or colitis.
12. Patient currently affected by drug-induced constipation.
13. Patient with constipation due to other organic disease.
14. Patient currently affected by active peptic ulcer (ie, disease that is not adequately
treated or stable with therapy).
15. In the case of a female, the one currently affected by endometriosis or uterine
adenomyosis.
16. Patient with uncontrolled severe depression, anxiety, or any eating disorder
considered by the Investigator to influence drug evaluation.
17. Patient has a potential central nervous system cause of constipation (eg, Parkinson's
disease, spinal cord injury, and multiple sclerosis.).
18. Patients with uncontrolled and unstable diabetes mellitus with reported episodes of
hypoglycemia within 1 year prior to Screening or history of diabetic neuropathy.
19. Patient with history of abuse of drug or alcohol within 1 year before consent
acquisition, or with current abuse.
20. Patient with history of or current diagnosis of any cancer (except for nonmelanoma
skin cancer which has been removed) diagnosed less than 5 years prior to Screening.
Patients with cancer in full remission more than 5 years after diagnosis are
acceptable.
21. Patient with major surgery or any other condition that may require use of narcotic
drugs or general anesthesia within 60 days of Screening and during the study.
22. Any clinically significant abnormality identified by physical examination,
electrocardiogram (ECG) or laboratory tests, which in the judgment of the Investigator
would compromise the patient's safety or successful participation in the clinical
study, or any of the following laboratory findings:
1. Male hemoglobin < 12 g/dL (< 120 g/L) and female hemoglobin < 10 g/dL (< 100 g/L)
at Screening.
2. Male serum creatinine = 1.5 mg/dL and female serum creatinine = 1.4 mg/dL, or
creatinine clearance = 60 mL/min based on calculation using the Cockcroft-Gault
formula: ([140-age in years] × weight in kg)/(72 × [creatinine in mg/dL]). For
women, multiply result by 0.85.
3. Active liver disease and/or significant abnormal liver function defined as
aspartate aminotransferase > 2 × upper limit of the normal (ULN) and/or alanine
aminotransferase > 2 × ULN and/or total bilirubin > 1.5 × ULN.
4. Patient with stool blood positive at Screening.
23. Patient currently affected by clinically significant cardiovascular disease,
respiratory disease, kidney disease, hepatic disease, GI disease (excluding FC),
hematology disease, endocrine disease, hemorrhagic disease, or neural/mental disease
or other disease or condition that might, in the judgment of the Investigator, place
the patients at undue risk or potentially compromise the results of interpretation of
the study results.
24. Patient with history of drug allergy to any active or inactive ingredient of
pradigastat.
25. Patients who are vegetarian or vegan.
26. Pregnant or nursing (lactating) women.
27. Women of childbearing potential, unless they are using effective methods of
contraception during study.
28. Male, who are attempting to naturally father a child or donate sperm.
29. Patients who have received an investigational drug within 30 days or 5 half-lives
(whichever is greater) prior to the Screening Visit.
30. Patients participating to another clinical study at any time during this study.
Studies that require consent only to store data and that do not require Follow-up are
not considered to be observational or interventional and are exempted from this
exclusion.
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