Clinical trial NCT05895877: Evaluate the Efficacy and Safety of Goofice® (Elobixibat) in Patients With Chronic Constipation
Official title: A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Goofice® in Patients With Chronic Constipation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Constipation
Lead sponsor: Synmosa Biopharma Corp.
Sponsor class: INDUSTRY
First posted: 2023-06-09
Enrollment: 351
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of Goofice® in patients with chronic constipation.

Detailed description: In order to enroll appropriate patients with chronic constipation, a 2-week constipation-related symptom intensity screening period will be established to investigate the number of bowel movements just prior to the study drug treatment initiation. Eligible subjects who fulfill all selection criteria for enrollment will be randomly assigned to receive Goofice® or placebo drug with 2:1 allocation ratio. The study drug will be received once daily approximately 30 minutes before breakfast in the 12-week treatment period. The starting dosing of Goofice® / placebo will be 10 mg (2 tablets) in treatment period. It is allowed to adjust the dosage among 5, 10, and 15 mg after 7 days after treatment initiation, if the dose adjusting criteria are met depending on symptoms. After treatment period, subjects will be followed up for 4 weeks to observe the effect of discontinuing treatment.

Eligibility criteria: Inclusion Criteria:

- At provisional enrollment

1. Men or women ≥ 20 years of age.
2. Include 2 or more of the following during the last 3 months with symptom onset of at least 6 months:

   1. Straining during more than 25% of bowel movements (BMs);)
   2. Lumpy or hard stools in 25% of BMs;
   3. Sensation of incomplete evacuation in more than 25% of all BMs;
   4. Sensation of anorectal blockage or obstruction in more than 25% of BMs;
   5. Manual maneuvers required in more than 25% of BMs;
   6. Fewer than 3 BMs per week.

      In addition to having at least 2 of the above criteria, the following must also apply:

   a. Loose stools are rarely present without the use of laxatives; b. Insufficient criteria for irritable bowel syndrome (IBS).
3. Ability to provide written consent. - At time of enrollment
4. A total of SBM frequencies \< 6 times during the 2-week screening period.

Exclusion Criteria:

* At provisional enrollment

  1. Known or suspected allergy to components in elobixibat.
  2. Known or suspected organic constipation.
  3. Known or suspected symptomatic or drug-induced constipation.
  4. Known or suspected slow colon transit type constipation.
  5. Known or suspected excretory disorder constipation.
  6. Currently have or history of gastrointestinal obstruction.
  7. Currently have or history of abdominal hernia.
  8. History of laparotomy other than simple appendectomy.
  9. History of cholecystectomy or surgical or endoscopic intervention related to papillotomy.
  10. Subjects in whom the dosage regimens of medications, of which changing the dosage regimens is prohibited, will be changed after the day of informed consent.
  11. Cannot use the rescue medication (bisacodyl suppositories 10 mg).
  12. Pregnant, lactating or potentially pregnant women, women who wish to become pregnant from the time of the informed consent to the last observation/test point, or women who do not agree to use appropriate birth control methods. The acceptable effective contraception methods include: a. Male or female sterilization, implant, or intrauterine device; b. Injectable, pill, patch, ring plus one barrier method\*; c. Two combined barrier methods\*.

      * Effective barrier methods are diaphragm, male or female condoms, sponge, or spermicides (creams or gels that contain a chemical to kill sperm).
  13. Anemia, defined as hemoglobin ≤ 10 g/dL.
  14. Concurrent serious renal disease (creatinine ≥ 2.00 mg/dL) or liver disease (total bilirubin ≥ 3.0 mg/dL, or aspartate aminotransferase(AST) or alanine transaminase(ALT) ≥ 100 U/L).
  15. Concurrent clinical significant heart disease, including uncontrolled hypertension, arrhythmia, or heart failure.
  16. History of serious drug-induced allergy needs emergent medical intervention, such as anaphylaxis, angioedema, generalized urticaria or bronchospasm.
  17. Subjects have a history of cancer (other than basal cell or squamous cell carcinoma of the skin) unless the malignancy has been in a complete remission without maintenance chemotherapy for ≥ 5 years prior to the Screening visit.
  18. Subjects who are taking part in another clinical study, or subjects who take part in another clinical study within 12 weeks prior to the day of informed consent.
  19. Loss of weight greater than 5 kg one month before screening visit.
  20. Determined by the investigator to be not suitable for the conduct of the study for any other reasons.
  21. Subjects have a barium enema within 7 days of the Screening Visit.
* At time of enrollment

  22. Subjects have a clinically significant finding on colonoscopy performed as required in accordance with the American Gastroenterological Association (AGA) guidelines (within AGA time frames). If polyps are found and biopsied, pathology must be reviewed and must be negative for cancer before the subject may be enrolled in the study. 23. Used the rescue medication (bisacodyl suppositories 10 mg) at least 6 times during the 2-week screening period or subjects who used the rescue medication at least 3 times in Week -1 of the screening period. 24. Used the rescue medication for less than 72 hours after bowel movement during the 2-week screening period. 25. Mushy stool or watery stool (Bristol Stool Form Scale type 6 or 7) in SBM during the 2-week screening period. 26. Used prohibited medications/therapies during the 2-week screening period

Primary outcomes:
measure: Overall Complete spontaneous bowel movement(CSBM) responder rate during 12 weeks treatment
timeFrame: 12 weeks
Secondary outcomes:
measure: Efficacy endpoint - Complete spontaneous bowel movement (CSBM) responder rate at Week 12
timeFrame: 12 weeks
measure: Efficacy endpoint - Spontaneous bowel movement (SBM) responder rate at Week 12
timeFrame: 12 weeks
measure: Efficacy endpoint - SBM and CSBM responder rate
timeFrame: 4 weeks
measure: Efficacy endpoint - SBM frequency
timeFrame: 12 weeks
measure: Efficacy endpoint - CSBM frequency
timeFrame: 12 weeks
measure: Efficacy endpoint - Mean stool consistency by Bristol Stool Form Scale
timeFrame: 12 weeks
measure: Exploratory endpoint - Patient Assessment of Constipation Quality of Life (PAC-QoL)
timeFrame: 12 weeks
measure: Exploratory endpoint - Patient Assessment of Constipation Symptoms (PAC-SYM) scores
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital Clinical Trial Center
Study officials:
affiliation: National Taiwan University Hospital
name: Ming-Shiang Wu
role: PRINCIPAL_INVESTIGATOR
References: