A Study to Evaluate the Effectiveness and Safety of Vibegron Administered Orally for 12 Weeks to Women with Irritable Bowel Syndrome

Overview

About this study

The purpose of this study is to evaluate the effectiveness and safety of vibegron, a beta-3 adrenergic receptor (β3-AR) agonist, in the treatment of pain associated with irritable bowel syndrome (IBS) due to IBS with predominant diarrhea (IBS-D) or mixed episodes of diarrhea and constipation (IBS-M).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria: 

Subjects are eligible to be included in the study only if all of the following criteria apply at Visit 1 (Screening), unless otherwise noted:

  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form, including agreeing to patient registry verification.
  • Female, 18 to 70 years of age, inclusive.
  • Body weight ≥ 50 kg; body mass index < 45
  • Diagnosis of IBS-D or IBS-M according to the Rome IV criteria:
    • Recurrent abdominal pain, on average at least 1 day per week in the last 3 months, associated with 2 or more of the following criteria:
      • Related to defecation;
      • Associated with a change in frequency of stool;
      • Associated with a change in form (appearance) of stool.
  • Diagnostic criteria must be fulfilled for the last 3 months, with symptom onset at least 6 months before diagnosis.
  • Subtyping performed by the predominant stool pattern present in a subject:
    • IBS-D: loose, mushy, or watery stools (Bristol Type 6 or 7) for > 25% of bowel movements and hard or lumpy stools (Bristol Type 1 or 2) for < 25% of bowel movements;
    • IBS-M: hard or lumpy stools (Bristol Type 1 or 2) for > 25% of bowel movements and loose, mushy, or watery stools (Bristol Type 6 or 7) for > 25% of bowel movements.
  • Has completed a colonoscopy according to the American Gastroenterological Association criteria (if necessary), with no clinically significant findings in the last 5 years.
  • Willing and able, as assessed by the Investigator, to follow study instructions, including completing the subject diaries and quality of life questionnaires and attending all study visits.
  • Willing and able to maintain regular diet for the duration of the study.
  • Has no clinically significant findings on a physical examination or clinical laboratory tests that could interfere with study participation or confound study assessments, in the opinion of the Investigator. Serum tissue transglutaminase antibody (IgA) must be negative. Fecal calprotectin testing is optional and should only be considered if there is a strong suspicion that the subject has IBD (e.g., family history in a 1st degree relative, other genetic factors, etc.) or other organic disease, according to the clinical judgement of the investigator.
  • Women of childbearing potential must agree to use one of the contraception methods.
  • Agrees not to participate in another clinical trial while participating in this study.
  • At Baseline (Visit 3):
    • Must continue to meet all inclusion criteria.
    • During any 5 days in the 7 days immediately prior to Baseline (Visit 3), as reported in the subject’s daily pain diary:
      • Subject must have a weekly average of “worst abdominal pain in the past 24 hours” score of ≥ 3.0 on a 0- to 10-point NRS.

Exclusion Criteria:

  • Diagnosis of IBS-C or IBS-U per Rome IV criteria.
  • History of chronic idiopathic constipation or functional constipation.
  • Current or history (in the past year) of substance or alcohol abuse, alcoholism, alcohol addiction, or drinks > 3 alcoholic beverages per day (one drink defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of distilled spirits).
  • History of clinically relevant liver disease or severe hepatic impairment (Child-Pugh Class C).
  • Pre-existing condition that has altered normal gastrointestinal anatomy (e.g., prior bariatric surgery or gastric banding, solitary rectal ulcer syndrome).
  • History of or suspected mechanical gastrointestinal obstruction or current symptoms suggestive of gastrointestinal obstruction or infection.
  • Diverticulitis within prior 3 months.
  • Structural abnormality of the gastrointestinal tract or a disease or condition that can affect gastrointestinal motility.
  • History of a gastrointestinal motility disorder other than IBS (e.g., gastroparesis, intestinal pseudo-obstruction, achalasia, Parkinson’s disease, multiple sclerosis, spinal cord injury).
  • Severe constipation or sequelae from constipation.
  • Active duodenal or gastric ulcer.
  • History of solitary rectal ulcer syndrome.
  • Prior history of a gastrointestinal malignancy, inflammatory bowel disease, celiac disease.
  • History of colitis (ischemic, lymphocytic, collagenous or radiation-induced) or hepatic and/or renal function that could interfere with the absorption, metabolism and/or excretion of the study drug (eg, carcinoid syndrome, amyloidosis).
  • Uncomplicated appendectomy within the past 3 months; subjects who had an appendectomy that was associated with any related complications or sequelae are eligible if the procedure was performed at least 6 months prior and all complications/sequelae have resolved.
  • Planned gastrointestinal or abdominal surgery within the next 6 months.
  • Co-existing gastroesophageal reflux disease or functional dyspepsia with symptoms predominant to IBS symptoms.
  • Symptoms or diagnosis of a medical condition other than IBS that may contribute to abdominal pain (e.g., interstitial cystitis; fibromyalgia currently being treated with pregabalin or gabapentin; and endometriosis with uncontrolled abdominal pain).
  • History of pancreatitis, structural diseases of the pancreas (including known or suspected pancreatic duct obstruction), known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction; acute, symptomatic cholecystitis or symptomatic cholelithiasis within the last 6 months is also exclusionary.
  • Lactose intolerance not controlled by lactose-free diet.
  • History or evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery, percutaneous transluminal coronary angioplasty, cerebrovascular accident, transient ischemic attack, or any clinically significant cardiac disease.
  • Clinically significant electrocardiogram (ECG) abnormality that, in the opinion of the Investigator, exposes the subject to risk by participating in the study.
  • Uncontrolled hypertension (sitting systolic blood pressure ≥ 180 mmHg and/or sitting diastolic blood pressure ≥ 100 mmHg) or resting heart rate (by pulse) > 100 beats per minute.
  • Systolic blood pressure ≥ 160 mmHg but < 180 mmHg is excluded unless deemed by the Investigator as safe to proceed in this study and agreed to by the Sponsor’s designated Medical Monitor; must be on stable hypertension medication for at least 3 months prior to entering Run-in (Visit 2).
  • Concurrent malignancy or history of any malignancy (within the last 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
  • Uncontrolled diabetes mellitus defined by a hemoglobin A1C level > 8%.
  • Significant psychiatric or psychologic disorder that would preclude meaningful participation in the study (e.g., bipolar disorders or schizophrenia; however, treated depression on a stable regimen [e.g., SNRI, SSRI] is allowed) in the opinion of the Investigator .
  • Presence of any unexplained alarm symptoms (e.g., anemia, gastrointestinal bleeding, unintentional weight loss, suspected malignancy).
  • Use of any prohibited medications, such as eluxadoline, for which a subject cannot complete the appropriate washout period.  Positive urine drug screen at Visit 1 is exclusionary except for the following situations:
    • Subjects who hadve a positive urine drug screen at Visit 1 due to a prohibited concomitant medication that can be washed out, the urine drug screen must be repeated at Visit 2 to determine if sufficient washout of the prohibited concomitant medication has occurred and to confirm eligibility.
    • If the initial positive result at Visit 1 was due to a permitted concomitant medication, based on the clinical judgment of the investigator, a subject is still eligible and the urine drug screen doeswould not need to be retested at Visit 2
  • Dose change for any medications requiring a stable dose prior to the Screening Visit or plans to initiate or change the dosing of any of these medications during the study.
  • Currently participating in or has participated in a study with an investigational compound or device or procedure within 28 days prior to screening.
  • Currently participating in or has participated in a study with vibegron.
  • ALT or AST > 2.0 times upper limit of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).
  • Lipase > 2 x ULN.
  • Estimated glomerular filtration rate < 30 mL/min/1.73 m^2.
  • Women who are pregnant, nursing, or planning a pregnancy during the study.
  • History of sensitivity to any of the study drugs, or components thereof, or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates study participation.
  • At Baseline (Visit 3):
    • Noncompliant with dosing during the 2-week Run-in Period (taking < 80% or > 120% of study medication).
    • Clinically significant medical or surgical history or any condition that could interfere with study participation or confound the assessments in the opinion of the study Investigator.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Jacksonville, Fla.

Mayo Clinic principal investigator

Brian Lacy, M.D., Ph.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20461646

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