Efficacy, Safety and Tolerability of Enteric-Coated Cholestyramine Capsules for Adult Short Bowel Syndrome

NCT04046328 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: PMS-2018-0022018-004419-32
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

A new Enteric-Coated Cholestyramine (ECC) capsule has been developed to manage diarrhea associated with Short Bowel Syndrome (SBS) in adults. The formulation is expected to release cholestyramine in the remaining segment of the small intestine in SBS patients, thus binding bile acids after fat digestion, but before induction of diarrhea in the colon. The delayed-release profile is also expected to help reduce the potential for drug-drug interactions occurring in the proximal small intestine. Two doses of ECC will be studied for efficacy, safety and tolerability in this Phase IIa trial.

Conditions

Short Bowel Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in the Weekly Frequency of Bowel Movements Measured Between Baseline and the Second Week of Treatment

  Change in the weekly frequency of bowel movements measured between baseline and the second week of treatment. Baseline is defined as the second week of screening for treatment period 1 and second week of washout for treatment period 2.

  Baseline and Week 2 of treatment (Days 8 to 14, and Days 36 to 42)

Secondary Outcomes (3)

• Total Number of Bowel Movements for the Whole 2-week Treatment Period

  Days 1 to 14 and Days 29 to 42

• Mean Daily Stool Form Score According to the BSFS (Bristol Stool Form Scale), Measured During the Second Week of Treatment

  Days 8 to 14, and Days 36 to 42

• Mean Daily Dose of Loperamide in mg, if Used, During the Second Week of Treatment

  Days 8 to 14, and Days 36 to 42

Study Arms (2)

"Low" Dose ECC Regimen

EXPERIMENTAL

ECC at the 1.7 g daily dose, administered BID (twice daily) as 2 capsules of ECC, plus 3 capsules of placebo, at least 30 minutes before breakfast and 2 capsules of ECC, plus 3 capsules of placebo at least 30 minutes before evening meal.

Drug: Enteric-Coated Cholestyramine (ECC) Capsule; Drug: Placebo

"High" Dose ECC Regimen

EXPERIMENTAL

ECC at the 4.25 g daily dose, administered BID (twice daily) as 5 capsules of ECC at least 30 minutes before breakfast and 5 capsules of ECC at least 30 minutes before evening meal.

Drug: Enteric-Coated Cholestyramine (ECC) Capsule

Interventions

Enteric-Coated Cholestyramine (ECC) Capsule DRUG

Enteric-Coated Delayed Release Cholestyramine Capsules

"High" Dose ECC Regimen; "Low" Dose ECC Regimen

Placebo DRUG

Enteric-Coated Delayed Release Placebo Capsules

"Low" Dose ECC Regimen

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult, ambulatory male and female subjects
• Provision of signed and dated informed consent form (ICF)
• Age ≥ 18 years and ≤ 80 years
• Stable SBS of:
• Non-surgical origin; OR
• Surgical origin where the last surgical ileal resection was performed at least 6 months prior to enrolment
• Partial, Home Parenteral Nutrition and/or parenteral fluids are allowed, at a maximum frequency of 6 times a week throughout the trial, as long as the regimen has been stable for at least 2 weeks prior to screening and is expected to remain unchanged during the study
• At least 50 % of the colon being intact
• Intact duodenum
• BMI ≥ 18
• Presence of stable chronic diarrhea for at least 3 months prior to enrolment as evidenced by medical history
• Presence of stable chronic diarrhea during the 2-week screening diary period before randomization, as evidenced by completion of a screening diary demonstrating:
• Mean daily production of at least 3 soft or watery stools (BSFS scores 6 or 7); or
• More than 3 bowel movements per day on average with \>25% of them being BSFS type 6 or 7
• Stated willingness and ability to comply with all study procedures, including daily recording of bowel movements and BSFS in the patient diaries, and availability for the duration of the study

You may not qualify if:

• Patients with known or suspected intestinal strictures of clinical relevance as judged by the Investigator
• Active inflammatory bowel disease (IBD) or fistula during the screening period as judged by the Investigator
• Crohn's disease patients not being in clinical remission for the last 12 weeks prior to randomization
• Diarrhea caused by other causes than SBS
• Presence of clinically significant steatorrhea, requiring pancreatic enzymes supplementation
• Presence of complete biliary obstruction
• Presence of active cancer (except resected cutaneous basal or squamous cell carcinoma and except in situ cervical cancer) and/or need to receive chemotherapy or radiotherapy during the study
• History of allergic reaction to cholestyramine or any excipient of the investigational drug product or placebo, or packaging components
• Females who are lactating at screening
• Females who are pregnant according to the pregnancy test at screening or prior to the first study treatment administration
• Significant history (at least 3 consecutive months in the year prior to Screening) of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Subjects who took an Investigational Product (IP) in the 30 days prior to the first study drug administration
• Any other clinically significant condition that is considered by the principal investigator as being susceptible to put the patient at greater safety risk, influence response to study product, or interfere with study assessments.

Sponsors & Collaborators

• Pharmascience Inc.: lead

Study Sites (3)

Wojewódzki Specjalistyczny Szpital im. M. Pirogowa w Łodzi

Lodz, Poland

Location

Solumed Centrum Medyczne

Poznan, Poland

Location

Szpital Wielospecjalistyczny im. Stanleya Dudricka

Skawina, Poland

Location

MeSH Terms

Conditions

Short Bowel Syndrome

Interventions

Capsules

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed and abbreviated statistical analyses.

Results Point of Contact

• Title: Clinical Study Manager
• Organization: Pharmascience Inc.

researchsupport@pharmascience.com

514-340-9800

Study Officials

• Marek Kunecki, MD, PhD

  Wojewódzki Specjalistyczny Szpital im. M. Pirogowa w Łodzi

  PRINCIPAL INVESTIGATOR

• Konrad Matysiak, MD, PhD

  Solumed Centrum Medyczne

  PRINCIPAL INVESTIGATOR

• Kinga Szczepanek, MD

  Szpital Wielospecjalistyczny im. Stanleya Dudricka

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study will be fully blinded, using the double dummy technique (combination of active ECC capsules and matching placebo in the low dose treatment arm).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple-center, randomized, double-blind, double dummy, 2-period, 2-sequence cross-over design

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: August 6, 2019
• Study Start: October 15, 2019
• Primary Completion: December 22, 2021
• Study Completion: December 22, 2021
• Last Updated: July 19, 2022
• Results First Posted: July 19, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3)