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

NCT ID: NCT04046328

Last Updated: 2022-07-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-15
• Study Completion Date: 2021-12-22

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.

Detailed Description

A new Enteric-Coated Cholestyramine (ECC) capsule has been developed to manage diarrhea associated with Short Bowel Syndrome (SBS). SBS is usually caused by the significant resection or loss of function of the ileum, leading to reduced reabsorption of bile acids and subsequent osmotic diarrhea. The new ECC formulation could release cholestyramine in the remaining segment of the small intestine in SBS patients, delivering and binding bile acids before they induce diarrhea in the colon. The proposed advantages of this formulation are: a) to prevent drug-drug interactions in the proximal GI tract, b) to preserve the fat digestive properties of bile acids in the duodenum and 3) to offer a more palatable dosage form to patients. Moreover, since distal delivery of cholestyramine is expected to be more effective in diarrhea prevention/reduction in SBS, lower doses than the ones used with non-enteric coated cholestyramine may be sufficient. Two doses of ECC will be studied for efficacy, safety and tolerability in well-defined non fully-colectomized, adult SBS patients suffering from diarrhea.

Conditions

Short Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

"Low" Dose ECC Regimen

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.

Group Type: EXPERIMENTAL

Enteric-Coated Cholestyramine (ECC) Capsule

Intervention Type: DRUG

Enteric-Coated Delayed Release Cholestyramine Capsules

Placebo

Intervention Type: DRUG

Enteric-Coated Delayed Release Placebo Capsules

"High" Dose ECC Regimen

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.

Group Type: EXPERIMENTAL

Enteric-Coated Cholestyramine (ECC) Capsule

Intervention Type: DRUG

Enteric-Coated Delayed Release Cholestyramine Capsules

Interventions

Enteric-Coated Cholestyramine (ECC) Capsule

Enteric-Coated Delayed Release Cholestyramine Capsules

Intervention Type: DRUG

Placebo

Enteric-Coated Delayed Release Placebo Capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult, ambulatory male and female subjects

2. Provision of signed and dated informed consent form (ICF)

3. Age ≥ 18 years and ≤ 80 years

4. Stable SBS of:

1. Non-surgical origin; OR

2. Surgical origin where the last surgical ileal resection was performed at least 6 months prior to enrolment

5. 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

6. At least 50 % of the colon being intact

7. Intact duodenum

8. BMI ≥ 18

9. Presence of stable chronic diarrhea for at least 3 months prior to enrolment as evidenced by medical history

10. Presence of stable chronic diarrhea during the 2-week screening diary period before randomization, as evidenced by completion of a screening diary demonstrating:

1. Mean daily production of at least 3 soft or watery stools (BSFS scores 6 or 7); or

2. More than 3 bowel movements per day on average with >25% of them being BSFS type 6 or 7

11. 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

12. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by the investigator

13. Female subjects must meet one of the following criteria:

a) Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 30 days prior to the first study treatment administration through to at least 30 days after the last dose of the study treatment. An acceptable method of contraception includes one of the following:

1. Abstinence from heterosexual intercourse

2. Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)

3. Intrauterine device (with or without hormones)

4. Condom with spermicide

b) Participants of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy or bilateral oophorectomy) or is in a menopausal state (i.e. at least 1 year without menses prior to the first study drug administration) are eligible

Exclusion Criteria

1. Patients with known or suspected intestinal strictures of clinical relevance as judged by the Investigator

2. Active inflammatory bowel disease (IBD) or fistula during the screening period as judged by the Investigator

3. Crohn's disease patients not being in clinical remission for the last 12 weeks prior to randomization

4. Diarrhea caused by other causes than SBS

5. Presence of clinically significant steatorrhea, requiring pancreatic enzymes supplementation

6. Presence of complete biliary obstruction

7. 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

8. History of allergic reaction to cholestyramine or any excipient of the investigational drug product or placebo, or packaging components

9. Females who are lactating at screening

10. Females who are pregnant according to the pregnancy test at screening or prior to the first study treatment administration

11. 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)

12. Subjects who took an Investigational Product (IP) in the 30 days prior to the first study drug administration

13. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmascience Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marek Kunecki, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Wojewódzki Specjalistyczny Szpital im. M. Pirogowa w Łodzi

Konrad Matysiak, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Solumed Centrum Medyczne

Kinga Szczepanek, MD

Role: PRINCIPAL_INVESTIGATOR

Szpital Wielospecjalistyczny im. Stanleya Dudricka

Locations

Wojewódzki Specjalistyczny Szpital im. M. Pirogowa w Łodzi

Lodz, , Poland

Solumed Centrum Medyczne

Poznan, , Poland

Szpital Wielospecjalistyczny im. Stanleya Dudricka

Skawina, , Poland

Countries

Poland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-004419-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PMS-2018-002

Identifier Type: -

Identifier Source: org_study_id