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A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04779320
Recruitment Status : Recruiting
First Posted : March 3, 2021
Last Update Posted : August 30, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:

Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, children and teenagers with moderate to severe Crohn's disease will be treated with vedolizumab.

The main aim of the study is to check if participants achieve remission after treatment with the vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no signs of inflammation.

Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive either a high dose or low dose of vedolizumab once every 8 weeks. They will receive the same dose every time.


Condition or disease Intervention/treatment Phase
Crohn's Disease (CD) Drug: Vedolizumab IV Phase 3

Detailed Description:

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active CD. The drug is tested and approved in adults in approximately 70 countries. Participants to be enrolled must have failed response to, lost response to, or been intolerant to at least 1 of the current standard of care (SOC) induction and maintenance therapies for CD including exclusive and/or partial enteral nutrition therapy, immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], methotrexate [MTX]), and tumor necrosis factor-alpha (TNF-α) antagonists.

The study will enroll approximately 120 patients.

During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline as:

  • Participants ≥30 kg, Vedolizumab 300 mg
  • Participants >15 to <30 kg, Vedolizumab 200 mg
  • Participants 10 to 15 kg, Vedolizumab 150 mg

At Week 14, participants who achieve clinical response will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to 2 double-blind dose groups (high dose and low dose), stratified by previous exposure/failure to TNF-α antagonists therapy or naive to TNF-α antagonists therapy, and by weight groups. Participants will receive vedolizumab IV infusions every 8 weeks (Q8W) up to Week 46 during the Maintenance Period as follows:

  • Participants ≥30 kg, Vedolizumab 300 mg (High dose)
  • Participants ≥30 kg, Vedolizumab 150 mg (Low dose)
  • Participants >15 to <30 kg, Vedolizumab 200 mg (High dose)
  • Participants >15 to <30 kg, Vedolizumab 100 mg (Low dose)
  • Participants 10 to 15 kg, Vedolizumab 150 mg (High dose)
  • Participants 10 to 15 kg, Vedolizumab 100 mg (Low dose)

The dose will remain blinded to the participant and study doctor during the study (unless there is an urgent medical need). All participants will be administered vedolizumab via IV infusion. In participants who demonstrate lack of maintenance of clinical response during the Maintenance Period the dose will be escalated in a blinded fashion to the high dose in their weight group based on the weight at the time of the worsening of disease. In addition one-time rescue therapy with corticosteroids is allowed.

This multi-center trial will be conducted worldwide. After the Week 54, participants may be eligible to participate in extension study. Participants who do not roll over in the extension study will undergo a safety visit 18 weeks after the last dose of vedolizumab followed by 2 years of long term follow-up (up to 104 weeks). During this period a safety survey by telephone will be performed every 6 months for 2 years after the last dose of study drug.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects With Moderately to Severely Active Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
Actual Study Start Date : April 30, 2022
Estimated Primary Completion Date : November 30, 2024
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Vedolizumab

Arm Intervention/treatment
Experimental: Induction Period: ≥30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of ≥30 kg will be included in this arm group.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Induction Period: >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of >15 to <30 kg will be included in this arm group.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Induction Period: 10 to 15 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, at Day 1, Weeks 2 and 6 in Induction Period. Participants with CD having Baseline weight of 10 to 15 kg will be included in this arm group.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: ≥30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once every 8 weeks (Q8W) from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 300 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: ≥30 kg: Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 150 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 200 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: >15 to <30 kg Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: 10 to 15 kg Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 150 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002

Experimental: Maintenance Period: 10 to 15 kg Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.
Drug: Vedolizumab IV
Vedolizumab IV
Other Names:
  • ENTYVIO
  • KYNTELES
  • MLN0002




Primary Outcome Measures :
  1. Percentage of Participants With Clinical Remission at Week 54 Based on Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤10 [ Time Frame: Week 54 ]
    Clinical remission is defined by PCDAI score ≤10. The PCDAI was specifically designed for use in children. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: hematocrit (HCT) (adjusted for age and sex), erythrocyte sedimentation rate (ESR), and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. A score of <10 will be consistent with inactive disease, 11 to 30 will indicate mild disease, and >30 will indicate moderate to severe disease.

  2. Percentage of Participants With Endoscopic Response at Week 54 Based on Simple Endoscopic Score for Crohn's Disease [SES-CD] Score [ Time Frame: Week 54 ]
    Endoscopic response is defined as at least a 50% reduction in SES-CD score from Baseline. The SES-CD evaluates 4 endoscopic variables (size of ulcers, ulcerated surface, affected surface and presence of narrowing) each rated from 0 (best) to 3 (worst). The score for each endoscopic variable is sum of values obtained for each of the five segments (ileum, right colon, transverse colon, left colon and rectum). The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56 , where higher scores indicate more severe disease.


Secondary Outcome Measures :
  1. Percentage of Participants with Clinical and Endoscopic Remission at Week 14 Based on Both PCDAI Score and SES-CD Score [ Time Frame: Week 14 ]
    Clinical and endoscopic remission is where participant achieves both clinical and endoscopic remission. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined by SES-CD score of ≤4 with at least a 2-point reduction from Baseline and no sub-score >1. PCDAI includes child-specific item: height velocity variable as well as three laboratory parameters: HCT, ESR, albumin level. PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. SES-CD evaluates 4 endoscopic variables (size of ulcers, ulcerated surface, affected surface and presence of narrowing). Score for each endoscopic variable is sum of values obtained for each segment. SES-CD total is sum of 4 endoscopic variable scores ranges from 0 to 56, where higher scores indicate more severe disease.

  2. Percentage of Participants with Clinical and Endoscopic Remission at Week 54 Based on Both PCDAI Score and SES-CD Score [ Time Frame: Week 54 ]
    Clinical and endoscopic remission is where participant achieves both clinical and endoscopic remission. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined by SES-CD score of ≤4 with at least a 2-point reduction from Baseline and no sub-score >1. PCDAI includes a child-specific item: height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. Score for each endoscopic variable is sum of values obtained for each segment. SES-CD total is sum of four endoscopic variable scores ranges from 0 to 56, where higher scores indicate more severe disease.

  3. Percentage of Participants with Sustained Clinical and Endoscopic Remission at Week 54 [ Time Frame: Week 54 ]
    Sustained clinical and endoscopic remission is where a participant achieved clinical and endoscopic remission based on PCDAI and SES-CD scores at Weeks 14 and 54. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined as ≤4 with at least a 2-point reduction from Baseline and no sub-score >1 by SES-CD. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. The SES-CD evaluates four endoscopic variables (size of ulcers, ulcerated surface, affected surface and presence of narrowing). The score for each endoscopic variable is sum of values obtained for each segment. The SES-CD total is the sum of the four endoscopic variable scores ranges from 0 to 56, where higher scores indicate more severe disease.

  4. Percentage of Participants with Corticosteroid-free Remission at Week 54 Based on PCDAI Score [ Time Frame: Week 54 ]
    Corticosteroid-free clinical remission is where participants achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and has been off corticosteroids at least 12 weeks prior to and at Week 54. Clinical remission is defined by PCDAI score ≤10. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease.

  5. Percentage of Participants with Sustained Endoscopic Remission Based on SES-CD Score [ Time Frame: Week 54 ]
    Sustained endoscopic remission is where participants achieves endoscopic remission based on SES-CD ≤4 with at least a 2-point reduction from Baseline and no sub-score >1. The SES-CD evaluates 4 endoscopic variables (Size of ulcers, Ulcerated surface, Affected surface and Presence of narrowing). The score for each endoscopic variable is sum of values obtained for each segment. The SES-CD total is the sum of the four endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

  6. Percentage of Participants with Sustained Clinical Remission at Week 54 Based on PCDAI Score [ Time Frame: Week 54 ]
    Sustained Clinical Remission is where participants will achieve clinical remission based on PCDAI at Weeks 14 and 54. Clinical remission is defined by PCDAI score ≤10. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score will range from 0 to 100, with higher scores indicating more active disease.

  7. Serum Trough Concentrations of Vedolizumab Over Time [ Time Frame: Pre-dose and at multiple time points (up to 54 weeks) post-dose ]
  8. Percentage of Participants With Positive Antivedolizumab Antibodies [ Time Frame: Pre-dose (up to 54 weeks) ]
  9. Percentage of Participants With Positive Neutralizing Antivedolizumab Antibody Titers [ Time Frame: Pre-dose (up to 54 weeks) ]
  10. Sustained Clinical Response at Weeks 14 and 54 Based on PCDAI Score [ Time Frame: Weeks 14 and 54 ]
    Sustained clinical response is where a participant achieve clinical response based on PCDAI score ≤30 and reduction of the PCDAI by ≥15 points from Baseline. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score will range from 0 to 100, with higher scores indicating more active disease.

  11. Percentage of Participants with Clinical Remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 [ Time Frame: Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 ]
    Clinical remission is defined by PCDAI score < 10. The PCDAI was specifically designed for use in children. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT (adjusted for age and sex), ESR, and albumin level. The PCDAI score will range from 0 to 100, with higher scores indicating more active disease.

  12. Percentage of Participants with Clinical Response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 [ Time Frame: Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 ]
    Clinical Response is where participants achieves clinical response if PCDAI ≤30 with reduction in the PCDAI of ≥15 points from Baseline. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score will range from 0 to 100, with higher scores indicating more active disease.

  13. Percentage of Participants with at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AE of special interest (AESI) [ Time Frame: From first dose of study drug before each dose on dosing days through the Week 72 ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have causal relationship with this treatment. AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether it is considered related to drug. SAE is any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to congenital anomaly/birth defect and/or is important medical event. An AESI (serious or non-serious) is one of scientific and medical concern specific to compound or program, for which ongoing monitoring and rapid communication by investigator. AESIs include- opportunistic infection, such as progressive multifocal leukoencephalopathy (PML), liver injury, malignancies, infusion-related reactions, hypersensitivity.

  14. Change from Baseline in Weight [ Time Frame: Baseline up to Week 54 ]
    Change from in Baseline in weight will be calculated as: Weight at each study visit (up to Week 54) - Weight at Baseline.

  15. Change from Baseline in Linear Growth Z-score [ Time Frame: Baseline up to Week 54 ]
    Linear growth Z-score will be calculated as: Z-score = (observed value - median value of the reference population)/ standard deviation value of reference population.

  16. Percentage of Participants with Tanner Stage V at Week 54 [ Time Frame: Week 54 ]
    Tanner Stage is used to define physical measurements of sexual development based on external primary and secondary sex characteristics. Female and male participants are evaluated for breast development and genital development respectively and both genders for pubic hair distribution based on a 5-stage scale ranging from Stage I (prepubertal/preadolescent characteristics) to Stage V (mature or adult characteristics).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC).
  2. The participants weigh ≥10 kg at the time of screening and enrollment into the study.
  3. Participants with moderately to severely active Crohn's disease (CD) diagnosed at least 1 month before screening, defined by a Pediatric Crohn's Disease Activity Index (PCDAI) >30 and an simple endoscopic score for Crohn's Disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum).
  4. Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate [MTX]), and/or tumor necrosis factor (TNF)-α antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
  5. Participants with extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
  6. Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

Exclusion Criteria:

  1. Participants who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
  2. Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
  3. The participants had a clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 [COVID-19]) within 30 days prior to first dose of study drug.
  4. The participants has received any live vaccinations within 30 days prior to first dose.
  5. Participants who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
  6. Participants who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
  7. Participants with a current diagnosis of indeterminate colitis.
  8. Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
  9. Active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 30 days of screening or during the screening Period that is positive, defined as:

    • Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
    • A TB skin test reaction ≥5 mm.
  10. The participants has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection.
  11. The participants has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
  12. The participant has evidence of dysplasia or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
  13. Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
  14. Participants with positive Clostridium difficile stool test at screening visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04779320


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
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Sponsors and Collaborators
Takeda
Additional Information:
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04779320    
Other Study ID Numbers: MLN0002-3025
2020-004301-31 ( EudraCT Number )
jRCT2071210031 ( Registry Identifier: jRCT )
First Posted: March 3, 2021    Key Record Dates
Last Update Posted: August 30, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vedolizumab
Gastrointestinal Agents