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Linaclotide Safety and Efficacy in 2 to 5-Year-Old Participants With Functional Constipation

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: NCT04110145
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : October 1, 2020
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Allergan

Brief Summary:
The purpose of this study is to evaluate the dose response, safety, and efficacy of linaclotide when compared with placebo in pediatric participants, 2 to 5 years of age, with Functional Constipation.

Condition or disease Intervention/treatment Phase
Functional Constipation Drug: Linaclotide Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: There are 3 cohorts with ascending doses and an additional final cohort to repeat the highest dose determined to be safe
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Sequential, Ascending, Multidose Study to Evaluate the Safety and Efficacy of Linaclotide in Pediatric Participants (Age 2 to 5 Years) With Functional Constipation
Actual Study Start Date : October 14, 2019
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

Arm Intervention/treatment
Cohort 1
linaclotide 18 μg or matching placebo once daily for 4-week Study Intervention Period.
Drug: Linaclotide
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Drug: Placebo
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Cohort 2
linaclotide 36 μg or matching placebo once daily for 4-week Study Intervention Period
Drug: Linaclotide
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Drug: Placebo
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Cohort 3
linaclotide 72 μg or matching placebo once daily for 4-week Study Intervention Period.
Drug: Linaclotide
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Drug: Placebo
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Final Cohort
linaclotide at the highest dose tested/determined to be safe or matching placebo once daily for 4-week Study Intervention Period
Drug: Linaclotide
Single dose, once daily at approximately the same time each day, 30 minutes before any meal

Drug: Placebo
Single dose, once daily at approximately the same time each day, 30 minutes before any meal




Primary Outcome Measures :
  1. Change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate (SBMs/week) during the Study Intervention Period of each cohort [ Time Frame: 29 Days ]
  2. Change from baseline in 4-week stool consistency reported by the caregiver during the Study Intervention Period of each cohort [ Time Frame: 29 Days ]
  3. Change from baseline in 4-week straining reported by the caregiver during the Study Intervention Period of each cohort [ Time Frame: 29 Days ]
  4. Proportion of days with fecal incontinence during the Study Intervention Period (for participants who have acquired toileting skills during the daytime and nighttime or acquired toileting skills during daytime only) within each cohort [ Time Frame: 29 Days ]


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.


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Ages Eligible for Study:   2 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant weighs ≥ 10 kg at the time the parent/guardian/legally authorized representative (LAR) has provided signed consent
  • Participant meets modified Rome III criteria for FC: For at least 2 months before Screening (Visit 1) (for participants aged ≥ 4 years old), or for at least 1 month before Screening (Visit 1) (for participants aged < 4 years old), the participant has had 2 or fewer defecations (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) per week.

In addition, at least once per week, participant must meet 1 or more of the following:

  1. History of retentive posturing or excessive volitional stool retention
  2. History of painful or hard bowel movements (BMs)
  3. Presence of a large fecal mass in the rectum
  4. History of large diameter stools that may obstruct the toilet
  5. At least one episode of fecal incontinence per week after the acquisition of toileting skills

    • Participant is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol- permitted rescue medicine
    • Parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures
    • Caregiver who will be completing the eDiary is able to read and/or understand the assessments in the eDiary device and must undergo training

Exclusion Criteria:

  • For participants aged ≥ 4 years old: Participant meets Rome III criteria for Child/Adolescent IBS: At least once per week for at least 2 months before Screening (Visit 1), the participant has experienced abdominal discomfort (an uncomfortable sensation not described as pain) or pain associated with 2 or more of the following at least 25% of the time:

    1. Improvement with defecation
    2. Onset associated with a change in frequency of stool
    3. Onset associated with a change in form (appearance) of stool
  • Participant has required manual dis-impaction any time prior to randomization or dis-impaction during in-patient hospitalization within 1 year prior to randomization
  • Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia, or any unexplained anemia, or weight loss) and systemic signs of infection or colitis, or any neoplastic process
  • Participant has had surgery that meets any of the following criteria:

    1. Surgery to remove a segment of the GI tract at any time before Screening (Visit 1)
    2. Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit
    3. An appendectomy or cholecystectomy during the 60 days before Screening (Visit 1)
    4. Other major surgery during the 30 days before Screening (Visit 1)
  • Participant has a mechanical bowel obstruction or pseudo-obstruction.
  • Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class
  • Participant has any of the following conditions:

    1. Celiac disease, or positive serological test for celiac disease or the condition is suspected but has not been ruled out by endoscopic biopsy
    2. Cystic fibrosis
    3. Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to Screening (Visit 1)
    4. Down's syndrome or any other chromosomal disorder
    5. Active anal fissure (ie, participant reports having streaks of blood on the stool or on toilet paper and/or pain/crying with bowel movement within 2 weeks prior to Screening). (Note: Anal fissures that have resolved at least 2 weeks prior to screening would not be exclusionary.) However, if in the investigator's opinion, an anal fissure(s) may be the primary cause of participant's modified Rome III FC criteria, the participant would not be eligible to participate in the study.
    6. Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displaced anus)
    7. Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceral myopathies, visceral neuropathies)
    8. Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
    9. Lead toxicity, hypercalcemia
    10. Neurodevelopmental disabilities (early-onset, chronic disorders that share the essential feature of a predominant disturbance in the acquisition of cognitive, motor, language, or social skills, which has a significant and continuing impact on the developmental progress of an individual) producing a cognitive delay that precludes comprehension and completion of the daily eDiary or other study-related questionnaires (Note: Participants are excluded if the person who will be completing the daily eDiary or other study-related questionnaires meets this criterion.)
    11. Inflammatory bowel disease
    12. Childhood functional abdominal pain syndrome
    13. Childhood functional abdominal pain
    14. Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study
    15. Lactose intolerance that is associated with symptoms which could confound the assessments in this study
    16. History of cancer other than treated basal cell carcinoma of the skin. (Note:

Participants with a history of cancer are allowed provided that the malignancy has been in a complete remission before the Randomization Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment.)

  • Participant received a study intervention during the 30 days before Screening (Visit 1) or is planning to receive study intervention (other than that administered during this study)
  • Participant's parent/guardian/LAR or caregiver has been directly or indirectly involved in the conduct and administration of this study as an investigator, study coordinator, or other study staff member. In addition, any participant, parent/guardian/LAR or caregiver who has a first-degree family member, significant other, or relative residing with him/her directly or indirectly who is involved in this study
  • For participants aged ≥ 4 years old: Participant has a history of non-retentive fecal incontinence

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): NCT04110145


Contacts
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Contact: Clinical Trials Registry Team 877-277-8566 IR-CTRegistration@Allergan.com

Locations
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Sponsors and Collaborators
Allergan
Ironwood Pharmaceuticals, Inc.
Investigators
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Study Director: Anna Muslin Allergan
Additional Information:
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Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT04110145    
Other Study ID Numbers: LIN-MD-67
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: October 1, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: After having received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published.
Access Criteria: To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes.
URL: http://www.allerganclinicaltrials.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Allergan:
Functional constipation in children
LINZESS
Additional relevant MeSH terms:
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Constipation
Signs and Symptoms, Digestive
Linaclotide
Guanylyl Cyclase C Agonists
Enzyme Activators
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents