Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    LIN_MD_64 | IBS - Irritable Bowel Syndrome

Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)

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: NCT04026113
Recruitment Status : Recruiting
First Posted : July 19, 2019
Last Update Posted : July 1, 2022
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Allergan

Brief Summary:
The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (72 μg daily) in comparison with placebo in pediatric participants, 6 to 17 years of age, who fulfill modified Rome III Criteria for Child/Adolescent Functional Constipation (FC). The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (145 μg or 290 μg daily) in pediatric participants, 7 to 17 years of age, who fulfill the Rome III criteria for child/adolescent Irritable Bowel Syndrome (IBS) and modified Rome III criteria for child/adolescent Functional Constipation (FC).

Condition or disease Intervention/treatment Phase
Functional Constipation Irritable Bowel Syndrome With Constipation Drug: Linaclotide 72 μg (FC Participants) Drug: Placebo (FC Participants) Drug: Linaclotide 145 μg (IBS-C Participants) Drug: Linaclotide 290 μg (IBS-C Participants) Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 426 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide in Pediatric Participants, Ages 6 to 17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) and of Linaclotide Versus Placebo in Pediatric Participants With Functional Constipation (FC)
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : July 11, 2023
Estimated Study Completion Date : April 5, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

Arm Intervention/treatment
Experimental: Linaclotide 72 μg
FC Participants: Single dose, once daily at approximately the same time each day, 30 minutes before any meal
Drug: Linaclotide 72 μg (FC Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)

Experimental: Placebo
FC Participants: Single dose, once daily at approximately the same time each day, 30 minutes before any meal
Drug: Placebo (FC Participants)
Matching placebo

Experimental: Linaclotide 145 μg
IBS-C Participants: Single dose, once daily at approximately the same time each day, 30 minutes before any meal
Drug: Linaclotide 145 μg (IBS-C Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)

Experimental: Linaclotide 290 μg
IBS-C Participants: Single dose, once daily at approximately the same time each day, 30 minutes before any meal
Drug: Linaclotide 290 μg (IBS-C Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)




Primary Outcome Measures :
  1. Functional Constipation (FC) Participants: Change from baseline in 12-week SBM (spontaneous bowel movement) frequency rate (SBMs/week) during the study intervention period [ Time Frame: 12 Weeks ]
    An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) will be measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.

  2. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks APS (abdominal pain and SBM) + 2 responder [ Time Frame: 12 Weeks ]
    A 6/12 weeks APS + 2 responder is a participant that meets the weekly APS + 2 responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly APS +2 responder is a participant who has an increase of at least 2 in the SBM weekly rate from baseline, AND a decrease of at least 30% in the mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain and BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.


Secondary Outcome Measures :
  1. Functional Constipation (FC) Participants: Change from baseline in 12-week stool consistency during the study intervention period [ Time Frame: 12 Weeks ]
    Stool consistency will be measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery A participant’s p-BSFS score for the study intervention period will be the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.

  2. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week SBM frequency rate (SBMs/week) during the study intervention period [ Time Frame: 12 Weeks ]
    An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) will be measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.

  3. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week abdominal pain during the study intervention period [ Time Frame: 12 Weeks ]
    Assessments of abdominal pain will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.

  4. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week stool consistency during the study intervention period [ Time Frame: 12 Weeks ]
    Stool consistency will be measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery A participant’s p-BSFS score for the study intervention period will be the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.

  5. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks SBM + 2 responder [ Time Frame: 12 Weeks ]
    Assessments of BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.

  6. Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks abdominal pain responder [ Time Frame: 12 Weeks ]
    Assessments of abdominal pain will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.



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:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female participants must be ages 6 to 17 years (FC participants) or ages 7 to 17 years (IBS-C participants) (inclusive) at the time the participant provides assent for the study and parent/guardian/legally authorized representative (LAR) has provided signed consent;
  • Participant weighs ≥18 kg at the time the participant provides assent and the parent/guardian/LAR has provided signed consent;
  • Participants who meet the modified Rome III criteria for Child/Adolescent FC. For at least 2 months before the Screening Visit, 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) in the toilet per week.

In addition, participant meets one or more of the following criteria at least once per week for at least 2 months before the screening visit:

a. History of retentive posturing or excessive volitional stool retention; b. History of painful or hard BMs; c. History of large diameter stools that may obstruct the toilet; d. Presence of a large fecal mass in the rectum; e. At least 1 episode of fecal incontinence per week

  • For IBS-C participants only: Participant meets Rome III criteria for child/adolescent IBS: At least once per week for at least 2 months before the Screening Visit, the participant 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;
  • For IBS-C participants only: Participant has an average daytime abdominal pain score of ≥ 1 (at least "a tiny bit") during the 14 days before Visit 3;
  • Participant is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol- permitted rescue medicine;
  • Participant has an average of fewer than 3 SBMs per week during the 14 days before the randomization day and up to the randomization (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day). An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM;
  • Participant or parent/guardian/LAR or caregiver is compliant with eDiary requirements by completing both the morning and evening assessments for 10 out of the 14 days immediately preceding the Randomization Visit;
  • Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Randomization Visit prior to dosing;
  • Female participants who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception;
  • Participant must provide written or verbal informed assent and the parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures;
  • Participant is able to read and/or understand the assessments in the eDiary device. If the participant is 6 to 11 years of age (FC participants) or 7 to 11 years of age (IBS-C participants) and does not meet this criterion, the interviewer-administered version of the eDiary must be used and the parent/guardian/LAR or caregiver who will be administering the interviewer-administered version of the eDiary must undergo training;
  • Participant must have acquired toilet training skills.

Exclusion Criteria:

  • For FC participants only: Participant meets Rome III criteria for Child/Adolescent IBS: At least once per week for at least 2 months before the Screening Visit, 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 reports having more than 1 loose, mushy stool (eDiary-recorded stool consistency of 6 on the Pediatric Bristol Stool Form Scale [p-BSFS]) or any watery stool (eDiary-recorded stool consistency of 7 on the p-BSFS) with any SBM that occurred in the absence of laxative use on the calendar day of the BM or the calendar day before the BM during the 14 days before the randomization day and up to the randomization (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day);
  • Participant has a history of non-retentive fecal incontinence;
  • Participant has (a) fecal impaction at Visit 2 after failing outpatient clean-out during the Screening Period or (b) fecal impaction at Visit 3;
  • Participant has required manual disimpaction any time 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 clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), or clinical laboratory test as determined by the investigator based on consideration of whether the finding could represent a safety concern or a condition that would be exclusionary, could prevent the participant from performing any protocol assessments, or could confound study assessments;
  • Participant has a history of drug or alcohol abuse;
  • Participant has any of the following conditions:

    1. Celiac disease, or positive serological test for celiac disease and the condition 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 the Screening Visit;
    4. Down's syndrome or any other chromosomal disorder;
    5. Active anal fissure (Note: History of anal fissure is not an exclusion);
    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 (Electronic handheld device) 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 abdominal pain or discomfort and 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 for at least 5 years before the Randomization Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment);
    17. History of diabetic neuropathy.
  • Participant has an acute or chronic condition that, in the investigator's opinion, would limit the participants' ability to complete or participate in this clinical study;
  • Participant has a known or suspected mechanical bowel obstruction or pseudoobstruction;
  • Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class.
  • Participant has had surgery that meets any of the following criteria:

    1. Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit;
    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 the Screening Visit;
    4. Other major surgery during the 30 days before the Screening Visit;
  • Participant used a protocol-specified prohibited medicine before the start of the Preintervention Period or failed to meet the stable-dose requirements of certain medications;
  • Participant used rescue medication on the calendar day before the Randomization Visit and on the day of the Randomization Visit until randomized;
  • Participant received a study intervention during the 30 days before the Screening Visit or is planning to receive a study intervention (other than that administered during this study);
  • Participant has been randomized into any clinical study in which linaclotide was a study intervention.
  • The participant has a condition or is in a situation; which, in the investigator's opinion, may put the participant at significant risk, may confound the study results ,or may interfere significantly with the participant's participation in the study;
  • Participants who have positive urine drug screen results for cocaine, barbiturates, opiates, or cannabinoids will be excluded from study participation;
  • Female participants who are currently pregnant or nursing, or plan to become pregnant or nurse during the clinical 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.

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): NCT04026113


Contacts
Layout table for location contacts
Contact: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com

Locations
Show Show 127 study locations
Sponsors and Collaborators
Allergan
Ironwood Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: ALLERGAN INC. Allergan
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT04026113    
Other Study ID Numbers: LIN-MD-64
2019-001500-38 ( EudraCT Number )
First Posted: July 19, 2019    Key Record Dates
Last Update Posted: July 1, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
URL: https://vivli.org/ourmember/abbvie/

Layout table for additional information
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 Allergan:
Functional constipation in children
Irritable Bowel Syndrome with Constipation
LINZESS
Additional relevant MeSH terms:
Layout table for MeSH terms
Irritable Bowel Syndrome
Syndrome
Intestinal Diseases
Constipation
Disease
Pathologic Processes
Signs and Symptoms, Digestive
Colonic Diseases, Functional
Colonic Diseases
Gastrointestinal Diseases
Digestive System Diseases
Linaclotide
Guanylyl Cyclase C Agonists
Enzyme Activators
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents