A Study to Assess Adverse Events and Change in Symptoms W... | NCT05652205

ID	Type	Description	Link
2022-501946-31-00	Other Identifier	EU CT

Status Module

Name	Class
Ironwood Pharmaceuticals, Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Placebo for Linaclotide	Placebo Comparator	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.	Drug: Placebo for Linaclotide
Part 1: Linaclotide	Experimental	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.	Drug: Linaclotide
Part 2: Linaclotide	Experimental	Participants who received 72 µg linaclotide or placebo in Part 1 of this study or who entered Part 2 of this study from Study LIN-MD-67 (NCT04110145) were assigned to receive open-label linaclotide 72 µg orally once daily (QD) for 24 weeks at the start of Part 2.	Drug: Linaclotide

Name	Type	Description	Arm Group Labels	Other Names
Placebo for Linaclotide	Drug	Capsule; oral	Part 1: Placebo for Linaclotide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in 12-week Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) Observed by the Primary Caregiver During the Double-blind Study Intervention Period	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. The caregiver/parent/guardian/legally authorized representative (LAR) will complete the electronic diary (eDiary), providing data for the SBM frequency rate up to the last dose date equivalent to the 12-week SBM frequency rate. Baseline values for efficacy endpoints related to daily eDiary responses were derived from the eDiary in the preintervention period, specifically the time period from 14 days before randomization and up to the time of randomization.	Baseline to Week 12
Number of Participants With Treatment-Emergent Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient/clinical investigation subject administered a pharmaceutical product which doesn't necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.	From the time of study drug administration until 30 days or 5 half-lives after the last dose, up to 126 days in Period 1 and 226 days in Period 2

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in 12-week Stool Consistency Observed by the Primary Caregiver During the Double-blind Study Intervention Period	The caregiver/parent/guardian/legally authorized representative (LAR) rated and recorded in an eDiary the consistency of the stool for each BM using the Bristol Stool Form 7-point scale in which 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; and 7=Watery, no solid pieces, entirely liquid. A response of "I don't know" was considered as a missing score. Lower scores indicate firmer stool consistency. A subject's stool consistency score for the study intervention period is the average of the non-missing BSFS scores for the primary caregiver-observed SBMs during that specific period.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Caregiver/parent/guardian/legally authorized representative (LAR) is willing and able to comply with procedures required in this protocol, prior to the initiation of any screening or study-specific procedures. In addition, the caregiver/parent/guardian/LAR who will be completing the electronic diary (eDiary) must be able to read and understand the assessments in the eDiary device and undergo training.
Participant meets modified Rome IV criteria for FC: For at least 1 month before Screening (Visit 1), 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:
- History of retentive posturing or excessive volitional stool retention.
- History of painful or hard bowel movements (BMs).
- Presence of a large fecal mass in the rectum.
- History of large diameter stools.
- At least 1 episode of fecal incontinence per week after the acquisition of toileting skills, if applicable.

Exclusion Criteria:

Participant history of:
- Celiac disease, or positive serological test for celiac disease or the condition is suspected but has not been ruled out by endoscopic biopsy
- Cystic fibrosis
- 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)
- Down's syndrome or any other chromosomal disorder
- Active anal fissure (i.e., participant reports having streaks of blood on the stool or on toilet paper and/or pain/crying with BM 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 IV FC criteria, the participant would not be eligible to participate in the study.
- Anatomic malformations (e.g., imperforate anus, anal stenosis, anterior displaced anus)
- Intestinal nerve or muscle disorders (e.g., Hirschprung disease, visceral myopathies, visceral neuropathies)
- Neuropathic conditions (e.g., spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
- Lead toxicity, hypercalcemia
- Inflammatory bowel disease
- Childhood functional abdominal pain syndrome
- Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study
- Lactose intolerance that is associated with symptoms which could confound the assessments in this study
- History of cancer. (Note: participants with a history of cancer are allowed provided that the malignancy has been in a complete remission before Randomization (Visit 2). A complete remission is defined as the disappearance of all signs of cancer in response to treatment.)
Has conditions that could interfere with drug absorption including but not limited to short bowel syndrome.

Name	Affiliation	Role
ABBVIE INC.	AbbVie	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
G & L Research, LLC /ID# 250658		Foley	Alabama	36535	United States
Velocity Clinical Research - Phoenix /ID# 266280

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
FG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 20, 2025	Mar 23, 2026

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in 12-week Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) Observed by the Primary Caregiver During the Double-blind Study Intervention Period

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. The caregiver/parent/guardian/legally authorized representative (LAR) will complete the electronic diary (eDiary), providing data for the SBM frequency rate up to the last dose date equivalent to the 12-week SBM frequency rate.

Baseline values for efficacy endpoints related to daily eDiary responses were derived from the eDiary in the preintervention period, specifically the time period from 14 days before randomization and up to the time of randomization.

ITT1 population- all randomized participants who received at least one dose of double-blinded study drug in Part 1

Posted

Least Squares Mean

Standard Error

SBMs/week

Baseline to Week 12

ID	Title	Description
OG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
OG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Units	Counts
Participants	OG00061 OG00162

Title

Denominators

Categories

Title	Measurements
	OG0001.418± 0.2197 OG0011.738± 0.2188

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Linaclotide vs Placebo Missing data were imputed, assuming Missing Not at Random (MNAR). A postbaseline week value was considered missing if a subject had less than 4 completed diary days in that week.	Mixed Effect Model Repeated Measurement		=0.2929		LS Mean Difference	0.319	Standard Error of the Mean	0.3037	2-Sided	95	-0.2758	0.9146			Difference = Linaclotide - Placebo		Superiority	Mixed effect model for repeated measures (MMRM) used with treatment, week, age group, treatment-by-week interaction term as factors and Baseline value as a covariate. Within/between group estimates are average of Least Squares estimates of the week values for the corresponding treatment using estimate statement from MMRM model. Within/between group estimates are combined based on multiple imputed data. Associated 95% CIs and p-values are based on combined between group estimates.

Primary

Number of Participants With Treatment-Emergent Adverse Events

An adverse event (AE) is defined as any untoward medical occurrence in a patient/clinical investigation subject administered a pharmaceutical product which doesn't necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

All randomized participants who received ≥ 1 dose of study drug in Parts 1 (SA1) or 2 (SA2)

Posted

Count of Participants

Participants

From the time of study drug administration until 30 days or 5 half-lives after the last dose, up to 126 days in Period 1 and 226 days in Period 2

ID	Title	Description
OG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
OG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Secondary

Change From Baseline in 12-week Stool Consistency Observed by the Primary Caregiver During the Double-blind Study Intervention Period

The caregiver/parent/guardian/legally authorized representative (LAR) rated and recorded in an eDiary the consistency of the stool for each BM using the Bristol Stool Form 7-point scale in which 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; and 7=Watery, no solid pieces, entirely liquid. A response of "I don't know" was considered as a missing score. Lower scores indicate firmer stool consistency. A subject's stool consistency score for the study intervention period is the average of the non-missing BSFS scores for the primary caregiver-observed SBMs during that specific period.

Participants with analysis values at both Baseline and postbaseline (including imputed values) during the specified time period

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
OG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Secondary

Change From Baseline in 12-week Straining Observed by the Primary Caregiver During the Double-blind Study Intervention Period

The caregiver/parent/guardian/LAR rated and recorded in an eDiary the amount of straining they observed when the child passed the BM using two 3-point rating scales:. 1) For the bowel movement #X you were with the child for, did he/she grunt like he/she was straining? 0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; I don't know. 2) For the bowel movement #X you were with the child for, did he/she make a face like he/she was straining? 0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; I don't know. "I don't know" was considered a missing response. Higher scores indicate more straining. The subject's straining score was the average of the nonmissing average straining scores for all the primary caregiver-observed SBMs during the specific period.

Participants with analysis values at both Baseline and postbaseline (including imputed values) during the specified time period

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
OG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Secondary

Change From Baseline in 12-week Proportion of Days With Fecal Incontinence During the Double-blind Study Intervention Period (for Those With Toileting Skills)

Caregivers of children who have acquired toileting skills for BMs were asked about their child's fecal incontinence episodes. Toileting skills were assessed as part of the first daily diary, modified daily diary, or clinic diary and responses were carried through to the completion of the study.

Participants who have acquired toileting skills with analysis values at both baseline and postbaseline (including imputed values) during the specified time period

Posted

Least Squares Mean

Standard Error

proportion of days

Baseline to Week 12

ID	Title	Description
OG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
OG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.	61	0	61	5	61
EG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.	62	0	62	6	62
EG002	Part 2: Linaclotide	Participants who received 72 µg linaclotide or placebo in Part 1 of this study or who entered Part 2 of this study from Study LIN-MD-67 (EudraCT 2019-002126-75) were assigned to receive open-label linaclotide 72 µg orally once daily (QD) for 24 weeks at the start of Part 2.	104	1	104	23	104

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DIARRHOEA	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected61 at risk EG0011 events1 affected62 at risk EG0024 events4 affected104 at risk
PYREXIA	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0012 events2 affected62 at risk EG0024 events3 affected104 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0010 events0 affected62 at risk EG0023 events3 affected104 at risk
EAR INFECTION	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0010 events0 affected62 at risk EG0025 events4 affected104 at risk
INFLUENZA	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0011 events1 affected62 at risk EG0025 events5 affected104 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected61 at risk EG0012 events2 affected62 at risk EG0023 events3 affected104 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0010 events0 affected62 at risk EG0023 events3 affected104 at risk
VIRAL UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected61 at risk EG0010 events0 affected62 at risk EG0025 events4 affected104 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected61 at risk EG0010 events0 affected62 at risk EG0021 events1 affected104 at risk

ID	Title	Description
BG000	Part 1: Placebo for Linaclotide	Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
BG001	Part 1: Linaclotide	Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.
BG002	Total	Total of all reporting groups