Functional Constipation: Linaclotide versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, with Functional Constipation (FC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

29 Feb 2024 → 2 Sep 2025

Decision date (initial)

2023-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2022-501946-31-00

ClinicalTrials.gov

NCT05652205

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Part 1: to evaluate the safety and efficacy of 12 weeks of linaclotide therapy in comparison with placebo in pediatric subjects aged 2 to 5 years who meet modified Rome IV criteria for childhood FC.
Part 2: to assess the long-term safety of linaclotide administered to subjects with pediatric FC who have completed study intervention in Part 1 of this study or completed Study LIN-MD-67.

Conditions and MedDRA coding

Functional Constipation

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000927-PIP01-10

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Subjects must be ages 24 months to 5 years and 11 months (inclusive) at the time the caregiver/parent/guardian/LAR has provided signed consent in alignment with local requirements.
2. Subject does not have any condition or clinically significant findings on a physical examination, vital sign assessment, ECG, or clinical laboratory tests at Screening (Visit 1), 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 subject from performing any protocol assessments, or could confound study assessments.
3. Subject meets modified Rome IV criteria for FC: For at least 1 month before Screening (Visit 1), the subject 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.
4. Caregiver/parent/guardian/LAR is willing to discontinue any laxatives used before the Preintervention Visit (Visit 2) in favor of the protocol-permitted rescue medicine.
5. Based on the eDiary, the subject has an average ≤ 2 SBMs per week during the 14 days before the randomization day and up to the randomization (including the 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.

Exclusion criteria 8

1. Subjects with conditions that could interfere with drug absorption including, but not limited to, short bowel syndrome.
2. Subjects with history of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
3. Subjects with history of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.
4. Subjects with condition of unexplained and clinically significant alarm symptoms (lower gastrointestinal [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.
5. Subjects with history of known or suspected mechanical bowel obstruction or pseudo-obstruction.
6. Subject did not use a protocol-specified prohibited medicine before the start of the Preintervention Period or failed to meet the stable-dose requirements of certain medications.
7. Subject must not have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently enrolled in another clinical study or was previously enrolled in this study.
8. Subject must not have any planned or ongoing toilet training at any time in Part 1. Subjects may start toilet training at any time during Part 2. Toilet training is defined as the process of training a child to recognize their body signals for the need to urinate and/or have a bowel movement, to control the urination and/or bowel movement and to use the toilet. Children who are fully toilet trained or who have not yet started the process are eligible to participate.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in 12-week SBM frequency rate (SBMs/week) observed by the primary caregiver during the double-blind study intervention period.

Secondary endpoints 3

1. Change from baseline in 12-week stool consistency observed by the primary caregiver during the double-blind study intervention period
2. Change from baseline in 12-week straining observed by the primary caregiver during the double-blind study intervention period
3. Change from baseline in 12-week proportion of days with fecal incontinence during the double-blind study intervention period (for subjects who have acquired toileting skills during daytime and nighttime or acquired toileting skills during daytime only)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 6

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications