A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age with Functional Constipation (FC).
- Trial ID
- 2022-501947-34-00
- Protocol
- M21-862
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2 study is to identify a tolerable, safe, and efficacious dose of **linaclotide** administered over a 4-week period in pediatric subjects aged 6 months to less than 2 years with **Functional Constipation (FC)**. This objective is clinically relevant as it aims to establish an appropriate dosing regimen for this age group, which is crucial for ensuring both the safety and therapeutic effectiveness of the treatment in managing FC. Additionally, the study seeks to evaluate the safety and efficacy of the identified dose of linaclotide over the same duration in the same pediatric population. This evaluation is essential for determining the potential of linaclotide as a treatment option for young children suffering from FC, a condition that can significantly impact quality of life and development.
Participants
The clinical trial involves a total of **15 participants** diagnosed with **Functional Constipation (FC)**. The study population consists of pediatric subjects aged **6 months to less than 2 years**, encompassing both male and female participants. The trial specifically targets a vulnerable population, as it includes very young children. Participants were selected based on specific criteria, including age and health status, such as having a weight-for-height/length ratio of at least the 3rd percentile for their age group. Additionally, subjects must meet the Rome IV criteria for FC, which includes symptoms like infrequent defecation, excessive stool retention, and painful bowel movements. The trial does not specify any particular lifestyle considerations such as diet or physical activity, focusing instead on the medical condition and age-related criteria for inclusion.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **efficacy** of **linaclotide** in pediatric subjects aged 6 months to less than 2 years with **functional constipation**. This is a Phase 2, randomized, double-blind, controlled study. The trial will involve a study intervention period of 4 weeks, during which participants will receive either linaclotide or a placebo. The primary objective is to identify a tolerable, safe, and efficacious dose of linaclotide for this age group. The trial is expected to conclude by December 19, 2024, with recruitment having started on September 11, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, weight-for-height ratio, and meeting the Rome IV criteria for functional constipation. Following successful screening, participants will be randomized to receive either the active drug or placebo. The study intervention period will include regular follow-up visits to monitor safety and efficacy outcomes, such as changes in spontaneous bowel movement frequency, stool consistency, and straining. The end-of-study visit will occur after the 4-week intervention period to collect final data and ensure participant safety.
The expected length of participant involvement is approximately 4 weeks, with additional time for screening and follow-up assessments. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent by the legally authorized representative, or failure to comply with study procedures. The trial will adhere to rigorous ethical standards, with informed consent obtained from the participants' legally authorized representatives prior to any study-specific procedures.
Treatment
The clinical trial involves the administration of **Linaclotide**, an experimental medication, which is an **agonist of guanylate cyclase C (GCC)**. Linaclotide is provided in a **hard capsule** form and is administered **orally**. The dosing regimen includes a maximum daily dose of **36 µg** and a total maximum dose of **1008 µg** over a treatment period of **4 weeks**. The active substance, linaclotide, is a protein of other origin, and the product is manufactured by AbbVie Deutschland GmbH & Co. KG. The trial aims to evaluate the safety and efficacy of linaclotide in pediatric subjects aged 6 months to less than 2 years with functional constipation.
In addition to the experimental medication, the study includes a **placebo** group, where participants receive a placebo that mimics the appearance of the linaclotide capsule but contains no active substance. The placebo is used to assess the efficacy of linaclotide by providing a comparator for evaluating the treatment's effects.
The trial also incorporates the use of **osmotic laxatives**, classified under the ATC code A06AD, which are administered **orally**. These laxatives are provided in a pharmaceutical form coded as PHF00069MIG, with a maximum daily dose of **2 grams** and a total maximum dose of **2 grams** over a treatment period of **2 days**. The osmotic laxatives serve as a non-experimental treatment to manage constipation symptoms in the study participants.
Additionally, a **stimulant laxative** is included in the trial, classified under the ATC code A06AX, and is administered via **rectal use**. This treatment is provided in a pharmaceutical form coded as PHF00103MIG, with a maximum daily dose of **1 gram** and a total maximum dose of **1 gram** over a treatment period of **1 day**. The stimulant laxative is used to support the management of constipation symptoms in the study.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The study's primary objective is to identify a tolerable, safe, and efficacious dose of linaclotide for pediatric subjects with functional constipation, with a secondary focus on evaluating the overall safety and efficacy of the treatment.
Efficacy
The efficacy of **Linaclotide** in the clinical trial will be assessed using several primary endpoints. These include the change from baseline in the 4-week overall spontaneous bowel movement (SBM) frequency rate, the change from baseline in 4-week stool consistency as measured by the Bristol Stool Form Scale, and the change from baseline in 4-week straining, all reported by the legally authorized representative (LAR), parent, guardian, or caregiver during the study intervention period. These parameters are designed to evaluate the effectiveness of Linaclotide in improving symptoms of functional constipation in pediatric subjects aged 6 months to less than 2 years.
The measurements will be collected over a 4-week period during the study intervention. The frequency of SBMs will be recorded, and stool consistency will be assessed using the Bristol Stool Form Scale, a validated tool for categorizing stool form. Straining will also be documented by the LAR, parent, guardian, or caregiver. These data points will be analyzed to determine the efficacy of Linaclotide in achieving the desired therapeutic outcomes in the target population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The Subjects' LAR/parent/guardian must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
- Individuals must be 6 months to less than 1 year and 11 months old, at the time the LAR/parent/guardian signs the informed consent in alignment with local requirements.
- Subject has weight-for-height/length ratio of ≥ 3rd percentile for age 6 months to less than 24 months at the time the LAR/parent/guardian has provided signed consent. (Investigators can choose to use CDC or WHO growth charts based on their current clinical practice).
- Subject meets Rome IV criteria for FC as outlined below: For at least 1 month before Screening (Visit 1), the subject must meet 2 or more of the following (a-e): a) 2 or fewer defecations per week (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) b) History of excessive stool retention c) History of painful or hard bowel movements (BMs) d) History of large-diameter stools e) Presence of a large fecal mass in the rectum Accompanying symptoms may include irritability, decreased appetite, and/or early satiety.
- Based on the eDiary, the Subject has an average of ≤ 2 spontaneous bowel movements (SBMs) per week during the 14 days before the enrollment/randomization day and up to the enrollment/randomization (including the morning eDiary assessments reported before administration of first dose of study intervention on the enrollment/randomization day). An SBM is defined as a bowel movement (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
- Subjects with conditions that could interfere with drug absorption including but not limited to short bowel syndrome.
- 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.
- Subjects with conditions 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
- Subjects with suspected mechanical bowel obstruction or pseudo-obstruction
- Subject did not use a protocol-specified prohibited medicine before the start of the Preintervention Period (Visit 2) or failed to meet the stable-dose requirements of certain medications
- 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 Screening (Visit 1) or is currently or planning to enroll in another clinical study or was previously enrolled in this study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 11 Sept 2023 | 5 |
 Croatia | Not Recruiting | 11 Sept 2023 | 5 |
 Germany | Not Recruiting | 11 Sept 2023 | 3 |
 Hungary | Not Recruiting | 11 Sept 2023 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Linaclotide | Test | CAPSULE, HARD | ORAL | 36 | 4 | PRD10178487 |
- | Other | PHF00069MIG | ORAL | 2 | 2 | A06AD |
Linaclotide Placebo | Placebo | N/A | — | — | — | N/A |
Linaclotide | Test | CAPSULE | ORAL | 9 | 4 | PRD10064948 |
Linaclotide | Test | CAPSULE, HARD | ORAL | 18 | 4 | PRD10121006 |
- | Other | PHF00103MIG | RECTAL USE | 1 | 1 | A06AX |