Lubiprostone for Functional Constipation in the Under 18 Years Patients

Lubiprostone for the Treatment of Functional Constipation in the Under 18 Years Patients: A Randomized, Controlled Trial.

The investigators will enroll subjects 8 - < 18 years of age, fulfilling Rome IV criteria for functional constipation.

Participants will be randomly assigned to either Lubiprostone treatment (study group), or the control group (will receive either lactulose or Bisacodyl tablets).

safety and efficacy will be assessed.

Study Overview

• Status: Completed
• Conditions: Drug Side Effect; Treatment Efficacy; Clinical Efficacy
• Intervention / Treatment: Drug: Lubiprostone Pill; Drug: Lactulose Oral Liquid Product; Drug: Bisacodyl 5 MG; Drug: Sodium Picosulfate

Detailed Description

The investigators will enroll 274 subjects who will be randomly divided equally into interventional and control groups.

Participants and their parents/legal guardians will be instructed to administer the doses at least 5 hours apart with meals and a large volume of fluid.

The control group will receive lactulose 1 mL/kg, once or twice daily (maximum 60 mL/day or Bisacodyl tablet (5 mg/tablet) in a dose of 2 tab/day for < 12 years or 3 tab/day for > 12 years.

Both arms will receive the treatment for 12 weeks followed by 4 weeks follow-up after the end of treatment (week 16).

Participants (and their guardians) will be instructed to regularly document the number of spontaneous bowel motions/week and to define their Bristol chart category for every bowel motion. In addition, the participants will be encouraged to contact the trial team if any adverse events appeared. This is in addition to regular visits at 0, 2, 8, 12 weeks for assessment of safety (efficacy will be assessed at weeks 8, 12, and 16).

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21521
    • Alexandria main university hospital
  • Alexandria, Egypt, 21521
    • Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients 8 - < 18 years of age who have a confirmed diagnosis of Pediatric functional constipation according to the Rome IV criteria, who give written informed consent personally or from their legal guardians.
• Discontinuation of any medication affecting gastrointestinal (GI) motility at least 2 weeks before starting the treatment allocation.
• Patient's daily diary that indicates an average of < 3 weekly spontaneous bowel movements (SBMs), with ≥ 25% of SBMs involving at least some straining and/or a 5-point modified Bristol Stool Form Scale type 1 or 2.
• Patients who completed the study protocol.

Exclusion Criteria:

1. If the patient's constipation is attributed to any of the following: physical, mental, or cognitive illness, inflammatory bowel disease, medication, anatomical, neurological, endocrine, or metabolic factors.
2. If the patient is a candidate for or underwent abdominal surgery, or has any condition other than constipation that could affect gastrointestinal motility or defecation.
3. Patients suffering from Hirschsprung's disease.
4. Patients experiencing any alarming signs e.g. unexplained significant weight loss.
5. Untreated fecal impaction at the time of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Investigational Arm; Patients will receive lubiprostone capsules (Amiprostone 8 and 24 mcg, or Lubicont 8 mcg); Patients weighing <50 kg will be given lubiprostone at doses of 8 mcg/8 hours.; Patients weighing ≥ 50 kg will be given lubiprostone at doses of 24 mcg BID.; Patients and their parents/legal guardians will be instructed to administer the doses at least 5 hours apart with meals and a large volume of fluid.	Drug: Lubiprostone Pill; Oral pills for constipation (Lubiprostone) will be given in a dose range from 24 mcg once daily to 24 mcg twice daily according to the participant weight.; Other Names: Amiprostone 8 mcg caps; Amiprostone 24 mcg caps; Lubicont 8 mcg caps
ACTIVE_COMPARATOR: Control Arm; Subjects will receive the conventional therapy (one or a combination of the following): Lactulose " Lactulose, or Duphalac syrup" at a dose of 1 ml/kg once or twice daily (maximum 60 mL/day),; Bisacodyl tablets " Bisacodyl 5 mg/tablet" in a dose of 2 tab/day for < 12 years or 3 tab/day for > 12 years, or; Sodium Picosulfate 0.75% drops (Picolax drops) in a daily dose of 2.5-20 mg/day.	Drug: Lactulose Oral Liquid Product; Lactulose " Lactulose, or Duphalac syrup" at a dose of 1 ml/kg once or twice daily (maximum 60 mL/day); Other Names: Lactulose OR Duphalac; Drug: Bisacodyl 5 MG; Bisacodyl tablet (5 mg/tablet) in a dose of 2 tab/day for < 12 years or 3 tab/day for > 12 years; Other Names: Bisacodyl 5 mg tablets; Drug: Sodium Picosulfate; Sodium Picosulfate 0.75% drops in a daily dose of 2.5-20 mg/day; Other Names: Bisadyl 0.75% drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome	Spontaneous bowel motions (SBM) ≥ 1 SBM/week increase in the frequency compared with baseline, and ≥ 3 SBMs/week for at least 8 weeks, including the last 4 study weeks and the 4 weeks of follow-up.	At study week 16.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early spontaneous bowel motions	Number of participants who experienced first SBM within 48 hours after dose initiation.	First 48 hours after first drug dose.
First dose response time	The time between first dose of treatment and the first SBM.	1st week of treatment
Number of Spontaneous Bowel Motions/Week.	Number of Spontaneous Bowel Motions/Week.	At study week Week 8, 12.
Responders rate	Responders rate at week 8, 12, 16.	At study week Week 8, 12, 16.

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Sameh A. Lashen, MD (Ph.D.), Faculty of Medicine, Alexandria University - Alexandria

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2022
• Primary Completion (ACTUAL): August 25, 2022
• Study Completion (ACTUAL): November 1, 2022

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (ACTUAL): December 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 12, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Adolescent; Children; Lubiprostone; Drug safety; Functional constipation; Spontaneous Bowel Motions
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Signs and Symptoms, Digestive; Constipation; Drug-Related Side Effects and Adverse Reactions; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Membrane Transport Modulators; Cathartics; Chloride Channel Agonists; Laxatives; Lactulose; Bisacodyl; Picosulfate sodium; Lubiprostone
• Other Study ID Numbers: 0305299

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: patient personal and identification data will not be available for sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No