Lubiprostone for Functional Constipation in the Under 18 Years Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Clinical Efficacy, Treatment Efficacy, Drug Side Effect

Intervention / Treatment
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* Drug: Lubiprostone Pill
* Drug: Lactulose Oral Liquid Product
* Drug: Bisacodyl 5 MG
* Drug: Sodium Picosulfate


Participation Criteria
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Eligibility Criteria
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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: 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. 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. Patients suffering from Hirschsprung's disease. Patients experiencing any alarming signs e.g. unexplained significant weight loss. Untreated fecal impaction at the time of enrollment.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients assigned to lubiprostone will receive a dose based on their weight at the time of enrollment. patients weighing <50 kg and ≥ 50 kg will be given lubiprostone at doses of 8 mg TID and 24 mg BID, respectively. Patients and their parents/legal guardians will be instructed to administer the doses at least 5 hours apart with meals and large volume of fluid. The control group will receive the conventional therapy (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).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Arm<br>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<br>* 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.<br>* Other names: Lubicont 8 mcg caps;|
| Active Comparator: Control Arm<br>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<br>* Lactulose  Lactulose, or Duphalac syrup at a dose of 1 ml/kg once or twice daily (maximum 60 mL/day)<br>* Other names: Lactulose OR Duphalac;Drug: Bisacodyl 5 MG<br>* Bisacodyl tablet (5 mg/tablet) in a dose of 2 tab/day for < 12 years or 3 tab/day for > 12 years<br>* Other names: Bisacodyl 5 mg tablets;Drug: Sodium Picosulfate<br>* Sodium Picosulfate 0.75% drops in a daily dose of 2.5-20 mg/day<br>* Other names: Bisadyl 0.75% drops;|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lubiprostone, Functional constipation, Adolescent, Children, Spontaneous Bowel Motions, Drug safety