Lubiprostone for Functional Constipation in the Under 18 Years Patients

Sponsor

Alexandria University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05144295

Collaborator

(none)

274

Enrollment

Locations

Arms

Anticipated Duration (Months)

137

Patients Per Site

12.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Clinical Efficacy Treatment Efficacy Drug Side Effect	Drug: Lubiprostone Pill Drug: Lactulose Oral Liquid Product Drug: Bisacodyl 5 MG Drug: Sodium Picosulfate	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

274 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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).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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Primary outcome [At study week 16.]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.