Lubiprostone for Children With Constipation

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02138136
• Collaborator: Takeda (Industry)
• Enrollment: 419
• Locations: 85
• Arm: 1
• Actual Duration (Months): 38.1
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is for children with constipation.

Children who completed 3 months of treatment in the earlier study (NCT02042183):

• were invited to participate

• will receive lubiprostone for 9 more months

• will see if lubiprostone safely relieves their constipation if taken for a whole year

Condition or Disease	Intervention/Treatment	Phase
Constipation - Functional	Drug: Lubiprostone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 419 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Long-term Safety, Efficacy, and Pharmacokinetics Study of Lubiprostone in Paediatric Subjects Aged ≥ 6 Years to < 18 Years With Functional Constipation
• Actual Study Start Date: Feb 26, 2014
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lubiprostone Participants receive lubiprostone twice daily Participants must have completed the entire 12-week treatment period during the preceding study. Those who received 12 mcg twice daily (BID) continued to receive 12 mcg, those who received 24 mcg BID continued with that dose.Those of the placebo arm in the previous study weighing less than 50 kg received 12 mcg BID and over 50 kg received 24 mcg BID during this study.

Drug: Lubiprostone; 12 or 24 mcg soft capsules for oral administration; Other Names: Amitiza®

Outcome Measures

Primary Outcome Measures

1. Median Number of Observed Weekly Spontaneous Bowel Movements (SBM) Per Month [within 9 months]

   Spontaneous bowel movements are defined as bowel movements without the aid of drugs.

Other Outcome Measures

1. Median Monthly Score on a 5-point Straining Scale Associated With Observed SBMs [within 9 months]

   Straining during observed SBMs is rated on a 5-point scale where 1=no straining and 5=extreme straining. A higher value is worse.

2. Median Monthly Score on a Stool Consistency Scale Associated With Observed SBMs [within 9 months]

   Stool consistency is rated on a 5-Point Stool Consistency Scale, where 1=normal and 5=very hard. Higher scores mean a worse outcome.

3. Median Monthly Score on a 4-point Pain Scale for Observed Abdominal Pain [within 9 months]

   Abdominal pain was rated on a scale from 1 (no pain) to 4 (very severe pain). A higher score means a worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has completed the 3-month placebo-controlled study (NCT02042183)

• Will continue to abstain from taking concomitant medication (prescribed or over-the-counter) that affects gastrointestinal motility

Exclusion Criteria:

• Has untreated faecal impaction at the time of rolling over into study

• Has significant change in medical status, newly diagnosed and uncontrolled cardiovascular, liver or lung disease, neurologic or psychiatric disorder, or other systemic disease

• Has demonstrated non-compliance with study protocol during the 3-month placebo-controlled study (NCT02042183)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Women's and Children's Hospital	Mobile	Alabama	United States	36604
2	Arizona Children's Center at Maricopa Medical Center	Phoenix	Arizona	United States	85008
3	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
4	Northwest Arkansas Pediatric Clinic	Fayetteville	Arkansas	United States	72703
5	Arkansas Childrens Hospital Research Institute	Little Rock	Arkansas	United States	72202
6	WCCT Global	Costa Mesa	California	United States	92626
7	Loma Linda University Health Care	Loma Linda	California	United States	92350
8	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
9	University of California, San Francisco	San Francisco	California	United States	94143
10	MCB Clinical Research	Colorado Springs	Colorado	United States	80910
11	Nemours/Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
12	Emmerson Clinical Research	Washington	District of Columbia	United States	20020
13	University of Florida	Gainesville	Florida	United States	32610
14	Palmetto Professional Research	Hialeah	Florida	United States	33016
15	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
16	Savin Medical Group Research Center	Miami Lakes	Florida	United States	33014
17	Acevedo Clinical Research Associates	Miami	Florida	United States	33142
18	Nemours Childrens Clinic	Pensacola	Florida	United States	32504
19	Children's Center for Digestive Health Care/GI Care for Kids	Atlanta	Georgia	United States	30342
20	Methodist Medical Center	Peoria	Illinois	United States	61602
21	PediaResearch, LLC - Newburgh	Newburgh	Indiana	United States	47630
22	UnityPoint Health Des Moines/ Blank Children's Clinic	Des Moines	Iowa	United States	50309
23	University of Iowa Children's Hospital	Iowa City	Iowa	United States	52242
24	Heartland Research Associates	Wichita	Kansas	United States	67205
25	University of Louisville Research Foundation Inc. Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
26	PediaResearch, LLC - Owensboro	Owensboro	Kentucky	United States	42301
27	Willis-Knighton Physician Network	Shreveport	Louisiana	United States	71101
28	Virgo-Carter Pediatrics	Silver Spring	Maryland	United States	20910
29	Gastrointestinal Associates, PA	Jackson	Mississippi	United States	39202
30	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
31	The Children's Mercy Hospital	Kansas City	Missouri	United States	64145
32	Pioneer Clinical Research	Bellevue	Nebraska	United States	68005
33	Smart Medical Research, Inc.	Jackson Heights	New York	United States	11372
34	NY Presbyterian Weill Cornell	New York	New York	United States	10021
35	Morgan Stanley Children's Hospital of New York Presbyterian	New York	New York	United States	10032
36	PriMed Clinical Research	Beavercreek	Ohio	United States	45431
37	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
38	Toledo Children's Hospital	Toledo	Ohio	United States	43606
39	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
40	Cyn3rgy Research	Gresham	Oregon	United States	97030
41	Square-1 Clinical Research, Inc.	Erie	Pennsylvania	United States	16506
42	St. Christopher's Hospital for Children Drexel University	Philadelphia	Pennsylvania	United States	19134
43	Children's Hospital of Pittsburgh UPMC	Pittsburgh	Pennsylvania	United States	15224
44	AAPRI Clinical Research	Warwick	Rhode Island	United States	02886
45	Coastal Pediatric Associates - James Island	Charleston	South Carolina	United States	29412
46	Coastal Clinical Research	Charleston	South Carolina	United States	29414
47	Greenville Health System	Greenville	South Carolina	United States	29615
48	Coastal Pediatrics Associates - Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
49	Spartanburg Medical Research	Spartanburg	South Carolina	United States	29303
50	The Jackson Clinic, P.C.	Jackson	Tennessee	United States	38305
51	3rd Coast Research Associates	Corpus Christi	Texas	United States	78413
52	Childrens Medical Center Dallas	Dallas	Texas	United States	75390
53	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
54	Baylor College of Medicine	Houston	Texas	United States	77030
55	Envision Clinical Research, LLC	Laredo	Texas	United States	78041
56	DCOL Center for Clinical Research	Longview	Texas	United States	75605
57	Bridgerland Clinical Research	Logan	Utah	United States	84341
58	Primary Children's Medical Center	Salt Lake City	Utah	United States	84132
59	Wee Care Pediatrics	Syracuse	Utah	United States	84075
60	University of Vermont Medical Center	Burlington	Vermont	United States	05445
61	Pediatric Research of Charlottesville, LLC	Charlottesville	Virginia	United States	22902
62	INOVA Pediatric Digestive Diseases Center	Fairfax	Virginia	United States	22031
63	Pediatric Gastroenterology Carilion Medical Center	Roanoke	Virginia	United States	24014
64	Northwest Clinicial Research Center	Bellevue	Washington	United States	98007
65	Zain Research LLC	Richland	Washington	United States	99352
66	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington	United States	98405
67	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
68	Universitair Kinderziekenhuis Brussel	Brussel		Belgium	01090
69	CHC - Clinique Saint-Joseph	Montegnee		Belgium	04420
70	Sainte Justine University Health Center	Montreal		Canada	H3T1C5
71	CHU-Bordeaux	Bordeaux		France	33000
72	Emma Children's Hospital	Amsterdam		Netherlands	1105 AZ
73	Amphia Ziekenhuis	Breda		Netherlands	4800 RK
74	Maasstad Hospital Rotterdam	Rotterdam		Netherlands	3079 DZ
75	Isala Klinieken	Zwolle		Netherlands	8025 AB
76	Medical University of Bialystok	Bialystok		Poland	15-274
77	Szpital Uniwersytecki	Bydgoszcz		Poland	85-168
78	Szpital Pediatryczny ICZMP	Lodz		Poland	93-338
79	Gabinet Lekarski Bartosc Korczowski	Rzeszow		Poland	35-210
80	Przychodnia Specjalistyczna PROSEN	Warszawa		Poland	01-231
81	Children's Memorial Health Institute	Warszaw		Poland	04-730
82	Darlington Memorial Hospital	Darlington		United Kingdom	DL3 6HZ
83	Royal London Hospital	London		United Kingdom	E1 1BB
84	Chelsea and Westminster Hospital NHS Foundation Trust	London		United Kingdom	SW10 9NH
85	Sheffield Children Hospital	Sheffield		United Kingdom	S10 2TH

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Takeda

Investigators

• Study Director: Global Clinical Leader, Mallinckrodt

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2015

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT02138136
• Other Study ID Numbers: SAG-0211PFC-11S1; 2013-004384-31
• First Posted: May 14, 2014
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Constipation; Lubiprostone

Study Results

Participant Flow

Recruitment Details	Participants who completed the 3-month placebo-controlled study (NCT02042183) were invited to enroll in this safety extension study lasting an additional 9 months.

Arm/Group Title	All Participants
Arm/Group Description	Participants received lubiprostone
Period Title: Overall Study
STARTED	419
Safety Analysis Set	419
Modified Intent to Treat (mITT)	418
COMPLETED	280
NOT COMPLETED	139

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants receive lubiprostone
Overall Participants	418
Age, Customized (Count of Participants)
6-17 years of age	418 100%
Sex: Female, Male (Count of Participants)
Female	229 54.8%
Male	189 45.2%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Netherlands	36 8.6%
Belgium	2 0.5%
United States	359 85.9%
Poland	10 2.4%
United Kingdom	10 2.4%
France	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Median Number of Observed Weekly Spontaneous Bowel Movements (SBM) Per Month
Description	Spontaneous bowel movements are defined as bowel movements without the aid of drugs.
Time Frame	within 9 months

Outcome Measure Data

Analysis Population Description

mITT with evaluable data at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants received lubiprostone
Measure Participants	418
Month 1	2.66
Month 2	2.75
Month 3	2.70
Month 4	2.75
Month 5	2.74
Month 6	2.50
Month 7	2.63
Month 8	2.63
Month 9	2.50

2. Other Pre-specified Outcome

Title	Median Monthly Score on a 5-point Straining Scale Associated With Observed SBMs
Description	Straining during observed SBMs is rated on a 5-point scale where 1=no straining and 5=extreme straining. A higher value is worse.
Time Frame	within 9 months

Outcome Measure Data

Analysis Population Description

mITT with evaluable data at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants received lubiprostone
Measure Participants	418
Month 1	1.19
Month 2	1.25
Month 3	1.14
Month 4	1.17
Month 5	1.19
Month 6	1.13
Month 7	1.00
Month 8	1.00
Month 9	1.00

3. Other Pre-specified Outcome

Title	Median Monthly Score on a Stool Consistency Scale Associated With Observed SBMs
Description	Stool consistency is rated on a 5-Point Stool Consistency Scale, where 1=normal and 5=very hard. Higher scores mean a worse outcome.
Time Frame	within 9 months

Outcome Measure Data

Analysis Population Description

mITT with evaluable data at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants receive lubiprostone
Measure Participants	418
Month 1	2.80
Month 2	2.75
Month 3	2.78
Month 4	2.78
Month 5	2.83
Month 6	2.83
Month 7	2.87
Month 8	2.90
Month 9	2.89

4. Other Pre-specified Outcome

Title	Median Monthly Score on a 4-point Pain Scale for Observed Abdominal Pain
Description	Abdominal pain was rated on a scale from 1 (no pain) to 4 (very severe pain). A higher score means a worse outcome.
Time Frame	within 9 months

Outcome Measure Data

Analysis Population Description

mITT with evaluable data at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants received lubiprostone
Measure Participants	418
Month 1	1.00
Month 2	0.99
Month 3	0.90
Month 4	0.85
Month 5	0.84
Month 6	0.82
Month 7	0.75
Month 8	0.85
Month 9	0.79

Adverse Events

Time Frame	from first open-label dose to last open-label dose plus 7 days (9 months, 7 days)
Adverse Event Reporting Description	Only treatment-emergent adverse events (AEs) are reported. Adverse events with onset dates after the administration of the first open-label dose and prior to the last open-label dose plus 7 days are considered treatment-emergent.
Arm/Group Title	All Participants
Arm/Group Description	Participants receive lubiprostone
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/419 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	13/419 (3.1%)
Gastrointestinal disorders
Faecaloma	2/419 (0.5%)	2
Irritable bowel syndrome	1/419 (0.2%)	1
Abdominal pain	1/419 (0.2%)	1
Faecal incontinence	1/419 (0.2%)	1
Constipation	3/419 (0.7%)	3
Gastritis	1/419 (0.2%)	1
Gastrointestinal obstruction	1/419 (0.2%)	1
Hepatobiliary disorders
Hepatotoxicity	1/419 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	1/419 (0.2%)	1
Nervous system disorders
Depressed level of consciousness	1/419 (0.2%)	1
Psychiatric disorders
Conversion disorder	1/419 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Tonsillar haemorrhage	1/419 (0.2%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	147/419 (35.1%)
Gastrointestinal disorders
Nausea	36/419 (8.6%)	36
Vomiting	47/419 (11.2%)	47
Abdominal pain	33/419 (7.9%)	33
Diarrhoea	27/419 (6.4%)	27
Infections and infestations
Nasopharyngitis	31/419 (7.4%)	31
Upper respiratory tract infection	19/419 (4.5%)	19
Nervous system disorders
Headache	33/419 (7.9%)	33

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.