Lubiprostone in Children With Functional Constipation

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02042183
• Collaborator: Sucampo AG (Industry)
• Enrollment: 606
• Locations: 117
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Study to determine if children (6-17 years old) with functional constipation will respond to being treated with lubiprostone for 12 weeks.

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

Detailed Description

Dose administration details:

• Participants with a body weight <50 kg at baseline received Lubiprostone 12 mcg BID for 12 weeks. If the dose was safe but did not show any efficacy at Week 1, dosage was increased to 24 mcg BID.

• Participants with a body weight >50 kg at baseline received Lubiprostone 24 mcg BID for 12 weeks. If the dose was unsafe at Week 1, dosage was decreased to 12 mcg BID.

Study Design

• Study Type: Interventional
• Actual Enrollment: 606 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Placebo controlledPlacebo controlled
• Masking: Double (Participant, Investigator)
• Masking Description: While the care provider and outcomes assessor were also blinded, this was classified as a double-blind trial
• Primary Purpose: Treatment
• Official Title: A Multicentre, Randomised, Placebo-controlled, Double-blinded Study of the Efficacy, Safety, and Pharmacokinetics of Lubiprostone in Paediatric Subjects Aged ≥ 6 Years to < 18 Years With Functional Constipation
• Actual Study Start Date: Dec 13, 2013
• Actual Primary Completion Date: Jul 27, 2016
• Actual Study Completion Date: Jul 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lubiprostone Participants receive lubiprostone twice daily (BID) up to 12 weeks	Drug: Lubiprostone; 12 or 24 mcg soft capsules of lubiprostone for oral administration, depending on baseline weight and response during week 1; Other Names: Amitiza
Placebo Comparator: Placebo Participants receive placebo BID up to 12 weeks	Drug: Placebo; 0 mcg soft capsules of placebo for oral administration; Other Names: Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants Classified as Overall Responders at Week 12 [at Week 12]

   An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline.

Secondary Outcome Measures

1. Mean Number of SBMs Observed Each Week for 12 Weeks [within 12 Weeks]

   Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Medically-confirmed diagnosis of Functional Constipation per Rome III Diagnostic Criteria for Childhood Functional Constipation

• At least 6 years of age but less than 18 years of age at the time of randomisation

• Only stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors are allowed if subject is taking antidepressants

Exclusion Criteria:

• Any gastrointestinal (GI) condition, other than constipation and/or irritable bowel syndrome (IBS), affecting GI motility or defecation

• Untreated faecal impaction at the time of screening

• Medical/surgical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Pediatric Gastroenterology	Birmingham	Alabama	United States	35233
2	University of South Alabama Women's and Children's Hospital	Mobile	Alabama	United States	36604
3	Arizona Children's Center at Maricopa Medical Center	Phoenix	Arizona	United States	85008
4	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
5	Northwest Arkansas Pediatric Clinic	Fayetteville	Arkansas	United States	72703
6	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas	United States	72202
7	Applied Clinical Research of Arkansas	Little Rock	Arkansas	United States	72212
8	WCCT Global	Costa Mesa	California	United States	92626
9	Loma Linda University Health Care	Loma Linda	California	United States	92350
10	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
11	Children's Hospital of Orange County	Orange	California	United States	92868
12	University of California, San Francisco	San Francisco	California	United States	94143
13	MCB Clinical Research	Colorado Springs	Colorado	United States	80910
14	Nemours/Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
15	Emmerson Clinical Research	Washington	District of Columbia	United States	20020
16	University of Florida	Gainesville	Florida	United States	32610
17	Palmetto Professional Research	Hialeah	Florida	United States	33016
18	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
19	Savin Medical Group Research Center	Miami Lakes	Florida	United States	33014
20	Acevedo Clinical Research Associates	Miami	Florida	United States	33142
21	Digestive & Liver Center of Florida	Orlando	Florida	United States	32819
22	Nemours Childrens Clinic	Pensacola	Florida	United States	32504
23	Children's Center for Digestive Healthcare/GI Care for Kids	Atlanta	Georgia	United States	30342
24	Center For Children's Digestive Health	Park Ridge	Illinois	United States	60068
25	Methodist Medical Center	Peoria	Illinois	United States	61602
26	PediaResearch, LLC - Newburgh	Newburgh	Indiana	United States	47630
27	UnityPoint Health Des Moines/ Blank Children's Clinic	Des Moines	Iowa	United States	50309
28	University of Iowa Children's Hospital	Iowa City	Iowa	United States	52242
29	Heartland Research Associates	Wichita	Kansas	United States	67205
30	University of Louisville Research Foundation Inc. Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
31	PediaResearch, LLC - Owensboro	Owensboro	Kentucky	United States	42301
32	Children's Hospital	New Orleans	Louisiana	United States	70118
33	Willis-Knighton Physician Network	Shreveport	Louisiana	United States	71101
34	Johns Hopkins Children's Center	Baltimore	Maryland	United States	21287
35	Virgo-Carter Pediatrics	Silver Spring	Maryland	United States	20910
36	Boston Children's Hospital	Boston	Massachusetts	United States	02115
37	Mayo Clinic	Rochester	Minnesota	United States	55905
38	Gastrointestinal Associates, PA	Jackson	Mississippi	United States	39202
39	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
40	The Children's Mercy Hospital	Kansas City	Missouri	United States	64145
41	Pioneer Clinical Research	Bellevue	Nebraska	United States	68005
42	Midwest Children's Health Research Institute	Lincoln	Nebraska	United States	68504
43	Digestive Diseases and Nutrition Center Women and Childrens Hospital of Buffalo	Buffalo	New York	United States	14222
44	Smart Medical Research, Inc.	Jackson Heights	New York	United States	11372
45	NY Presbyterian Weill Cornell	New York	New York	United States	10021
46	Morgan Stanley Children's Hospital of New York Presbyterian	New York	New York	United States	10032
47	UNC School of Medicine	Chapel Hill	North Carolina	United States	27599
48	PriMed Clinical Research	Beavercreek	Ohio	United States	45431
49	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
50	Toledo Children's Hospital	Toledo	Ohio	United States	43606
51	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
52	Cyn3rgy Research	Gresham	Oregon	United States	97030
53	Square-1 Clinical Research, Inc.	Erie	Pennsylvania	United States	16506
54	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
55	St. Christopher's Hospital for Children/Drexel University	Philadelphia	Pennsylvania	United States	19134
56	Children's Hospital of Pittsburgh UPMC	Pittsburgh	Pennsylvania	United States	15224
57	AAPRI Clinical Research	Warwick	Rhode Island	United States	02886
58	Coastal Pediatric Associates - James Island	Charleston	South Carolina	United States	29412
59	Coastal Clinical Research	Charleston	South Carolina	United States	29414
60	Greenville Health System	Greenville	South Carolina	United States	29615
61	Coastal Pediatrics Associates - Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
62	Spartanburg Medical Research	Spartanburg	South Carolina	United States	29303
63	The Jackson Clinic, P.C.	Jackson	Tennessee	United States	38305
64	Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38105
65	Monroe Carell Junior Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37232
66	Texas Tech University Health Sciences Center	Amarillo	Texas	United States	79106
67	Austin Center for Clinical Research	Austin	Texas	United States	78756
68	A1 Clinical Research	Baytown	Texas	United States	77521
69	3rd Coast Research Associates	Corpus Christi	Texas	United States	78413
70	Childrens Medical Center Dallas	Dallas	Texas	United States	75390
71	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
72	Baylor College of Medicine	Houston	Texas	United States	77030
73	Envision Clinical Research, LLC	Laredo	Texas	United States	78041
74	DCOL Center for Clinical Research	Longview	Texas	United States	75605
75	Medical Clinics of Sealy	Sealy	Texas	United States	77474
76	Bridgerland Clinical Research	Logan	Utah	United States	84341
77	Primary Children's Medical Center	Salt Lake City	Utah	United States	84132
78	Wee Care Pediatrics	Syracuse	Utah	United States	84075
79	University of Vermont Medical Center	Burlington	Vermont	United States	05445
80	Pediatric Research of Charlottesville, LLC	Charlottesville	Virginia	United States	22902
81	INOVA Pediatric Digestive Diseases Center	Fairfax	Virginia	United States	22031
82	The Children's Hospital of the King's Daughter	Norfolk	Virginia	United States	23507
83	Pediatric Gastroenterology Carilion Medical Center	Roanoke	Virginia	United States	24014
84	Northwest Clinicial Research Center	Bellevue	Washington	United States	98007
85	Zain Research LLC	Richland	Washington	United States	99352
86	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington	United States	98405
87	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	58226
88	Universitair Kinderziekenhuis Brussel	Brussel		Belgium	01090
89	University Hospital Gasthuisberg	Leuven		Belgium	03000
90	CHC - Clinique Saint-Joseph	Montegnee		Belgium	04420
91	London Health Sciences Centre	London	Ontario	Canada	N6C 2V5
92	Centre de recherche du CHUS	Sherbrooke	Quebec	Canada	J1H 5N4
93	Sainte Justine University Health Center	Montreal		Canada	H3T 1C5
94	CHU-Bordeaux	Bordeaux		France	33000
95	Groupe Hospitalier Est	Bron		France	69677
96	Hôpital Necker	Paris-Cedex		France	75743
97	Armand-Trousseau Teaching Hospital	Paris		France	75012
98	Emma Children's Hospital	Amsterdam		Netherlands	1105 AZ
99	Amphia Ziekenhuis	Breda		Netherlands	4800 RK
100	Maasstad Hospital Rotterdam	Rotterdam		Netherlands	3079 DZ
101	Isala Klinieken	Zwolle		Netherlands	8025 AB
102	Medical University of Bialystok	Bialystok		Poland	15-274
103	Szpital Uniwersytecki	Bydgoszcz		Poland	85-168
104	ATOPIA Poradnie Specjalistyczne	Krakow		Poland	31-159
105	Medical University of Lodz	Lodz		Poland	91-738
106	Szpital Pediatryczny ICZMP	Lodz		Poland	93-338
107	Gabinet Lekarski Bartosc Korczowski	Rzeszow		Poland	35-210
108	Przychodnia Specjalistyczna PROSEN	Warszawa		Poland	01-231
109	Children's Memorial Health Institute	Warszaw		Poland	00-632
110	Children's Memorial Health Institute	Warszaw		Poland	04-730
111	Kent and Canterbury Hospital	Canterbury		United Kingdom	CT1 3NG
112	Darlington Memorial Hospital	Darlington		United Kingdom	DL3 6HZ
113	Royal Hospital for Sick Children	Glasgow		United Kingdom	G3 8SJ
114	Royal London Hospital	London		United Kingdom	E1 1BB
115	Chelsea and Westminster Hospital NHS Foundation Trust	London		United Kingdom	SW10 9NH
116	Great Ormond Street Hospital for children NHS Foundation Trust	London		United Kingdom	WC1N 3JH
117	Sheffield Children Hospital	Sheffield		United Kingdom	S10 2TH

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Sucampo AG

Investigators

• Study Director: Clinical Team Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT02042183
• Other Study ID Numbers: SAG/0211PFC-1131; 2013-004384-31; EMEA-000245-PIP01-08
• First Posted: Jan 22, 2014
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 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

Pre-assignment Detail	The two weeks between screening and treatment were used as a washout period for disallowed medications.

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants receive lubiprostone twice daily (BID)	Participants receive placebo BID up to 12 weeks
Period Title: Overall Study
STARTED	404	202
Safety Population	400	195
Modified Intent-to-treat (mITT)	399	195
COMPLETED	339	166
NOT COMPLETED	65	36

Baseline Characteristics

Arm/Group Title	Lubiprostone	Placebo	Total
Arm/Group Description	Participants receive lubiprostone BID up to 12 weeks	Participants receive placebo BID up to 12 weeks	Total of all reporting groups
Overall Participants	404	202	606
Age, Customized (Count of Participants)
6-9 years	142 35.1%	66 32.7%	208 34.3%
10-13 years	153 37.9%	78 38.6%	231 38.1%
14-17 years	104 25.7%	51 25.2%	155 25.6%
Sex: Female, Male (Count of Participants)
Female	216 53.5%	106 52.5%	322 53.1%
Male	183 45.3%	89 44.1%	272 44.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	76 18.8%	44 21.8%	120 19.8%
Not Hispanic or Latino	323 80%	151 74.8%	474 78.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	3 1.5%	3 0.5%
Asian	3 0.7%	3 1.5%	6 1%
Native Hawaiian or Other Pacific Islander	1 0.2%	1 0.5%	2 0.3%
Black or African American	67 16.6%	39 19.3%	106 17.5%
White	308 76.2%	138 68.3%	446 73.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	20 5%	11 5.4%	31 5.1%
Region of Enrollment (participants) [Number]
Canada	5 1.2%	7 3.5%	12 2%
Netherlands	14 3.5%	32 15.8%	46 7.6%
Belgium	1 0.2%	3 1.5%	4 0.7%
United States	174 43.1%	348 172.3%	522 86.1%
Poland	3 0.7%	8 4%	11 1.8%
United Kingdom	4 1%	6 3%	10 1.7%
France	1 0.2%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Classified as Overall Responders at Week 12
Description	An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline.
Time Frame	at Week 12

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants receive lubiprostone BID for up to 12 weeks	Participants receive placebo BID for up to 12 weeks.
Measure Participants	399	195
Count of Participants [Participants]	76 18.8%	28 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1609
	Comments	Cochran-Mantel-Haenszel (CMH) test stratified by baseline spontaneous bowel movement (SBM) frequency (<1.5 or ≥1.5)
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Mean Number of SBMs Observed Each Week for 12 Weeks
Description	Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1.
Time Frame	within 12 Weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants receive lubiprostone BID up to 12 weeks	Participants receive placebo BID up to 12 weeks
Measure Participants	399	195
at Baseline	1.40 (0.836)	1.42 (0.855)
at Week 1	2.65 (2.137)	2.50 (2.117)
at Week 2	2.68 (2.422)	2.69 (2.328)
at Week 3	2.85 (2.446)	2.59 (2.435)
at Week 4	2.94 (2.531)	2.69 (2.499)
at Week 5	2.91 (2.498)	2.68 (2.495)
at Week 6	2.91 (2.454)	2.65 (2.163)
at Week 7	2.81 (2.483)	2.75 (2.704)
at Week 8	2.94 (2.501)	2.64 (2.444)
at Week 9	2.83 (2.286)	2.37 (1.875)
at Week 10	2.68 (2.326)	2.40 (2.103)
at Week 11	2.78 (2.251)	2.60 (2.362)
at Week 12	2.90 (2.497)	2.75 (2.530)

Adverse Events

Time Frame	Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks
Adverse Event Reporting Description	Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Arm/Group Title	Lubiprostone		Placebo
Arm/Group Description	Participants receive lubiprostone BID for up to 12 weeks		Participants received placebo BID for up to 12 weeks
All Cause Mortality
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/400 (0%)		0/195 (0%)
Serious Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/400 (2.8%)		7/195 (3.6%)
Gastrointestinal disorders
Faecaloma	4/400 (1%)		2/195 (1%)
Constipation	0/400 (0%)		2/195 (1%)
General disorders
Chest pain	1/400 (0.3%)		0/195 (0%)
Immune system disorders
Anaphylactoid reaction	1/400 (0.3%)		0/195 (0%)
Infections and infestations
Cellulitis	1/400 (0.3%)		0/195 (0%)
Injury, poisoning and procedural complications
Ligament sprain	0/400 (0%)		1/195 (0.5%)
Nervous system disorders
Epilepsy	0/400 (0%)		1/195 (0.5%)
Psychiatric disorders
Suicidal ideation	1/400 (0.3%)		1/195 (0.5%)
Major depression	1/400 (0.3%)		0/195 (0%)
Hand-foot-and-mouth disease	1/400 (0.3%)		0/195 (0%)
Skin and subcutaneous tissue disorders
Rash	1/400 (0.3%)		0/195 (0%)
Surgical and medical procedures
Meniscus operation	0/400 (0%)		1/195 (0.5%)
Other (Not Including Serious) Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	234/400 (58.5%)		82/195 (42.1%)
Gastrointestinal disorders
Nausea	57/400 (14.3%)		14/195 (7.2%)
Vomiting	45/400 (11.3%)		12/195 (6.2%)
Abdominal pain	42/400 (10.5%)		23/195 (11.8%)
Diarrhoea	28/400 (7%)		6/195 (3.1%)
Abdominal pain upper	20/400 (5%)		6/195 (3.1%)
Infections and infestations
Pharyngitis streptococcal	8/400 (2%)		11/195 (5.6%)
Nervous system disorders
Headache	34/400 (8.5%)		10/195 (5.1%)

Limitations/Caveats

Outcome measures were not identified as such in the protocol, and some tables were recalculated at the request of the Food and Drug Administration, so revised data necessary to calculate the primary endpoint were posted.

More Information

Certain Agreements

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