Pharmacodynamic, Pharmacokinetic, and Tolerability Study of a Liquid Form of Lubiprostone in Adult Subjects With Chronic Idiopathic Constipation

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01993875
• Collaborator: Sucampo Pharma Americas, LLC (Industry), Takeda (Industry), Sucampo AG (Industry)
• Enrollment: 164
• Locations: 11
• Arms: 2
• Duration (Months): 3
• Patients Per Site: 14.9
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

To evaluate the pharmacodynamics and tolerability of a liquid formulation of lubiprostone, as compared to matching placebo, when administered orally to subjects with chronic idiopathic constipation. Additionally, liquid formulation pharmacokinetics, including a comparison of fed and fasted pharmacokinetics, of the liquid formulation will be performed in a subset of subjects.

Condition or Disease	Intervention/Treatment	Phase
Chronic Idiopathic Constipation	Drug: Lubiprostone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Double-blinded, Multicenter Study of the Pharmacodynamics, Pharmacokinetics, and Tolerability of a Liquid Form of Lubiprostone in Adult Subjects With Chronic Idiopathic Constipation
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lubiprostone	Drug: Lubiprostone; Liquid formulation, 12 mcg x 2 pumps administered orally twice daily (BID)
Placebo Comparator: Placebo	Drug: Placebo; Matching liquid placebo, 0 mcg x 2 pumps administered orally twice daily (BID)

Outcome Measures

Primary Outcome Measures

1. Number of Spontaneous Bowel Movements (SBMs) Within 1 Week [within 1 week]

   SBM is defined as any bowel movement (BM) that did not occur within the 24-hour period following use of a rescue medication.

Secondary Outcome Measures

1. Consistency of SBMs at Week 1 [at Week 1]

   Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid.

2. Overall Stool Consistency at Week 1 [at Week 1]

   Overall stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid.

3. Mean Change From Baseline in Stool Consistency at Week 1 [Baseline and Week 1]

   Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. The change from baseline was calculated as post-treatment value (mean) minus the baseline value (mean).

4. Overall Straining at Week 1 [Week 1]

   Bowel straining was rated on a scale of 0 to 4 (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe).

5. Mean Change From Baseline in Straining at Week 1 [Week 1]

   Bowel straining was rated as 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. The change from baseline was calculated as post-treatment value minus the baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Medically-confirmed diagnosis of chronic idiopathic constipation

• Willing to discontinue use of prescribed or over-the-counter (OTC) medication that affects gastrointestinal motility during the study

• Stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors

Exclusion Criteria:

• Any gastrointestinal (GI) condition, other than constipation, affecting GI motility or defecation.

• 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		Anniston	Alabama	United States	36207
2		Anaheim	California	United States	92801
3		DeLand	Florida	United States	32720
4		Hollywood	Florida	United States	33024
5		Orlando	Florida	United States	32809
6		South Miami	Florida	United States	33143
7		Overland Park	Kansas	United States	66212
8		Marlton	New Jersey	United States	08053
9		Raleigh	North Carolina	United States	27612
10		Salt Lake City	Utah	United States	84106
11		West Bend	Wisconsin	United States	53095

Sponsors and Collaborators

• Mallinckrodt
• Sucampo Pharma Americas, LLC
• Takeda
• Sucampo AG

Investigators

• Study Director: Global Clinical Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT01993875
• Other Study ID Numbers: SCMP-0211-301
• First Posted: Nov 25, 2013
• Last Update Posted: Dec 13, 2019
• Last Verified: Jul 1, 2015

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Constipation; Lubiprostone

Study Results

Participant Flow

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 microgram (mcg) x 2 pumps administered orally twice daily (BID).	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Period Title: Overall Study
STARTED	82	82
COMPLETED	75	76
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	Lubiprostone	Placebo	Total
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.	Total of all reporting groups
Overall Participants	82	82	164
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	78 95.1%	75 91.5%	153 93.3%
>=65 years	4 4.9%	7 8.5%	11 6.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.2 (12.51)	45.0 (12.82)	46.1 (12.68)
Sex: Female, Male (Count of Participants)
Female	55 67.1%	58 70.7%	113 68.9%
Male	27 32.9%	24 29.3%	51 31.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 35.4%	29 35.4%	58 35.4%
Not Hispanic or Latino	53 64.6%	53 64.6%	106 64.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%	1 1.2%	2 1.2%
Asian	0 0%	2 2.4%	2 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	42 51.2%	38 46.3%	80 48.8%
White	38 46.3%	40 48.8%	78 47.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.2%	1 1.2%	2 1.2%
Region of Enrollment (participants) [Number]
United States	82 100%	82 100%	164 100%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.5 (5.03)	30.9 (6.50)	30.2 (5.84)
Previous AMITIZA use at randomization (Count of Participants)
No	80 97.6%	81 98.8%	161 98.2%
Yes	2 2.4%	1 1.2%	3 1.8%

Outcome Measures

1. Primary Outcome

Title	Number of Spontaneous Bowel Movements (SBMs) Within 1 Week
Description	SBM is defined as any bowel movement (BM) that did not occur within the 24-hour period following use of a rescue medication.
Time Frame	within 1 week

Outcome Measure Data

Analysis Population Description

Modified Intention to Treat (mITT), defined as all participants who received at least 1 dose of study medication.

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [number of SBMs]	4.6 (3.33)	4.0 (3.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1290
	Comments	Treatment p-value is from an analysis of co-variance (ANCOVA) using the SBM rate as the dependent variable, treatment as fixed effect, and baseline rate as random effect.
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Consistency of SBMs at Week 1
Description	Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid.
Time Frame	at Week 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [score on a scale]	3.2 (3.12)	2.4 (3.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1290
	Comments	Treatment p-value is from an ANCOVA using the SBM rate as the dependent variable, treatment as fixed effect, and baseline rate as random effect.
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Overall Stool Consistency at Week 1
Description	Overall stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid.
Time Frame	at Week 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [score on a scale]	3.3 (1.38)	3.0 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2177
	Comments	Treatment p-value is from an ANCOVA using the mean stool consistency score as the dependent variable, treatment as fixed effect, and the baseline consistency score as random effect.
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Stool Consistency at Week 1
Description	Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. The change from baseline was calculated as post-treatment value (mean) minus the baseline value (mean).
Time Frame	Baseline and Week 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [Units on a scale]	1.8 (0.91)	1.9 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2177
	Comments	Treatment p-value is from an ANCOVA using the mean stool consistency score as the dependent variable, treatment as fixed effect, and the baseline consistency score as random effect.
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Overall Straining at Week 1
Description	Bowel straining was rated on a scale of 0 to 4 (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe).
Time Frame	Week 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [Units on a scale]	1.8 (0.91)	1.9 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0664
	Comments	Treatment p-value is from an ANCOVA using the mean straining score as the dependent variable, treatment as fixed effect, and the baseline straining score as random effect.
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Mean Change From Baseline in Straining at Week 1
Description	Bowel straining was rated as 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. The change from baseline was calculated as post-treatment value minus the baseline value.
Time Frame	Week 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 microgram (mcg) x 2 pumps administered orally twice daily (BID).	Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
Measure Participants	82	82
Mean (Standard Deviation) [Units on a scale]	-1.1 (0.94)	-0.8 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lubiprostone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0664
	Comments	Treatment p-value is from an ANCOVA using the mean straining score as the dependent variable, treatment as fixed effect, and the baseline mean score as random effect.
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Up to 7 Weeks
Arm/Group Title	Lubiprostone		Placebo
Arm/Group Description	Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID.		Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID.
All Cause Mortality
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/82 (0%)
Serious Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/82 (0%)
Other (Not Including Serious) Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/82 (25.6%)		15/82 (18.3%)
Gastrointestinal disorders
Nausea	9/82 (11%)		1/82 (1.2%)
Flatulence	7/82 (8.5%)		6/82 (7.3%)
Abdominal distension	1/82 (1.2%)		3/82 (3.7%)
Abdominal pain	1/82 (1.2%)		3/82 (3.7%)
Infections and infestations
Upper respiratory tract infection	2/82 (2.4%)		0/82 (0%)
Nervous system disorders
Headache	6/82 (7.3%)		9/82 (11%)
Presyncope	5/82 (6.1%)		0/82 (0%)
Dizziness	2/82 (2.4%)		0/82 (0%)
Respiratory, thoracic and mediastinal disorders
Throat irritation	2/82 (2.4%)		0/82 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.