Clinical Trials Register

Summary
EudraCT Number:	2010-022991-29
Sponsor's Protocol Code Number:	SMR/0211OBD-1033
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-12-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2010-022991-29

A.3

Full title of the trial

A Multicenter, Randomized, Placebo-controlled, Double-blinded Study of the Efficacy and Safety of Lubiprostone in Patients with Opioid-induced Bowel Dysfunction

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Effectiveness and Safety of Lubiprostone for Treatment of Opioid-induced Bowel Dysfunction

A.4.1

Sponsor's protocol code number

SMR/0211OBD-1033

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01298219

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sucampo Pharma Americas, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sucampo Pharma Americas, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sucampo Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	4520 East-West Hwy, Suite 300
B.5.3.2	Town/ city	Bethesda
B.5.3.3	Post code	20814
B.5.3.4	Country	United States
B.5.4	Telephone number	00-1301-961-3400
B.5.5	Fax number	00-1240-223-3655
B.5.6	E-mail	OpalStudy@sucampo.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Amitiza
D.2.1.1.2	Name of the Marketing Authorisation holder	Sucampo Pharma Americas, Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lubiprostone
D.3.2	Product code	RU-0211
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lubiprostone
D.3.9.1	CAS number	136790-76-6
D.3.9.2	Current sponsor code	RU-0211
D.3.9.3	Other descriptive name	SPI-0211
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	24
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Synthetic prostone

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, soft
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Opioid-induced Bowel Dysfunction

E.1.1.1

Medical condition in easily understood language

Opioid-induced Bowel Dysfunction

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10061247
E.1.2	Term	Intestinal functional disorder
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy and safety of oral lubiprostone at 48 mcg/day (24 mcg BID), as compared to placebo, when administered orally for 12 weeks to subjects with OBD.

E.2.2

Secondary objectives of the trial

N/A

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is ≥18 years of age.
2. Subject has been treated consistently for chronic, non-cancer-related pain with any oral, transdermal, intravenous or subcutaneous opioid (full agonist) other than methadone for at least 30 days prior to screening, and will continue opioid therapy throughout the study.
3. Subject must have OBD, which is defined as having an average of <3 spontaneous bowel movements (SBMs) per week during the screening period (with “spontaneous” defined as bowel movements [BMs] occurring without the use of laxatives/stool softeners) and at least one of the following for at least 25% of SBMs during each week of the screening period (as reported in the daily diary) :
• Hard or very hard stools;
• Sensation of incomplete evacuation; and/or
• Moderate to very severe straining associated with SBMs.
4. If subject has a history of chronic constipation (≥ 90 days), condition of constipation must have been exacerbated by the initiation of opioid treatment.
5. If subject is taking concomitant medication (prescribed or over-the-counter) that affects gastrointestinal motility (other than opioid therapy), he/she must discontinue use from the Screening Visit through the completion of the study; these medications include:
• Anticholinergics*, anti-spasmodics, cholinesterase inhibitors, anti-diarrhea, anti-constipation, or prokinetic agents;
• Laxative agents, including homeopathic remedies;
• Tricyclic antidepressants; and
• Any medications at the discretion of the Investigator known to relieve or cause constipation, bloating, or other constipation-related symptoms.
6. If subject has confirmed diagnosis of clinical depression and he/she has been treated with SSRIs, SNRIs, or MAO inhibitors, treatment must have been at a stable dose for at least 30 days prior to the Screening Visit and not likely to change during the study.
7. Subject is willing to discontinue use of laxative and stool softeners from the Screening Visit through the completion of the study (use of approved rescue laxatives will be allowed under certain protocol-specified circumstances).
8. If subject is taking a fiber supplement, usage must have been at a stable dose and schedule for at least 30 days prior to the Screening Visit and not likely to change during the study.
9. Subject must be willing and able to fill out his/her own electronic diary and can comply with daily data collection.
10. Subject daily diary is at least 70% compliant for the screening period.
11. Subject is capable of making an informed decision, and has read, understood, and signed the approved Informed Consent Form.

*Except ipratropium bromide or any inhaled or nasal-spray forms of this medication.

E.4

Principal exclusion criteria

1. Subject is receiving opioid therapy for cancer-related pain, abdominal pain, scleroderma, and/or for the management of drug addiction.
2. Subject is receiving methadone, methadone HCl, or a congener of methadone either alone or as part of opioid regimen.
3. Subject has current evidence of, or has been treated for, cancer within the past 5 years (with the exception of localized basal cell, squamous cell skin cancer, or in situ cancer that has been resected).
4. Subject has adjusted (increased or decreased by +/-30%) dosage (in MEDD) of opioid treatment, has changed
opioid agents, or has changed route of opioid administration within 30 days of screening, or is likely to
discontinue or adjust dosage by +/-30% over the course of the study.
5. Subject has known or suspected anatomic or organic disorders of the large or small bowel; e.g.:
• Associated with a mechanical bowel obstruction (e.g., tumor, hernia, obstructive polyps), or pseudoobstruction;
• Associated with large or small bowel disorder such as ulcerative colitis or Crohn’s disease.
6. Subject has constipation that, according to the Investigator’s clinical judgment, is not the result of or not
exacerbated by opioid use, or is suffering from known or suspected secondary cause of constipation, including but not limited to: dietary disorders (e.g., malnutrition), neurologic disorders (e.g., spinal cord disorders), other congenital disorder, or endocrine disorders (e.g., hypothyroidism or diabetes).
7. Subject has impaired renal function identified at the Screening Visit (i.e., serum creatinine concentration > 1.8 mg/dL).
8. Subject has experienced an unexplained, clinically significant weight loss defined as > 5% weight loss within 90 days prior to the Screening Visit.
9. Subject has undergone a gastrointestinal or abdominal surgical procedure within 90 days prior to the Screening Visit, or has had a bowel resection at any time.
10. Subject is non-ambulatory.
11. Subject is unable to eat or drink, take oral medications, or to hold down oral medications due to vomiting.
12. Female subject of childbearing potential is unable or unwilling to use a protocol-specified method of birth control.
13. Female subject of childbearing potential has a positive screening pregnancy test, is currently pregnant or nursing, or plans to become pregnant or nurse during the clinical study.
14. According to Investigator’s clinical judgment, subject has clinically significant cardiovascular disease.
15. According to Investigator’s clinical judgment, subject has clinically significant, unexplained liver or lung disease, neurologic or psychiatric disorders (excluding depression), or any other systemic disease. If explained, the subject may be enrolled, if in the Investigator’s opinion, the condition would not interfere with safety or efficacy assessments, or result in an increased risk of participation to the subject.
16. Subject has a history of alcohol or drug abuse within 180 days prior to Screening Visit.
17. Subject demonstrates a potential for non-compliance with the study protocol (i.e., dosing schedule, visit schedule, diary completion, or study procedures).
18. Subject has participated in another study with an investigational drug, device, or procedure within the 30 days preceding the Screening Visit.
19. Subject has received AMITIZA®, lubiprostone, SPI-0211, or RU-0211 at any time prior to participation in this study.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be the overall SBM response rate. Responders, as defined in protocol Section 12.5.2, will be determined based on subjects' daily record of bowel movements. SBM is defined as any BM that does not occur within 24 hours after rescue medication use.

To summarize, patients will be required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM
frequency) for all treatment weeks for which observed data is available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks, in order to be defined as a treatment responder. This primary efficacy endpoint is designed to demonstrate consistent and durable relief from OBD.

E.5.1.1

Timepoint(s) of evaluation of this end point

Overall SBM response rate during 12-week treatment period.

E.5.2

Secondary end point(s)

• Change from baseline in SBM frequency
• First post-dose SBM (percentage of patients)
• Responder rates
• Mean changes from baseline in straining, stool consistency, constipation severity, abdominal bloating, abdominal discomfort, bowel habit regularity
• Treatment effectiveness
• Health related quality of life

E.5.2.1

Timepoint(s) of evaluation of this end point

Various timepoints specified for each secondary endpoint; generally assessed overall (over 12 weeks of treatment), unless otherwise specified.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Placebo-controlled

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Czech Republic

Germany

Poland

Sweden

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of trial is defined as the last visit of the last subject.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1