Clinical Trials Register

Summary
EudraCT Number:	2010-019343-20
Sponsor's Protocol Code Number:	654-002
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:	2010-10-07
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

2010-019343-20

A.3

Full title of the trial

A DOUBLE-BLIND, RANDOMISED, PARALLEL-GROUP STUDY TO COMPARE THE SAFETY AND EFFICACY OF TWO DOSE LEVELS OF OMS210 WITH PLACEBO IN THE TREATMENT OF PATIENTS WITH DIARRHOEA PREDOMINANT IRRITABLE BOWEL SYNDROME

A.3.1

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

A study to compare how safe and effective OMS210 with placebo is for the treatment of Irritable Bowel Syndrome

A.4.1

Sponsor's protocol code number

654-002

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	LOTUS PHARMA CO., LTD.
B.1.3.4	Country	Japan
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	LOTUS PHARMA CO., LTD.
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LOTUS PHARMA CO., LTD
B.5.2	Functional name of contact point	Pharmaceutical Department
B.5.3	Address:
B.5.3.1	Street Address	2-15-1 Konan
B.5.3.2	Town/ city	Minato-ku, Tokyo
B.5.3.3	Post code	108-6028
B.5.3.4	Country	Japan
B.5.4	Telephone number	0081354237980
B.5.5	Fax number	0081367458498
B.5.6	E-mail	info210@lotus-ltd.co.jp

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	No
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	OMS210
D.3.4	Pharmaceutical form	Capsule
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	5-Chloro-2-(1,4-diazacycloheptan-1-y1)-7-methylbenzoxazole
D.3.9.1	CAS number	270917-08-3
D.3.9.2	Current sponsor code	OMS210
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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	No

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
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

Diarrhoea predominant irritable bowel syndrome

E.1.1.1

Medical condition in easily understood language

irritable bowel syndrome

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10048571
E.1.2	Term	Irritable bowel syndrome aggravated
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective of this study is:

· To determine the efficacy of OMS210 8 mg and 32 mg bid in the treatment of IBS-D
based on patient’s global response to treatment (improvement in IBS symptoms).

E.2.2

Secondary objectives of the trial

Secondary objectives of this study are:

· To compare OMS210 8 mg and 32 mg bid with placebo based on:
· Improvement in abdominal pain/discomfort
· Change from baseline in assessment of IBS symptoms
· Change from baseline in abdominal pain/discomfort
· Change from baseline in bloating/distension
· Change from baseline in urgency
· Change from baseline in Bristol Stool Scale score
· Improvement in quality of life (QOL) as measured by IBS quality of life
(IBS-QOL) total score
· To characterise the PK in patients with IBS-D.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient will be eligible for study participation if he/she meets the following criteria at both Visits 1 and 2:

1. Patient is male or female, aged 18 to 70 years, inclusive.

2. Patient has a diagnosis of IBS as defined by Rome III criterion. This criterion should be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. Recurrent abdominal pain or discomfort** at
least 3 days per month in the last 3 months associated with 2 or more of the following:
• Improvement with defecation; and/or
• Onset associated with a change in frequency of stool; and/or
• Onset associated with a change in form (appearance) of stool
** Discomfort means an uncomfortable sensation not described as pain

3. Patient has at least one of the following criteria indicative of the diarrhoea predominant sub-type of IBS:
• More than three bowel movements a day
• Loose (mushy) or watery stools (type 5, 6 or 7 on the Bristol Stool Scale)
• Urgency (having to rush to have a bowel movement)

4. Patient has none of the following criteria, indicative of the constipation predominant sub-type of IBS:
• Fewer than three bowel movements a week
• Hard or lumpy stools (type 1 or 2 on the Bristol Stool Scale)
• Straining during a bowel movement

5. Patient is considered to be in otherwise good health in the opinion of the investigator, as determined by: a medical history with no clinically significant abnormalities, a pre-study physical examination with no clinically significant abnormalities and pre-study clinical laboratory findings within normal range, or if outside the normal range, not deemed clinically significant in the opinion of the investigator.

6. Patient is using stable lifestyle and dietary measures for treating IBS prior to study entry and will be able to maintain these throughout the study (if applicable).

7. All females of child-bearing potential must have a negative serum pregnancy test immediately prior to enrolment. In addition, all females of child-bearing potential must agree to be completely abstinent or be using an accepted form of contraception throughout the entire study period. Accepted forms of contraception are defined as those with a failure rate of < 1% when properly applied and include: combination oral pill and some intra-uterine devices, as guided by the investigator plus usage by the male partner of a condom and spermicide. Female patients must also not be actively breast-feeding through the entire study period. For male subjects with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the follow-up visit. Adequate contraception is defined as the usage by the female partner of any form of hormonal contraception or intra-uterine device (which should be established prior to the start of the study), plus usage by
the male partner of a condom and spermicide. The failure rate of the applied contraception should be less then 1% when properly applied.

8. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects.

9. Patient has the ability to co-operate with the investigator and to comply with the requirements of the entire study.

10. Patient is able to understand and voluntarily sign and date written informed consent prior to inclusion in the study.

E.4

Principal exclusion criteria

A patient will not be eligible for study participation if he/she meets any of the exclusion criteria at Visit 1 and/or 2:

1. Patient has a known diagnosis of lactose intolerance or has had a previous positive hydrogen breath test (> 12 parts per million increase in hydrogen over fasting level).

2. Patient has any form of malabsorption, specifically celiac disease and exocrine pancreatic insufficiency of any aetiology.

3. Patient has any of the following red flag symptoms which are not typical of IBS: pain that awakens/interferes with sleep, diarrhoea that awakens/interferes with sleep, blood in the stool (visible or occult), weight loss, fever, clinically significant abnormal physical examination.

4. Patient has a history of lower GI bleeding in the last 2 years or has had an abnormal colonoscopy, flexible sigmoidoscopy, rectoscopy, anoscopy, protoscopy or abdominal ultrasound, unless further investigations have demonstrated a non-sinister cause.

5. Patient has uncontrolled or unstable abnormal thyroid function.

6. Patient has a positive test result for HIV, Hepatitis B or Hepatitis C at screening.

7. Patient has ongoing pelvic floor dysfunction or history of severe constipation or faecal impaction or required manual evacuation to accomplish bowel movement.

8. Patient reports having any Type 1 or Type 2 stool on the Bristol Stool Scale during the screening period.

9. History of bariatric surgery or colonic surgery at any time. Appendectomy and cholecystectomy are acceptable if uncomplicated (no peritonitis) but these procedures must not have been undertaken within 12 months of screening.

10. Female patient with ongoing endometriosis.

11. Family history of colorectal cancer within first-degree relatives. (If investigations performed within 12 months of screening did not reveal any evidence of malignancy or other safety concerns, then such patients may be enrolled)

12. History of severe adverse reaction or severe hypersensitivity reaction to any drug.

13. Significant history of drug/solvent/alcohol abuse as per investigator’s assessments

14. Patient has a positive stool culture or presence of ova or parasites in the stool at screening.

15. Patient has donated blood or blood products (e.g., plasma or platelets) within the 3 months prior to screening.

16. Significant infection or known inflammatory process at baseline or in the 4 weeks prior to screening

17. Patient has any clinically significant medical history or ongoing findings that may include but are not limited to malignant tumours, multiple (> 3 at the same time or on separate occasions) or advanced adenomas, inflammatory bowel disease, diverticulitis, ischemic colitis, lymphocytic colitis or collagenous colitis. Patients with diverticulosis may be included in the study provided their condition is stable and no clinically significant intervention for their condition has ever been required. Patients with mild to moderate anxiety and/or depression may be included in the study provided their condition is stable, inclusive of stable monotherapy.

18. Any other medical condition or investigations (including abnormal clinical laboratory tests) that in the Principal Investigator’s (PIs) opinion would make the administration of the study medication or study procedures hazardous to the patient or obscure the interpretation of AEs. Patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 2 x the upper limit of normal (ULN) must be excluded from the study.

19. Patient has participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.

20. Concurrent use of prohibited medication

21. Male patient who intends to father a child while participating in the study.

22. Prisoners or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a psychiatric or physical (e.g., infectious disease) illness will not be allowed enrolment into the study.

23. Patients with a clinically significant history of, unstable or clinically significant cardiovascular disease such as, but not limited to, ongoing cardiac arrhythmia, cardiac insufficiency, hypokalemia, long QT syndrome or family history of long QT syndrome or QTcF greater than 450 ms prior to enrolment (patients with uncomplicated, well controlled hypertension as judged by the Investigator, may be included).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study will be the proportion of responders in each treatment group, where a responder is defined as a patient who has a positive change from baseline of ≥ 1 point in self-reported assessment if IBS symptoms as measured by a 7-point Likert scale after 4 weeks of treatment.

E.5.2

Secondary end point(s)

• To compare OMS210 8 mg and 32 mg bid with placebo based on:
• Improvement in abdominal pain/discomfort
• Change from baseline in assessment of IBS symptoms
• Change from baseline in abdominal pain/discomfort
• Change from baseline in bloating/distension
• Change from baseline in urgency
• Change from baseline in Bristol Stool Scale score
• Improvement in quality of life (QOL) as measured by IBS-QOL total score
• To characterise the pharmacokinetics (PK) in patients with IBS-D.

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

The end of the study will be defined as the last visit of the last patient in the study.

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