Clinical Trials Register

Summary
EudraCT Number:	2010-021397-12
Sponsor's Protocol Code Number:	M0003-C202
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-09-14
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

Germany - BfArM

A.2

EudraCT number

2010-021397-12

A.3

Full title of the trial

An explorative, randomized, placebo-controlled, double-blind, parallel-group trial, to evaluate the pharmacodynamic effect of M0003 on reflux parameters in subjects with gastroesophageal reflux disease and with persistent symptoms despite taking a stable dose of proton pump inhibitors.

A.4.1

Sponsor's protocol code number

M0003-C202

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Shire-Movetis NV
B.1.3.4	Country	Belgium
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	M0003
D.3.2	Product code	M0003
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	219984-49-3
D.3.9.2	Current sponsor code	M0003
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	to 0.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Tablet
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

Gastrointestinal esophageal reflux disease (GERD) refractory to proton pump inhibitor therapy

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10017885
E.1.2	Term	Gastrooesophageal reflux disease

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

This is an exploratory trial :
1. To measure the pharmacodynamic (PD) effect on parameters derived from 24-h pH/impedance (MII) monitoring,
2. To explore the effect on symptoms,
3. To evaluate the safety and tolerability

of treatment with 0.5 mg M0003 (on top of PPI treatment), t.i.d. for 4 weeks, in subjects with GERD and with persistent symptoms despite taking a stable dose of proton pump inhibitors

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects who meet all of the following criteria are eligible for this trial:
1. Written ICF signed voluntarily before the first trial-related activity.
2. Aged between 18 and 70 years, extremes included.
3. Subjects with a history of GERD symptoms (i.e., heartburn and/or regurgitation)
during the last 6 months (as assessed by anamnesis/medical history).
4. Subjects on a stable dose of PPIs, compliant for at least 6 weeks prior to screening.
5. Subjects with heartburn and/or regurgitation, with at least one of these symptoms of moderate severity or worse, and at a minimum average frequency of three days a week during the two-week run-in period (determined by completion of a daily diary).
6. A minimum of 25 liquid-containing reflux events over 24 h (pH/MII monitoring).
7. BMI < 35.
8. If the subject is a woman of childbearing potential, she
a. must have a negative urine pregnancy test at screening and before the start of
treatment (minimum β-Human Chorionic Gonadotropin [HCG] sensitivity of 25 mIU/ml), and
b. must agree to either use an effective form of birth control (i.e., stabilized on oral
contraceptives for at least 1 month or using implanted, transdermal or injected
contraceptive hormones, an intra-uterine device, or continuous abstinence from
heterosexual sexual contact), or a combination of a barrier method and a spermicidal agent (i.e., cervical cap and spermicidal agent, condom and spermicidal agent, or diaphragm and spermicidal agent), until 30 days after the end of treatment, or until the onset of menses (last day of menses to be documented at screening, baseline visit and visit 6).
9. Endoscopy within the last 5 years prior to randomisation, negative for grade C & D
oesophagitis.

E.4

Principal exclusion criteria

Subjects meeting one or more of the following criteria cannot be selected:
1. History of cardiac arrhythmias, uncontrolled bronchospastic disease, cardiovascular
disease (e.g., ischemic heart disease or cerebrovascular accident), thyrotoxicosis.
2. Subjects with a family history of sudden death or a congenital QT syndrome.
3. Presence of prolonged QTc (Bazett and Fridericia) on ECG at screening (QTc ≥ 450
msec for males and QTc ≥ 470 msec for females).
4. Subjects with a documented history of long segment (>3 cm) Barrett’s oesophagus.
5. Subjects with documented or suspected large (> 3 cm) hiatus hernia.
6. Subjects with fundoplication, endoscopic anti-reflux procedure or major prior GI
surgery.
7. Subjects with clinically significant abnormalities as judged by the investigator at
screening physical examination, or in blood haematology and biochemistry tests
performed at screening.
8. Subjects with a structural abnormality or structural disease condition of the GI tract.
9. Severe oesophageal motility disorders (e.g., scleroderma, achalasia, nutcracker
oesophagus).
10. Subjects who suffer from frequent vomiting (>1/week, as assessed during
anamnesis).
11. Current diagnosis of co-existing psychiatric disease (including alcohol or drug
abuse); controlled depression and anxiety are allowed, when treated with at most
one drug, at a stable dose.
12. Subjects suffering from severe and/or uncontrolled endocrine (e.g., insulindependent diabetes mellitus, hypopituitarism, hypothyroidism, hypercalcaemia,
pseudohypopara-thyroidism), metabolic (e.g., porphyria, hypokalaemia, amyloidal
neuropathy) and neurologic diseases (e.g., Parkinson’s disease, multiple sclerosis,
meningocele, aganglionosis, hypoganglionosis, hyperganglionosis, autonomic neuropathy, spinal cord injury, Chagas’ disease, major depression). Endocrine and
metabolic disorders controlled by appropriate medical therapy will not be excluded,
except for insulin-dependent diabetes mellitus.
13. Presence of severe and clinically uncontrolled cardiovascular, liver or lung disease,
neurologic, cancer or AIDS.
14. Alarm symptoms suggestive of malignancies or organic disease such as: obstructive dysphagia, odynophagia, GI bleeding, blood in stool or anaemia, weight loss; unless investigated and found to be negative.
15. Impaired renal function, i.e., serum creatinine concentration >2 mg/dl (>180 μmol/l).
16. Use of prohibited co-medication less than 7 days before the start of the 2-week runin period (baseline symptom assessment).
17. Any condition that, in the opinion of the Investigator(s), would complicate or
compromise the trial (e.g., human immunodeficiency virus [HIV] infection,
gastroduodenal ulcer) or the well-being of the subject, or evidence of any clinically
relevant pathology that could interfere with trial results or put subject safety at risk.
18. Participation in an investigational drug trial in 30 days prior to enrolment.
19. Breast-feeding subjects.

E.5 End points

E.5.1

Primary end point(s)

This is an exploratory trial.

• the number of liquid-containing reflux events per 24-h period;
• the average proximal extent of all liquid-containing reflux events in the 24-h period;
• average bolus clearance times of all liquid-containing reflux events in the 24-h
period;

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

tolerability

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

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.8.3

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Yes

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 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	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	14
F.4.2	For a multinational trial
F.4.2.1	In the EEA	80
F.4.2.2	In the whole clinical trial	100

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-12-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-01-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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