Clinical Trials Register

Summary
EudraCT Number:	2008-001064-37
Sponsor's Protocol Code Number:	S348.2.001
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:	2008-06-27
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

2008-001064-37

A.3

Full title of the trial

Effect of Choline Fenofibrate (ABT-335 /SLV348) on Macular Edema Measured by Optical Coherence Tomography in Subjects with Diabetic Macular Edema - a one-year, Placebo-Controlled, Randomized Study

A.4.1

Sponsor's protocol code number

S348.2.001

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	Fournier Laboratories Ireland
B.1.3.4	Country	Ireland
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	Choline Fenofibrate
D.3.2	Product code	ABT-335/SLV348
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.2	Current sponsor code	ABT-335/SLV348
D.3.9.3	Other descriptive name	Choline fenofibrate
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	135
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	Capsule, hard
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

Diabetic macular edema

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10057934
E.1.2	Term	Diabetic macular edema

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 evaluate the effect of choline fenofibrate on the course of macular edema in eyes of subjects with type 2 diabetes mellitus (T2DM) presenting with diabetic macular edema (DME) with or without center involvement. The primary criterion will be change in Total Macular Volume (TMV) between baseline and endpoint in the choline fenofibrate, adjusted on the change in placebo.

E.2.2

Secondary objectives of the trial

To evaluate the effects of choline fenofibrate on the other OCT (Optical Coherence Tomography) parameters, on macular edema grading, on hard exudate grading, on visual acuity, on Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy grading and on need for laser photocoagulation.

To evaluate the safety of choline fenofibrate in diabetic patients presenting with DME.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject will be eligible for study participation if he/she meets the following criteria:

1. Subject has voluntarily signed and dated an ICF, approved by an IEC, after the nature of the study has been explained and the subject has had the opportunity to ask questions and receive answers. The informed consent must be signed at the Pre-screening Visit, prior to any study-specific procedures.

2. Subject is ≥ 30 years of age and either gender at the time of the Pre-screening Visit.

3. Subject has been diagnosed with T2DM for at least 6 months before the Pre-screening Visit. Any of the following will be considered to be sufficient evidence that diabetes is present:
a. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes;
b. Current regular use of insulin for the treatment of diabetes;
c. Documented diabetes according to American Diabetes Association and/or World Health Organisation (WHO) criteria.

4. Subject is diagnosed with DME in at least one eye with any appropriate investigational method (i.e. slit lamp biomicroscopy or stereoscopic fundus photography) when laser photocoagulation can be safely postponed by at least 3 months in the investigator’s opinion.

5. Subject has at least one eligible eye on OCT assessment performed with standardized operation procedures and materials i.e. OCT3 (mapping software, version 4.0 or above from the Stratus® OCT, reference of standard OCT protocol of ETDRS study, 9 regions/subfields) and centrally read which is defined as thickness of ≥ 300 µm in at least one of the 5 following zones: center zone, superior inner zone, nasal inner zone, inferior inner zone, temporal inner zone. Each eligible eye will be classified as:
a. With center involvement: center zone thickness ≥ 250 µm;
b. Without center involvement: center zone thickness < 250 µm.

6. Subject has, in the opinion of the investigator, a life expectancy greater than one year at the Pre-screening Visit.

7. Subject has documented elevated TG levels (TG ≥89 mg/dL [1.00 mmol/L]) at the Screening Visit or in the previous 3 months (in case of concomitant lipid-lowering treatment with a fibrate this criterion is verified after a minimum 4 week wash-out at visit 2).

8. If female, subject is either postmenopausal for at least one year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or of childbearing potential with negative results of a serum pregnancy test performed at the Screening Visit and she must agree to practice one of the following methods of birth control for the duration of the study:
a. total abstinence from sexual intercourse (minimum one complete menstrual cycle, prior to study drug administration);
b. a vasectomized partner;
c. hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration;
d. intrauterine device (IUD); or
e. double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or creams).

9. Subject is not breastfeeding at the Pre-screening Visit and at any time during the study.

10. Subject must be willing to participate in the study and to complete all the scheduled assessments.

E.4

Principal exclusion criteria

Any eye of the subject will be excluded in presence of any of the following criteria:

1. Has been treated with vitrectomy at any time, cataract extraction or scatter laser photocoagulation in the last 6 months or macular laser photocoagulation in the last 4 months.

2. Retinal thickening results from epiretinal membranes or vitreomacular traction.

3. Macular edema is considered to be due to a cause other than DME i.e. related to ocular surgery.

4. Eye is likely, in the investigator’s opinion, to receive scatter photocoagulation or photocoagulation for high risk PDR, capsulotomy, major ocular surgery including cataract extraction or intra-vitreal injection of anti inflammatory or/and anti VEGF agents in the next 6-12 months.

5. Definite glaucoma, but ocular hypertension alone will not be an exclusion criterion.

6. Has been previously enrolled in any study using intra-vitreal investigational product (e.g. steroids or antiVEGF) within 6 months of the Screening Visit.

7. Poor visual acuity: 20/800 (i.e. ETDRS visual acuity score 3 letters) or worse.

The subject will be excluded from the study if he/she meets any of the following criteria:

8. Unwilling or unable to consent to enter the study.

9. History of an allergic reaction or hypersensitivity to fenofibrate or ABT-335 /SLV348 or its inactive ingredients, or known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.

10. Used any investigational drug within 8 weeks of the Screening Visit.

11. Uncontrolled T2DM defined as HbA1c of > 10%.

12. Systolic blood pressure (SBP) measurement of > 160 mmHg and/or a diastolic blood pressure (DBP) measurement of > 90 mmHg at the screening or baseline visits.

13. History of pancreatitis or gall bladder disease, but subjects with gall bladder disease who have previously undergone a cholecystectomy will be allowed to enroll.

14. History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.

15. History of gastric or duodenal ulcer within 3 months of the Pre-screening Visit.

16. Significant history of oncologic, hematologic, gastrointestinal, hepatic, or a neurological disorder (cerebrovascular disease, degenerative disease) that would limit study evaluation or participation.

17. Currently ongoing hepatitis B or hepatitis C.

18. Evidence of unstable or severe cardiovascular disease:
a. Myocardial infarction, coronary bypass surgery, or angioplasty within 3 months of the Pre-screening Visit;
b. Unstable angina pectoris or uncontrolled cardiac arrhythmias within 3 months prior to the Pre-screening Visit;
c. Severe peripheral artery disease as evidenced by critical limb ischemia within 3 months of the Pre-screening Visit;
d. Major peripheral artery surgery (e.g. femoral-popliteal revascularization, abdominal aortic aneurysm repair, etc.) within 3 months of the Pre-screening Visit.

19. Symptomatic heart failure (class III or IV of the New York Heart Association).

20. History of diagnosed hereditary or acquired myopathy.

21. Received a solid organ transplant.

22. Known to be human immunodeficiency virus positive.

23. History of mental instability, recreational drug or alcohol abuse or subject has been treated for severe psychiatric illness, which, in the opinion of the investigator, may interfere with optimal participation in the study.

24. Has initiated, discontinued or changed dosage of hormone therapy, including estrogen, progesterone, testosterone and/or thyroid hormone supplementation therapy, within 8 weeks of the Pre-screening Visit.

25. Is receiving coumarin anticoagulants, systemic cyclosporine, oral corticosteroids or is planned to receive corticosteroid intra-vitreal injection in the next 3 months.

26. Laboratory analyses, performed at the Screening Visit, show any of the following results:
a. Alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or total bilirubin concentration > 1.5 ×Upper Limit of Normal (ULN);
b. Creatine kinase (CK) level > 3.0 ×ULN;
c. Estimated glomerular filtration rate (eGFR) (with Modification of Diet in Renal Disease equation) < 30 ml/min/1.73 m2;
d. TG > 500 mg/dL [5.6 mmol/L]

27. Is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

E.5 End points

E.5.1

Primary end point(s)

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)

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

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

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	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	Information not present in EudraCT
F.4 Planned number of subjects to be included
F.4.1	In the member state	12
F.4.2	For a multinational trial
F.4.2.1	In the EEA	106
F.4.2.2	In the whole clinical trial	106

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

2008-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-08-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-03-21

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