Clinical Trials Register

Summary
EudraCT Number:	2007-000486-38
Sponsor's Protocol Code Number:	SYR-322_301
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-05-29
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

Netherlands - Competent Authority

A.2

EudraCT number

2007-000486-38

A.3

Full title of the trial

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study
Comparing SYR-322 Alone and Combination SYR-322 with Pioglitazone versus Placebo on Postprandial Lipids in Subjects with Type 2 Diabetes

A.3.2

Name or abbreviated title of the trial where available

Post-Prandial

A.4.1

Sponsor's protocol code number

SYR-322_301

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	Takeda Global Research & Development Centre (Europe) Ltd.,
B.1.3.4	Country	United Kingdom
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	SYR-322 (SYR110322)
D.3.2	Product code	SYR-322_301
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.3.9.2	Current sponsor code	SYR-322_301
D.3.9.3	Other descriptive name	SYR-322 (SYR110322)
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	25
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.IMP: 2
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	Actos 30 mg Tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Global Research & Development Centre (Europe) Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Actos
D.3.2	Product code	Pioglitazone
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.3.8	INN - Proposed INN	Pioglitazone Hydrochloride
D.3.9.3	Other descriptive name	Pio
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	30
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

Type 2 diabetes mellitus

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	10045242
E.1.2	Term	Type II diabetes mellitus

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 effects of SYR-322 alone and SYR-322 coadministered with pioglitazone HC1 versus placebo on postprandial triglycerides in subjects with type 2 diabetes.

E.2.2

Secondary objectives of the trial

To evaluate the effect of SYR-322 and SYR-322 coadministered with pioglitazone HC1 versus placebo on postprandial lipid parameters, postprandial lipoprotein parameters, postprandial GLP-1, postprandial glucagon, postprandial glucose, postprandial insulin, measurements of glycemic control (ie, A1C, fasting plasma glucose, C-peptide, insulin, proinsulin), inflammatory markers (ie, adiponectin and high-sensitivity C-reactive protein), cardiovascular markers (ie, VCAM, ICAM, and e-selectin), and endothelial function (pulse wave tonometry). Safety variables will include incidence of treatment emergent adverse events (AEs), clinical laboratory evaluations, physical examinations, vital signs, and 12-lead ECG readings.

In addition markers of oxidative stress and short term glycaemic control will be evaluated as exploratory variables.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject eligibility is determined according to the following criteria:
1. The subject is male or female, with a historical diagnosis of type 2 diabetes, and must be aged 18 to 70 years, inclusive.

2. A female subject of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study. Women NOT of child bearing potential are defined as those who have been surgically sterilized (hysterectomy, oophorectomy, tubal ligation) or who are post-menopausal (defined as at least 2 years since last regular menses). Acceptable methods of contraception are defined in Section 9.1.11 Contraception and Pregnancy Avoidance Procedure.

3. The subject is capable of understanding and complying with the protocol requirements.

4. The subject has either failed treatment with diet and exercise for 3 months prior to Screening or has been receiving a stable dose of metformin, sulfonylurea, nataglinide, or repaglinide for more than 3 months prior to Screening.

5. The subject has inadequate glycemic control as defined by A1C concentration between 6.5 and 9.0%, inclusive.

6. The subject has a fasting plasma glucose <13.3 mmol/L.

7. The subject has a fasting serum triglyceride level of 1.7 to 5.0 mmol/L, inclusive.

8. The subject has not been receiving any lipid-lowering therapy within 3 months prior to Screening or on a stable statin and/or ezetimibe therapy (same drug and dose) for at least 3 months.

9. The subject has a body mass index >23 kg/m2 and <45 kg/m2.

10. If the subject has regular use of other, nonexcluded medications, subject must be on a stable dose for at least 4 weeks prior to Screening. Use of PRN (as needed) prescription medications and over-the-counter medications is allowed at the discretion of the investigator.

11. The subject or subject’s legally authorized representative signs a written informed consent prior to the initiation of any study procedures.

12. The subject is to be Apolipoprotein E 3/3 or Apolipoprotein E 3/4 phenotype positive prior to baseline

E.4

Principal exclusion criteria

Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has a history of type 1 diabetes.

2. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.

3. The subject has a diastolic blood pressure greater than 100 mm Hg or a systolic blood pressure of greater than 160 mm Hg.

4. The subject has a previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)

5. The subject has a hemoglobin <120 g/L for males and <100 g/L for females.

6. The subject has an alanine transaminase (ALT) level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.

7. The subject has a serum creatinine level >133 μmol/L.

8. The subject has a fasting total cholesterol >6.5 mmol/L.

9. The subject has New York Heart Association heart failure of any Class (I-IV)
regardless of therapy.

10. The subject has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.

11. The subject has a history of acute metabolic diabetic complications.

12. The subject has a history of any hemoglobinopathy that may affect determination of A1C.

13. The subject has a history of infection with human immunodeficiency virus.

14. The subject has a history of diabetic gastro paresis.

15. The subject has a history of gastric bypass surgery.

16. The subject is unwilling or unable to comply with the protocol or scheduled appointments.

17. The subject has a history of hypersensitivity or allergies to SYR-322, pioglitazone or any related compounds.

18. The subject is pregnant, intends to become pregnant during the course of the study, or is lactating.

19. The subject is currently participating in another investigational study or has participated in an investigational study within the past 30 days.

20. The subject has any other serious disease or condition at Screening or at randomization that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change from Baseline in postprandial incremental area under the curve (AUC) for triglycerides at Week 16.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment.

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

2008-05-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-07-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-12-17

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