Clinical Trials Register

Summary
EudraCT Number:	2010-023915-33
Sponsor's Protocol Code Number:	PXL008-004
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-03-23
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2010-023915-33

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled, parallel-group study of the safety and efficacy of imeglimin or placebo add-on therapy in type 2 diabetic subjects not adequately controlled by sitagliptin monotherapy

A.3.1

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

Clinical study to asses whether the treatment with the drug imeglimin in combination with the drug sitagliptin in treatment of adult-onset sugar diabetes is safe and more effective than treatment with sitagliptin alone. The treatments will be assigned randomly and neither the patients nor their doctor will know what treatment is given, as those who will receive sitagliptin alone, for masking purposes, will also be given placebo - dummy tablets that look just like imeglimin.

A.4.1

Sponsor's protocol code number

PXL008-004

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	POXEL S.A.
B.1.3.4	Country	France
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	POXEL S.A.
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	POXEL S.A.
B.5.2	Functional name of contact point	Pascale Fouqueray
B.5.3	Address:
B.5.3.1	Street Address	200, avenue Jean Jaurès
B.5.3.2	Town/ city	Lyon
B.5.3.3	Post code	69007
B.5.3.4	Country	France
B.5.4	Telephone number	+33 6 98 01 71 03
B.5.5	Fax number	+33 4 37 70 88 15
B.5.6	E-mail	pascale.fouqueray@poxelpharma.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	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	imeglimin
D.3.2	Product code	PXL008
D.3.4	Pharmaceutical form	Tablet
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	imeglimin
D.3.9.2	Current sponsor code	PXL008
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	500 mg
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	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

E.1.1.1

Medical condition in easily understood language

adult-onset sugar diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10012607
E.1.2	Term	Diabetes mellitus inadequate control
E.1.2	System Organ Class	10027433 - Metabolism and nutrition 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 effect on glycemic efficacy using HbA1c as the primary evaluation criterion of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy

E.2.2

Secondary objectives of the trial

To assess the effect on other glycemic and non glycemic parameters of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy
To assess the safety and tolerability of 12-week treatment with imeglimin versus placebo add-on therapy in type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy
To assess imeglimin pre-dose concentration in the plasma at visits V7, V8 and V9 and 4-hour post-dose concentration at Visit 8

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusions criteria at Visit 1
• Subject has given written informed consent before any study-related activities are carried out
• Male or female type 2 diabetic subjects either
o Naïve of treatment with an HbA1c ≥ 8.5% and ≤ 10.5% or
o Inadequately controlled by metformin monotherapy at a dose ≥ 1500 mg/day with an HbA1c ≥ 7.5% and ≤ 10%
o Inadequately controlled by an alpha glucosidase inhibitor with an HbA1c and ≥ 8% and ≤ 10%
o Inadequately controlled by a sulfonylurea or glinide with an HbA1c ≥ 7.5% and ≤ 10%
• Age: ≥ 18 to ≤ 75 years
• Body Mass Index (BMI): ≥ 20 to ≤ 40 kg/m²
• No treatment with TZD or insulin (except short use of insulin in the dedicated context of a concomitant disease or surgery intervention) within 12 weeks before randomization
• Creatinine clearance as estimated by the MDRD formula: ≥ 60 ml/min
• Permitted concomitant medication stable for at least 14 days before randomization
• Effective contraception for women of child bearing potential

Inclusion criteria at Visit 6
• Subject has given written informed consent before any study-related activities are carried out
• Male or female type 2 diabetic subjects inadequately controlled by sitagliptin monotherapy (100 mg per day) as defined by HbA1c ≥ 7.5%
• Monotherapy with sitagliptin stable for at least 12 weeks before randomization
• HbA1c: ≥ 7.5% and ≤ 10%
• Age: ≥ 18 to ≤ 75 years
• Body Mass Index (BMI): ≥ 20 to ≤ 40 kg/m²
• No treatment with TZD or insulin (except short use of insulin in the dedicated context of a concomitant disease or surgery intervention) within 12 weeks before randomization
• Creatinine clearance as estimated by the MDRD formula: ≥ 60 ml/min
• Permitted concomitant medication stable for at least 14 days before randomization
• Effective contraception for women of child bearing potential

E.4

Principal exclusion criteria

• Any disease which in the investigator’s opinion would exclude the subject from the study
• Uncontrolled high blood pressure (BP): diastolic ≥ 95 mm Hg and systolic ≥ 160 mm Hg
• History of drug-induced Torsade de Pointe or presence of a familial long QT syndrome
• Impairment of hepatic function (alkaline phosphatase [AP], aspartate aminotransferase [AST] or alanine aminotransferase [ALT] ≥ 3 x the upper limit of normal)
• Pregnancy or lactation
• Mental handicap, legal incapacity, or any history of clinically important emotional and/or psychiatric illness
• Presence of a contraindication to the investigational medication, including sitagliptin
• Known hypersensitivity to any of the constituents or excipients of the study drug or history of relevant drug and/or food allergy (anaphylactic, anaphylactoid reactions)
• Evidence of retinopathy of severity ≥35 in the Classification of Retinopathy Severity (as defined by the Early Treatment Diabetic Retinopathy Study and outlined in Appendix II) assessed by an ophthalmologist within 12 months before randomization.
• Change in currently used medication and/or use of any new prescription or non-prescription medication within 14 days prior to randomization. The occasional use of paracetamol is authorized
• Positive screen for hepatitis B surface antigen (HbsAg), antibody to the hepatitis A virus (Anti-HAV Immunoglobulin M), antibody to the hepatitis C virus (Anti-HCV), or antibodies to human immunodeficiency (Anti-HIV) 1 and 2 virus at screening
• Any history of alcohol abuse or drug addiction
• Participation in a clinical study within 60 days before randomization
• Donation of blood within 30 days before randomization

E.5 End points

E.5.1

Primary end point(s)

The primary assessment of efficacy will be made based on the change in HbA1c between Visit 6 (Baseline) and Visit 9 (Week 12). HbA1c will be measured from fasting blood samples collected at these time points. This parameter will be assessed both using the ITT and the PP populations and by LOCF and observed cases.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to week 12

E.5.2

Secondary end point(s)

HbA1c responder (Yes/No): defined as HbA1c ≤ 7.0% at Week 12
- Change from baseline to Week 12 in fasting plasma glucose, insulin and c-peptide
- Change from baseline to Week 12 in homeostasis model of insulin resistance and beta-cell function (HOMA-IR and HOMA-B)
- Change from baseline to Week 12 in pro-insulin/insulin ratio
- Change from baseline to Week 12 in total cholesterol, HDL-C and LDL-C
- Change from baseline to Week 12 in triglycerides
- Change from baseline to Week 12 in hsCRP, fibrinogen.
- Percentage of subjects requiring rescue therapy any time between receiving first dose and Week 12.

E.5.2.1

Timepoint(s) of evaluation of this end point

On V1, HbA1c, fasting plasma glucose, insulin and c-peptide, total cholesterol, triglycerides and hsCRP. On V3, V4 and V5: fasting plasma glucose and HbA1c. On V6 and V9: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Apo B, hsCRP, fibrinogen. On V7: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, triglycerides and hsCRP. On V8: HbA1c, fasting plasma glucose and insulin, pro-insulin and c-peptide, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and hsCRP. On V10: fasting plasma glucose, insulin and c-peptide, triglycerides, hsCRP

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

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.8.2.4

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

Hungary

Latvia

Moldova, Republic of

Romania

Slovakia

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-Study is defined as the date of last visit of last subject undergoing 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

Number of subjects for this age range:

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.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

130

F.4.2.2

In the whole clinical trial

150

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)

normal treatment will be provided

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

2011-05-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-05-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-06-14

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