Clinical Trials Register

Summary
EudraCT Number:	2017-002309-36
Sponsor's Protocol Code Number:	PDY15010
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-11-06
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

2017-002309-36

A.3

Full title of the trial

A randomized, double-blind, parallel-group, 2-treatment multiple dose study to assess the intestinal, metabolic and cardiovascular effects of an 8 weeks treatment with sotagliflozin QD as compared with empagliflozin QD in T2DM patients with mild to moderate hypertension

A.3.1

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

Comparison of Pharmacodynamic Effects of Sotagliflozin and Empagliflozin in T2DM Patients with Mild to Moderate Hypertension

A.4.1

Sponsor's protocol code number

PDY15010

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1186-2962

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	SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
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	SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
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	Sanofi-Aventis Deutschland GmbH
B.5.2	Functional name of contact point
B.5.3.4	Country	Germany
B.5.6	E-mail	medinfo.de@sanofi.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	Sotagliflozin
D.3.2	Product code	SAR439954
D.3.4	Pharmaceutical form	Film-coated 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	SOTAGLIFLOZIN
D.3.9.1	CAS number	1018899-04-1
D.3.9.2	Current sponsor code	SAR439954
D.3.9.4	EV Substance Code	SUB179285
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	200
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Jardiance
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
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	Jardiance
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	Empagliflozin
D.3.9.1	CAS number	864070-44-0
D.3.9.3	Other descriptive name	EMPAGLIFLOZIN
D.3.9.4	EV Substance Code	SUB35915
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)	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
D.8 Placebo: 2
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

Diabetes mellitus

E.1.1.1

Medical condition in easily understood language

Diabetes mellitus

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10012601
E.1.2	Term	Diabetes mellitus
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 compare the metabolic and gastrointestinal pharmacodynamic (PD) effects of an 8 weeks treatment with sotagliflozin once daily (QD) to an 8 weeks treatment to empagliflozin QD in mild or moderate hypertensive T2DM patients on a stable treatment regimen with metformin and an angiotensin converting enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) under standardized diet conditions.

E.2.2

Secondary objectives of the trial

-To compare the renal and cardiovascular PD effects of an 8 weeks treatment with sotagliflozin QD to an 8 weeks treatment to empagliflozin QD in mild or moderate hypertensive T2DM patients on a stable treatment regimen with metformin and an ACE inhibitor or ARB.
-To evaluate the safety and tolerability of an 8 weeks QD treatment with sotagliflozin or empagliflozin in mild to moderate hypertensive T2DM patients on a stable treatment with metformin and an ACE inhibitor or ARB.
-To evaluate the pharmacokinetic (PK) profile of sotagliflozin in steady state conditions.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Male or female patients with Type 2 Diabetes Mellitus (T2DM)
(diagnosed at least 1 year before screening visit), between 18 and 74 years of age, inclusive, with:
-Hypertension grades 1 or 2 as defined by the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) at screening; SBP (systolic blood pressure) has to be in the range of 140-179 mmHg (after 10 minutes resting in supine position, measurement in triplicate with each measurement to be within this range at screening). If the
blood pressure (BP)range is not met at screening, one repeat
measurement at another occasion is allowed prior to inclusion into the study.
-Glycated Haemoglobin A1c (HbA1c) at screening between 6.5% and 11%.
-On a stable treatment with metformin, ie, no change in dose regimen or in dose levels in the last 3 months prior to screening and until randomization.
-On a stable treatment with an ACE inhibitor or an angiotensin receptor blocker after switching from beta-blockers and/or thiazides for eligible patients after screening, ie, no change in dose regimen and in dose levels in the last 4 weeks prior to run-in phase and until randomization
-Body weight between 50.0 kg and 130 kg, inclusive, if male, and
between 40.0 kg and 110 kg, inclusive, if female, body mass index
between 18.0 and 38.0 kg/m2, inclusive.
-Kidney function: Estimated glomerular filtration rate at screening must be 60 mL/min/1.73m2 or higher.

E.4

Principal exclusion criteria

-Patients with severe anemia, severe cardiovascular, gastrointestinal,respiratory, neurological, osteomuscular, psychiatric, or active malignant tumor or other major systemic disease or patients with infectious disease, signs of acute illness, or short life expectancy making implementation of the protocol or interpretation of the study results
difficult (as evaluated by detailed medical history and complete physical
and laboratory examination).
-Heart failure New York Heart Association (NYHA) Classification III/IV.
-Any clinically significant abnormality in echocardiography performed at
screening as judged by the investigator based on age, gender and
medical history of the individual patient.
-History of myocardial infarction within the last 12 months prior to
screening.
-Likelihood of requiring treatment during the study period with drugs
not permitted by the study protocol (e.g., long-term systemic
glucocorticoids) and refusing or unable to take alternative treatment.
-Type 1 diabetes mellitus.
-Secondary hypertension of any etiology (eg, renovascular disease,
pheochromocytoma, Cushing's syndrome).
-Clinically significant pulmonary hypertension, in particular World Health
Organisation (WHO) Classes IV (Pulmonary hypertension due to chronic
thrombotic and/or embolic disease [CTEPH]) and V (miscellaneous).
-Diabetic retinopathy.
-History of diabetic ketoacidosis or non-ketotic hyperosmolar coma
within 12 weeks prior to the Screening Visit.
-History of severe hypoglycemia resulting in hospitalization or
unconsciousness/seizures within 6 months prior to the Screening visit.
-History of prior gastric or intestinal surgical procedure including gastric
banding within 3 years before the Screening Visit. Any gastrointestinal
surgery with removal of part of the bowels or the stomach
-History of unexplained pancreatitis, chronic pancreatitis,
stomach/gastric surgery, inflammatory bowel disease.
-Known hypersensitivity to sotagliflozin, empagliflozin or any excipient
of the drug products.

E.5 End points

E.5.1

Primary end point(s)

Assessment of pharmacodynamic (PD) parameters in feces
Assessment of PD parameters in urine
Assessment of PD parameters in blood

E.5.1.1

Timepoint(s) of evaluation of this end point

- Assessment of pharmacodynamic (PD) parameters in feces :
Baseline and on Day 55 and 56 (over 48 hours)

- Assessment of PD parameters in urine
Baseline and on Day 56 (over 24 hours)

- Assessment of PD parameters in blood
Baseline and on Day 56

E.5.2

Secondary end point(s)

1 - Fasting metabolic laboratory panel
2 - Ambulatory Blood Pressure Measurement (ABPM)
3 - Cardiovascular parameters
4 - Pulse wave velocity
5 - Continuous Glucose Monitoring (CGM)
6 - Echocardiography
7 - Plasma Volume Measurement
8 - Adverse events
9 - Assessment of pharmacokinetic (PK) parameters: Cmax
10 - Assessment of pharmacokinetic (PK) parameters: Ctrough
11 - Assessment of pharmacokinetic (PK) parameters: AUCtau
12 - Assessment of pharmacokinetic (PK) parameters: tmax

E.5.2.1

Timepoint(s) of evaluation of this end point

1 - Fasting metabolic laboratory panel : Baseline and on Day 56
2 - Ambulatory Blood Pressure Measurement (ABPM) : Baseline and on days 54 until Day 56
3 - Cardiovascular parameters : Baseline and on Day 56
4 - Pulse wave velocity : Baseline and on Day 55
5 - Continuous Glucose Monitoring (CGM) : Baseline, last 3 days of treatment
6 - Echocardiography : Baseline and on Day 54
7 - Plasma Volume Measurement : Baseline and on Day 54
8 - Adverse events : Over 15 weeks

24 hours after IMP administration
9 - Assessment of pharmacokinetic (PK) parameters: Cmax
10 - Assessment of pharmacokinetic (PK) parameters: Ctrough
11 - Assessment of pharmacokinetic (PK) parameters: AUCtau
12 - Assessment of pharmacokinetic (PK) parameters: tmax

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

E.6.6

Pharmacokinetic

Yes

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

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)

Yes

E.8.2.2

Placebo

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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 Subject Last Visist (LSLV)

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 months

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.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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)

After end of this clinical study, the further Treatment of the patients will be performed by their HCP.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-02-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-18

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