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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00976937




Registration number
NCT00976937
Ethics application status
Date submitted
14/09/2009
Date registered
15/09/2009
Date last updated
11/10/2016

Titles & IDs
Public title
24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
Scientific title
A Randomized, Double-blind, Double-dummy, 2-arm Parallel-group, Multicenter 24-week Study Comparing the Efficacy and Safety of AVE0010 to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 and Not Adequately Controlled With Metformin
Secondary ID [1] 0 0
EudraCT:2008-007 334-22
Secondary ID [2] 0 0
EFC10780
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lixisenatide (AVE0010)
Treatment: Drugs - Lixisenatide Placebo
Treatment: Drugs - Sitagliptin
Treatment: Drugs - Sitagliptin Placebo
Treatment: Drugs - Metformin

Experimental: Lixisenatide - 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24.

Active comparator: Sitagliptin - Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.


Treatment: Drugs: Lixisenatide (AVE0010)
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Treatment: Drugs: Lixisenatide Placebo
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Treatment: Drugs: Sitagliptin
Administered orally once a day in the morning with or without food at approximately the same time each day.

Treatment: Drugs: Sitagliptin Placebo
Administered orally once a day in the morning with or without food at approximately the same time each day.

Treatment: Drugs: Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Absolute Change From Baseline in HbA1c at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline in Body Weight at Week 24
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change From Baseline in Glucose Excursion at Week 24
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment-Beta (HOMA-beta) at Week 24
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Percentage of Patients Requiring Rescue Therapy During 24-Week Period
Timepoint [13] 0 0
Baseline up to Week 24

Eligibility
Key inclusion criteria
Inclusion criteria

* Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/day (g/day) for at least 3 months prior to the screening visit
* Patients with obesity (BMI greater than equal to [>=] 30 kg/m^2) and aged from 18 years to less than 50 years
Minimum age
18 Years
Maximum age
49 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

* HbA1c less than (<) 7.0 percent (%) or HbA1c greater than (>) 10% at screening
* Type 1 diabetes mellitus
* Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
* FPG at screening >250 milligram/deciliter (mg/dL) (>13.9 millimole/ liter [mmol/L])
* Weight change of more than 5 kg during the 3 months preceding the screening visit
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes)
* History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
* Hemoglobinopathy or hemolytic anemia or receipt of blood or plasma products within 3 months prior to the time of screening
* Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
* Known history of drug or alcohol abuse within 6 months prior to the time of screening
* Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG) or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator could have precludes safe completion of the study or constrains efficacy assessment such as major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure >180 millimeter of mercury (mmHg) or >110 mmHg, respectively
* Laboratory findings at the time of screening : Amylase and/or lipase >3 times the upper limit of normal (ULN) laboratory range; alanine aminotransferase (ALT): >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb), positive serum pregnancy test in females of childbearing potential, and calcitonin >=20 picogram per milliliter (pg/mL) (5.9 picomole per liter)
* Patients who are considered by the investigator or any sub-investigator as inappropriate for the study for any reason (for example, impossibility to meet specific protocol requirements [such as scheduled visits, being able to do self-injections], likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol, investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
* Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, dipeptidyl peptidase IV (DPP-IV) inhibitors, insulin) within 3 months prior to the time of screening
* History of bariatric surgery, anti-obesity treatment, or unstable diet within 3 months prior to the time of screening
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
* Use of any investigational drug within 3 months prior to screening
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
* Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)
* Allergic reaction to any glucagon like peptide-1 (GLP 1) agonist in the past (for example, exenatide, liraglutide) or to metacresol
* History of a serious hypersensitivity reaction to sitagliptin
* Moderate or severe renal impairment (creatinine clearance inferior to 50 milliliter/minute [mL/min])
* Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in period (>2 injections missed or >2 capsules missed); and patient with any adverse event which could have precludes the inclusion in the study, as assessed by the investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2011
Sample size
Target
Accrual to date
Final
319
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Investigational Site Number 036006 - Adelaide
Recruitment hospital [2] 0 0
Sanofi-Aventis Investigational Site Number 036001 - Box Hill
Recruitment hospital [3] 0 0
Sanofi-Aventis Investigational Site Number 036004 - Elizabeth Vale
Recruitment hospital [4] 0 0
Sanofi-Aventis Investigational Site Number 036002 - Geelong
Recruitment hospital [5] 0 0
Sanofi-Aventis Investigational Site Number 036005 - Meadowbrook
Recruitment hospital [6] 0 0
Sanofi-Aventis Investigational Site Number 036003 - Sydney
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment postcode(s) [5] 0 0
4131 - Meadowbrook
Recruitment postcode(s) [6] 0 0
2006 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
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Michigan
Country [9] 0 0
United States of America
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Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Brazil
State/province [16] 0 0
Belem
Country [17] 0 0
Brazil
State/province [17] 0 0
Brasilia
Country [18] 0 0
Brazil
State/province [18] 0 0
Caxias Do Sul
Country [19] 0 0
Brazil
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Curitiba
Country [20] 0 0
Brazil
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Rio De Janeiro
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Brazil
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Sao Paulo
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Canada
State/province [22] 0 0
Calgary
Country [23] 0 0
Canada
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Hamilton
Country [24] 0 0
Canada
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London
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Canada
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Montreal
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Canada
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Oakville
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Canada
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St-Romuald
Country [28] 0 0
Canada
State/province [28] 0 0
Thornhill
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Canada
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Toronto
Country [30] 0 0
Canada
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Vancouver
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Canada
State/province [31] 0 0
Victoria
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Chile
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Santiago
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Germany
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Berlin
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Germany
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Ludwigshafen
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Germany
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Schkeuditz
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Guatemala
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Guatemala
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Mexico
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Aguascalientes
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Mexico
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Chihuahua
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Mexico
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Df
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Mexico
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Merida
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Mexico
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México City
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Mexico
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Pachuca
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Mexico
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Veracruz
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Mexico
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Zapopan
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Peru
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Lima
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Poland
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Bialystok
Country [47] 0 0
Poland
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Bydgoszcz
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Poland
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Warszawa
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Poland
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Wroclaw
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Romania
State/province [50] 0 0
Bacau
Country [51] 0 0
Romania
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Bucuresti
Country [52] 0 0
Romania
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Iasi
Country [53] 0 0
Romania
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Ploiesti
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Romania
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Resita
Country [55] 0 0
Romania
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Suceava
Country [56] 0 0
Romania
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Timisoara
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Kazan
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Russian Federation
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St-Petersburg
Country [59] 0 0
Russian Federation
State/province [59] 0 0
St. Petersburg
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Tyumen
Country [61] 0 0
Ukraine
State/province [61] 0 0
Chernivtsi
Country [62] 0 0
Ukraine
State/province [62] 0 0
Kiev
Country [63] 0 0
Ukraine
State/province [63] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index \[BMI\] greater than or equal to 30 kilogram per square meter \[kg/m\^2\]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment.

The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24.

Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development.
Trial website
https://clinicaltrials.gov/study/NCT00976937
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00976937