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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02058160




Registration number
NCT02058160
Ethics application status
Date submitted
6/02/2014
Date registered
7/02/2014
Date last updated
9/05/2017

Titles & IDs
Public title
Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes
Scientific title
A Randomized, 30-week, Active-controlled, Open Label, 2- Treatment Arm, Parallel-group, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine With or Without Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)
Secondary ID [1] 0 0
2013-003132-79
Secondary ID [2] 0 0
EFC12405
Universal Trial Number (UTN)
Trial acronym
LixiLan-L
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 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 - Insulin glargine/lixisenatide (HOE901/AVE0010)
Treatment: Drugs - Insulin glargine (HOE901)
Treatment: Drugs - Metformin (Background Drug)

Experimental: Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) - FRC once daily (QD) for 30 weeks. Dose individually adjusted.

Active comparator: Insulin glargine - Insulin glargine 100 U/mL QD for 30 weeks. Dose individually adjusted.


Treatment: Drugs: Insulin glargine/lixisenatide (HOE901/AVE0010)
Insulin glargine/lixisenatide FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using one of 2 SoloStar® pen-injectors: Pen A (ratio of 2 Units (U) of insulin glargine U 100:1 mcg of lixisenatide) or Pen B (ratio of 3 U of insulin glargine U 100:1 mcg of lixisenatide). After run-in, the FRC was initiated at a dose of either 20 U/10 mcg with Pen A or 30 U/10 mcg with Pen B, depending on participant's dose of Insulin glargine on the day prior to randomization.

Dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L). Pen A was used for administration of doses up to 40 U/20 mcg and Pen B for administration of doses from 30 U/10 mcg up to 60 U/20 mcg.

Treatment: Drugs: Insulin glargine (HOE901)
Insulin glargine was self-administered QD by SC injection at approximately the same time every day.

After screening, eligible participants entered 6 week run-in phase during which they were switched (if necessary) to insulin glargine and dose was stabilized. The first dose after randomization was same as the one administered on the day prior to randomization and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).

Treatment: Drugs: Metformin (Background Drug)
Pharmaceutical form: Tablet; Route of administration: Oral administration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30
Timepoint [1] 0 0
Baseline, Week 30
Secondary outcome [1] 0 0
Percentage of Participants With HbA1c <7.0% or =6.5% at Week 30
Timepoint [1] 0 0
Week 30
Secondary outcome [2] 0 0
Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30
Timepoint [2] 0 0
Baseline, Week 30
Secondary outcome [3] 0 0
Change in Body Weight From Baseline to Week 30
Timepoint [3] 0 0
Baseline, Week 30
Secondary outcome [4] 0 0
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30
Timepoint [4] 0 0
Baseline, Week 30
Secondary outcome [5] 0 0
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30
Timepoint [5] 0 0
Week 30
Secondary outcome [6] 0 0
Change in Daily Insulin Glargine Dose From Baseline to Week 30
Timepoint [6] 0 0
Baseline, Week 30
Secondary outcome [7] 0 0
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] = 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Timepoint [7] 0 0
Baseline up to Week 30
Secondary outcome [8] 0 0
Change in FPG From Baseline to Week 30
Timepoint [8] 0 0
Baseline, Week 30
Secondary outcome [9] 0 0
Change in 2-hour PPG From Baseline to Week 30
Timepoint [9] 0 0
Baseline, Week 30
Secondary outcome [10] 0 0
Percentage of Participants Reaching HbA1c <7.0% With No Documented Symptomatic Hypoglycemia (PG = 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
Timepoint [10] 0 0
Baseline up to Week 30
Secondary outcome [11] 0 0
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period
Timepoint [11] 0 0
Baseline up to Week 30
Secondary outcome [12] 0 0
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year
Timepoint [12] 0 0
First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Secondary outcome [13] 0 0
Percentage of Participants With Documented Symptomatic Hypoglycemia
Timepoint [13] 0 0
First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Secondary outcome [14] 0 0
Percentage of Participants With Severe Symptomatic Hypoglycemia
Timepoint [14] 0 0
First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])

Eligibility
Key inclusion criteria
Inclusion criteria :

* Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
* Treatment with basal insulin for at least 6 months before the screening visit.
* Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.
* Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.
* For participants receiving basal insulin and 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs could be 1 to 2 out of:

* metformin (more than or equal to 1500 mg/day or maximal tolerated dose),
* a sulfonylurea,
* a glinide,
* a dipeptidyl-peptidase-4 inhibitor,
* a sodium glucose co-transporter 2 inhibitor,
* Fasting Plasma Glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for participants receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for participants on basal insulin only or basal insulin plus metformin at screening visit.
* Signed written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Age under legal age of adulthood at screening visit.
* HbA1c at screening visit less than 7.5% or above 10%.
* Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
* Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.
* Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (=10 days) due to intercurrent illness is allowed.
* History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.
* Participant who had previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide FRC or had previously received lixisenatide.
* Use of weight loss drugs within 3 months prior to screening visit.
* Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
* Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.
* At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m^2.
* At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.
* At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.
* At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).
* Any contraindication to metformin use, according to local labeling, if the participant was taking metformin.
* Participant who had a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for participants, not treated with metformin.

Exclusion criteria for randomization:

* HbA1c less than 7% or above 10% .
* Mean fasting SMPG calculated from the self-measurements for 7 days the week before randomization visit was above 140 mg/dL (7.8 mmol/L).
* Average insulin glargine daily dose less than 20 Units or above 50 Units (in the week before randomization visit).
* Amylase and/or lipase more than 3 ULN .

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

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
Open (masking not used)
Who is / are masked / blinded?



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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036505 - Box Hill
Recruitment hospital [2] 0 0
Investigational Site Number 036501 - Heidelberg
Recruitment hospital [3] 0 0
Investigational Site Number 036504 - Parkville
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Delaware
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Florida
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Georgia
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Idaho
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Illinois
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Indiana
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Kentucky
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Maine
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Maryland
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Michigan
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Minnesota
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Montana
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Nebraska
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Nevada
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New Hampshire
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New Mexico
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New York
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North Carolina
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Texas
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Sabadell
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Valencia
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Sweden
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Ljungby
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Malmö
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Stockholm
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Ukraine
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Chernivtsi
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
State/province [134] 0 0
Vinnytsya

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Aroda VR, Rosenstock J, Wysham C, Unger J, Bellido... [More Details]