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Type 2 Diabetes MellitusPhase 2NCT01596504

Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

A Phase 2 study testing Lixisenatide (AVE0010), Liraglutide and Insulin Glargine in people with Type 2 Diabetes Mellitus, run by Sanofi at 8 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Primary Objective: To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Lixisenatide (AVE0010), Liraglutide and Insulin Glargine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
8 sitesGermany
Study dates
May 2012to Jul 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants with T2DM diagnosed at least 1 year before the screening visit.
  • Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3 months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior to screening) alone or combined with a stable dose of metformin with or without dipeptidyl peptidase 4 (DPP-4) inhibitor or sulfonylurea.
  • Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%.
  • Body mass index (BMI) between 20 and 40 kg/m^2.

Who cannot join

  • Pregnant women or breastfeeding women.
  • Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal reflux disease requiring medical treatment within 6 months prior to the time of screening.
  • Any previous treatment with lixisenatide or participation in a previous study with lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety concern or lack of efficacy.
  • Allergic reaction to any glucagon-like peptide-1 (GLP-1) agonist in the past (eg, exenatide) or to metacresol.
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease.
  • Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC.
  • The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites
  • Investigational Site Number 276008

    Berlin, 10117

  • Investigational Site Number 276006

    Berlin, 14050

  • Investigational Site Number 276004

    Kiel, 24105

  • Investigational Site Number 276002

    Mainz, 55116

  • Investigational Site Number 276005

    Mönchengladbach, 41061

  • Investigational Site Number 276007

    München, 80636

  • Investigational Site Number 276003

    Neu-Ulm, 89231

  • Investigational Site Number 276001

    Neuss, 41460

Other trials in Germany

About this study

Official title: An Open-label, Randomized, Three-parallel-group Study on Pharmacodynamic Effects of 8-week QD Treatment With Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

Primary Objective:

  • To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at the end of a 8-week treatment period in participants with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).
Read more

Secondary Objectives:

  • To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after an 8-week treatment period in participants with T2DM not adequately controlled with insulin glargine (± metformin) on:
  • Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast,
  • Appetite perceptions after standardized dinner,
  • Gastric emptying after a standardized labelled test meal,
  • Fasting plasma glucose, 24-hour plasma glucose profile,
  • Glycosylated hemoglobin (HbA1c),
  • Insulin glargine dose,
  • 7-point self monitored plasma glucose (SMPG),
  • Body weight and waist circumference,
  • 24-hour heart rate and blood pressure,
  • To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin).
Read the detailed description

Up to 2-week screening period

  • A run-in period of 12 weeks at maximum including a forced titration with insulin glargine up to 11 weeks and 1 baseline pharmacodynamic assessment week
  • A 8-week treatment(s) period(s) up to Day 57
  • Follow-up: 7 ±2 days after the last treatment day
  • Total study duration approximately 14 weeks up to 23 weeks
Being tested
Lixisenatide (AVE0010), Liraglutide, Insulin Glargine, Metformin
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lixisenatide (AVE0010)Drug

    Pharmaceutical form: solution for injection self-administered with a pen-like injector (OptiClik®).

    Route of administration: subcutaneous

  • LiraglutideDrug

    Also called Victoza®

    Pharmaceutical form:solution for injection

    Route of administration: subcutaneous

  • Insulin GlargineDrug

    Also called Lantus® SoloSTAR®

    Doses to be adjusted to maintain a fasting self-measured plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL)

  • MetforminDrug

    If previously taken metformin to be continued at stable dose throughout the study

Study groups in NCT01596504
Study groupRoleWhat they receive
Lixisenatide 20 μgExperimentalSubcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
Receives: Drug: Lixisenatide (AVE0010); Drug: Insulin Glargine; Drug: Metformin
Liraglutide 1.2 mgActive comparatorSubcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin.
Receives: Drug: Liraglutide; Drug: Insulin Glargine; Drug: Metformin
Liraglutide 1.8 mgActive comparatorSubcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.
Receives: Drug: Liraglutide; Drug: Insulin Glargine; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours

    Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration [time: 0.5 hours]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

    Measured: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56

Secondary outcomes (16)
  1. Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours

    Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration [time: 0.5 hours]) to 5 hours after breakfast start (time: 5.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

    Measured: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

  2. Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56

    Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. The 2-hour PPG test measured blood glucose 2 hours after start of a standardised breakfast.

    Measured: Day 56

  3. Change From Baseline to Day 56 in PPG Excursion

    Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. PPG excursion was determined on Day -3 (Baseline) and Day 56 as the maximum change in PPG from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

    Measured: 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

  4. Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG)

    Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. The value of FPG on Day -3 was the baseline.

    Measured: 0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56

  5. Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG)

    Seven-point SMPG (before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime) was measured using Freestyle Precision glucometer and average of the 7 measurements was calculated.

    Measured: Before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime on Day -3 (Baseline) and on Day 56

  6. Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours

    C-peptide was assessed using the Electro Chemiluminescence Immuno Assay.The range of the method was 0.2 to 25 nanogram per millilitre (ng/mL) and the LOD was 0.07 ng/mL. Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in C-peptide from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

    Measured: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

  7. Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours

    Glucagon was assessed using the radioimmunoassay. The range of the method was 4.7 to 150 picomole per litre (pmol/L). Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in glucagon from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

    Measured: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

  8. Change From Baseline to Day 56 in HbA1c

    HbA1C was assessed using the high performance liquid chromatography method.

    Measured: Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56

  9. Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose

    Measured: Day -7 (Baseline), Day 56

  10. Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2)

    Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry.

    Measured: 0 (prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55

  11. Change From Baseline to Day 55 in Gastric Emptying Coefficient

    Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry. Gastric emptying coefficient was derived from a mathematical formula that describes the gastric emptying rate and gives an overall index of gastric emptying.

    Measured: 0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55

  12. Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate

    The baseline value was the 24-hour mean on Day -2/-1 determined as overall, night and daytime mean. Measurements were made every 15 minutes from 07:00 to 23:00 (daytime) and every 30 minutes from 23:00 to 07:00 (night-time) at baseline and Day 57/58. Measurements were obtained after 10 minutes in the supine resting position.

    Measured: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/-1 (Baseline) and Day 57/58

  13. Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure

    The baseline value was the 24-hour means on Day -2/-1 determined as overall, night and day-time mean. Measurements were made every 15 minutes from 07:00 to 23:00 (day-time) and every 30 minutes from 23:00 to 07:00 (night-time) at baseline and at Day 57/58. Measurements were obtained after 10 minutes in the supine resting position.

    Measured: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/ -1 (Baseline) and Day 57/58

  14. Change From Baseline to Day 57 in Body Weight

    Measured: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57

  15. Change From Baseline to Day 57 in Waist Circumference

    Measured: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57

  16. Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast

    Visual Analogue Scale, 100 mm in length with words anchored at each end, expressing the most positive (100 mm) and the most negative rating (0 mm), was used to assess hunger, satiety, fullness and prospective food consumption. Responses were measured as distance from the left end of the line to the mark. Mean change from baseline was calculated for each parameter separately.

    Measured: 0.5 (8:00 clock time, prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours on Day -3; 0 (prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2012 (estimated)
  2. Study startMay 2012
  3. Primary completionJul 2013
  4. Study completionJul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01596504
Sponsor's protocol ID
PDY12625
Other IDs
2012-000027-40, U1111-1124-1364
Status last verified
Aug 2016
First submitted
7 May 2012
Last updated
14 Oct 2016
Data monitoring committee
No

Publications

  • Meier JJ, Rosenstock J, Hincelin-Mery A, Roy-Duval C, Delfolie A, Coester HV, Menge BA, Forst T, Kapitza C. Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial. Diabetes Care. 2015 Jul;38(7):1263-73. doi: 10.2337/dc14-1984. Epub 2015 Apr 17.

    PubMed 25887358

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lixisenatide (AVE0010), Liraglutide and Insulin Glargine in people with Type 2 Diabetes Mellitus, run by Sanofi at 8 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours (time frame: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01596504, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2016.

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