Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Lixisenatide (AVE0010)
Lixisenatide · 23 trials · 5 indications
Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed=participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID. Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
Change in HbA1C was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict the onset of primary CV endpoint over time. Number of observed participants with endpoint events were reported. A CV event adjudication committee (CAC) reviewed and adjudicated, in a blinded fashion, all potential events.
Percentage of patients who met both criteria (HbA1c \<7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Overview of adverse event profile is reported in terms of percentage of patients with treatment emergent adverse events (TEAEs) during the 24-week treatment period: any TEAE; any serious TEAE; any TEAE leading to death; and any TEAE leading to permanent treatment discontinuation.
Absolute change = HbA1c value at Week 12 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
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).
The area under the plasma glucose concentration time curve (GLU-AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours). GLU-AUC0:30-4:30h on Day -1 was the baseline. Change in GLU-AUC0:30-4:30h = GLU-AUC0:30-4:30h on Day 28 minus GLU-AUC0:30-4:30h on Day -1.
| Arm | Type | Description |
|---|---|---|
| Lixisenatide | EXPERIMENTAL | Lixisenatide 10 mcg once daily (QD) for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg. |
| Placebo | PLACEBO_COMPARATOR | Placebo (matched to lixisenatide) QD for 24 Weeks. |
| Insulin Glulisine QD | ACTIVE_COMPARATOR | Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin. |
| Insulin Glulisine TID | ACTIVE_COMPARATOR | Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin. |
| Lixisenatide Main Meal | EXPERIMENTAL | Lixisenatide 10 mcg once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24. |
| Lixisenatide Breakfast | ACTIVE_COMPARATOR | Lixisenatide 10 mcg QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24. |
| Sitagliptin | ACTIVE_COMPARATOR | 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. |
| Lixisenatide (Two-step Titration) | EXPERIMENTAL | 2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. |
| Lixisenatide (One-step Titration) | EXPERIMENTAL | 1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to end of treatment. |
| Placebo (Two-Step Titration) | PLACEBO_COMPARATOR | 2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. |
| Placebo (One-Step Titration) | PLACEBO_COMPARATOR | 1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment. |
| Lixisenatide (Morning Injection) | EXPERIMENTAL | 2-step initiation morning regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. |
| Lixisenatide (Evening Injection) | EXPERIMENTAL | 2-step initiation evening regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. |
| Placebo (Morning Injection) | PLACEBO_COMPARATOR | 2-step initiation morning regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. |
| Placebo (Evening Injection) | PLACEBO_COMPARATOR | 2-step initiation evening regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. |
| Exenatide | ACTIVE_COMPARATOR | 1-step initiation regimen of exenatide: 5 mcg twice daily (BID) for 4 weeks, followed by 10 mcg BID up to the end of treatment. |
| Lixisenatide 20 μg | EXPERIMENTAL | Subcutaneous 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. |
| Liraglutide 1.2 mg | ACTIVE_COMPARATOR | Subcutaneous 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. |
| Liraglutide 1.8 mg | ACTIVE_COMPARATOR | Subcutaneous 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. |
| Liraglutide | ACTIVE_COMPARATOR | 2-step initiation regimen of liraglutide: 0.6 milligram (mg) QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4. |
| Dose 1 | EXPERIMENTAL | 1 single administration of 5 µg lixisenatide (50 µL) once a day subcutaneously |
| Dose 2 | EXPERIMENTAL | 1 single administration of 10 µg lixisenatide (100 µL) once a day subcutaneously |
| Sequence 1: AVE0010/Placebo | EXPERIMENTAL | Period 1: lixisenatide 20 µg in 200 µL, one single dose Period 2: placebo 200 µL, one single dose |
| Sequence 2: Placebo/AVE0010 | EXPERIMENTAL | Period 1: placebo 200 µL, one single dose Period 2: lixisenatide 20 µg in 200 µL, one single dose |
| Name | Type | Description |
|---|---|---|
| Lixisenatide (AVE0010) | DRUG | Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection |
| Placebo | DRUG | Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection |
| Antidiabetic background therapy | DRUG | Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide \>10 mg, gliclazide \>160 mg), meglitinides (except repaglinide \>6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin. |
| Insulin glulisine QD | DRUG | Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before breakfast or dinner. The initial dose was 3-5 units and then individually titrated to obtain the SMPG value \>5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before lunch (if administered at breakfast) or at bedtime (if administered at dinner). |
| Insulin glulisine TID | DRUG | Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before each meal. The initial dose was 3-5 units for each meal and then individually titrated to obtain the SMPG value \>5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before the next meal or at bedtime (for injection at dinner). |
| Insulin Glargine (Mandatory background drug) | DRUG | Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL). |
| Metformin (Background drug) | DRUG | Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study. |
| Self-injector pen device (OptiClik®) | DEVICE | - |
| Metformin | DRUG | To be kept at stable dose (≥1.5 g/day) throughout the study. |
| Pen auto-injector | DEVICE | - |
| Sulfonylurea | DRUG | Sulfonylurea if given at screening, to be continued up to Week 24. In patients with a screening HbA1c \<8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values. In patients with a screening HbA1c \>=8%, the dose is not to be changed at randomization. In any case, after Week 12, sulfonylurea is to be continued at a stable dose. |
| Insulin glargine | DRUG | Dose to be adjusted to maintain a fasting SMPG between 100 and 80 mg/dL (5.6 and 4.4 mmol/L), inclusive. |
| Thiazolidinedione (TZD) | DRUG | TZD (either rosiglitazone or pioglitazone) if given, to be continued at stable dose up to Week 24. |
| Lixisenatide Placebo | DRUG | Self-administered by subcutaneous injections once daily within the hour preceding breakfast. |
| Sitagliptin | DRUG | Administered orally once a day in the morning with or without food at approximately the same time each day. |
| Sitagliptin Placebo | DRUG | Administered orally once a day in the morning with or without food at approximately the same time each day. |
| Basal Insulin | DRUG | To be continued at a stable dose. |
| Pioglitazone | DRUG | Dose to be kept stable. |
| Exenatide | DRUG | Self administered by subcutaneous injections twice daily within the hour preceding breakfast and within the hour preceding dinner. |
| Prefilled pen injector | DEVICE | - |
| Liraglutide | DRUG | Pharmaceutical form:solution for injection Route of administration: subcutaneous |
| Pre-filled pen injector | DEVICE | - |
Inclusion criteria : * Older participants, aged 70 years and above, with T2DM inadequately controlled on their current anti-diabetic pharmaceutical treatment regimen. * Signed written informed consent. Exclusion criteria: * At screening HbA1c ≤7.0% or \>10% (Acknowledging that the threshold of 7%...
Lixisenatide is a small molecule GLP1R agonist developed by Sanofi for type 2 diabetes and acute coronary syndrome. It is an investigational agent that has been studied in Phase 3 clinical trials, including 19 completed trials with a total enrollment of 6,796 participants. It is also known as AVE0010.
Lixisenatide is being studied for the treatment of type 2 diabetes and acute coronary syndrome. Clinical trials have evaluated it in adults with type 2 diabetes insufficiently controlled on basal insulin, in older patients aged 70 and above, and in comparison with insulin glulisine. It is not approved for these uses.
Lixisenatide targets GLP1R, the glucagon-like peptide-1 receptor, and acts as an agonist at this receptor. This target class is central to its investigational use in type 2 diabetes and cardiovascular conditions. The drug is a small molecule developed by Sanofi.
Lixisenatide is developed by Sanofi, which trades under the ticker SNY. Sanofi has sponsored the clinical development program, including Phase 3 trials in type 2 diabetes and a Phase 1 pediatric study. The drug is also identified by the code AVE0010.
Lixisenatide is in Phase 3 clinical development. All 19 recorded trials are completed, with no active trials currently listed, and total enrollment across the program is 6,796 participants. The trials include randomized, double-blind, placebo-controlled designs.
Lixisenatide has been studied in completed trials including NCT02803918, a Phase 1 pediatric study in type 2 diabetes; NCT01798706, a Phase 3 trial in patients aged 70 and older; NCT01768559, a Phase 3 comparison with insulin glulisine; and NCT01632163, a Phase 3 trial in patients with type 2 diabetes insufficiently controlled on basal insulin.
Yes, lixisenatide is also known as AVE0010. The names refer to the same Sanofi compound, a GLP1R agonist small molecule studied in type 2 diabetes and acute coronary syndrome. Searches for AVE0010 or lixisenatide refer to the same investigational drug.