Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LIXISENATIDE · 26 trials · 5 indications
Change in glycated hemoglobin (HbA1c) from baseline to Week 24
Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine. Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
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 |
|---|---|---|
| Soliqua (insulin glargine/lixisenatide) | EXPERIMENTAL | iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning on top of metformin for 24 weeks. |
| Lantus (insulin glargine) | ACTIVE_COMPARATOR | Insulin glargine will be self-administered subcutaneously once daily at any time of the day on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period. |
| Lyxumia (lixisenatide) | ACTIVE_COMPARATOR | Lixisenatide will be self-administered subcutaneously once daily according to the locally approved label on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period. |
| LixiLan | EXPERIMENTAL | LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period. |
| lixisenatide | ACTIVE_COMPARATOR | Lixisenatide (AVE0010) is injected subcutaneously (under the skin) once daily. It will be initiated with Dose 1 for 1 week and then continue with Dose 2 for 1 week followed by the maintenance dose of Dose 3 up to the end of treatment period. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period. |
| Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) | EXPERIMENTAL | FRC once daily (QD) for 30 weeks. Dose individually adjusted. |
| Insulin Glargine | ACTIVE_COMPARATOR | Insulin glargine QD for 30 weeks. Dose individually adjusted. |
| 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 |
|---|---|---|
| Insulin glargine/Lixisenatide (HOE901/AVE0010) | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| Insulin glargine (HOE901) | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| Lixisenatide (AVE0010) | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| Metformin | DRUG | Pharmaceutical form: tablet Route of administration: oral |
| SGLT2 inhibitor | DRUG | Pharmaceutical form:tablet Route of administration: oral |
| Oral anti-diabetic drugs | DRUG | Pharmaceutical form: tablet Route of administration: Oral |
| Insulin glargine/lixisenatide Fixed Ratio Combination | DRUG | Insulin glargine/Lixisenatide FRC was self-administered by subcutaneous (SC) injection in the morning within one hour before breakfast using one of the 2 prefilled disposable SoloStar® pen-injectors: Pen A containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 50 mcg/mL lixisenatide in a ratio of 2 U:1 mcg, used for administration of doses from 10 U to 40 U (10 U/5mcg to 40 U/20mcg). Pen B containing 100 U/mL insulin glargine (Lantus, 100 U/mL) and 33 mcg/mL lixisenatide in a ratio of 3 U:1 mcg, used to administer doses from 41 U to 60 U (41 U/13 mcg to 60 U/20 mcg). The starting dose was 10 U/5 mcg. Dose was then adjusted individually 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) while avoiding hypoglycemia. |
| 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 | - |
| 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 : * Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1), treated for at least 3 months prior to the screening visit (V1) with metformin alone or metformin and a second oral antidiabetic treatment that can be a sulfonylurea (...
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LIXISENATIDE is an investigational small molecule being developed for Type 2 Diabetes Mellitus and Acute Coronary Syndrome. It is studied in patients with Type 2 Diabetes for glycemic control, including as monotherapy and in combination with metformin or basal insulin with or without sulfonylurea.
LIXISENATIDE is being developed by Sanofi, a company listed on the stock exchange under the ticker SNY. Sanofi is conducting clinical trials of LIXISENATIDE in multiple countries, including the United States, Japan, Germany, and South Korea.
LIXISENATIDE is in Phase 3 clinical development for Type 2 Diabetes Mellitus. It is an investigational drug and is not approved by the FDA. All 11 clinical trials for LIXISENATIDE have been completed, with no active trials currently ongoing.
LIXISENATIDE has been studied in completed clinical trials including NCT00763451, a Phase 3 trial in Type 2 Diabetes patients on top of metformin, and NCT00866658, a Phase 3 trial on top of basal insulin with or without sulfonylurea. NCT00905255 evaluated it as monotherapy in Japan.
LIXISENATIDE is a GLP-1 receptor agonist, as indicated by the trial titles. It works by activating the GLP-1 receptor, which helps regulate blood sugar levels in patients with Type 2 Diabetes Mellitus.
LIXISENATIDE is also known by the name LIXISENATIDE, with no alternative names provided. It is a distinct investigational compound developed by Sanofi for metabolic conditions such as Type 2 Diabetes Mellitus.