Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03798054 | Evaluation of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Patients With Type 2 Diabetes Insufficiently Controlled With Oral Antidiabetic Drug(s) | PHASE3 | COMPLETED | 878 | — | — | Feb 15, 2019 | Mar 1, 2021 | Jul 19, 2022 | 79 | China, Malaysia +2 |
| NCT02749890 | Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (LixiLan) to Lixisenatide on Top of Oral Anti-diabetic Drugs (OADs) With Type 2 Diabetes in Japan | PHASE3 | COMPLETED | 321 | — | — | May 9, 2016 | May 1, 2018 | Jun 16, 2020 | 61 | Japan |
| NCT01632163 | Assessment of the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Basal Insulin +/- Metformin | PHASE3 | COMPLETED | 447 | — | — | Oct 1, 2012 | May 1, 2015 | Jun 15, 2015 | 51 | China, India +2 |
| NCT01517412 | Comparison of Lixisenatide Injected Prior to the Main Meal of the Day Versus Prior to Breakfast in Type 2 Diabetic Patients on Metformin | PHASE3 | COMPLETED | 451 | — | — | Feb 1, 2012 | May 1, 2013 | Oct 14, 2016 | 82 | United States, Canada +8 |
| NCT01169779 | Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin | PHASE3 | COMPLETED | 391 | — | — | Jul 1, 2010 | Dec 1, 2011 | Oct 13, 2016 | 35 | China, Hong Kong +2 |
| NCT00975286 | 24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine | PHASE3 | COMPLETED | 446 | — | — | Oct 1, 2009 | Aug 1, 2011 | Oct 11, 2016 | 140 | United States, Argentina +24 |
| NCT00976937 | 24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years | PHASE3 | COMPLETED | 319 | — | — | Aug 1, 2009 | Mar 1, 2011 | Oct 11, 2016 | 92 | United States, Australia +11 |
| NCT01596504 | Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin | PHASE2 | COMPLETED | 142 | — | — | May 1, 2012 | Jul 1, 2013 | Oct 14, 2016 | 8 | Germany |
| NCT01175473 | Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes | PHASE2 | COMPLETED | 148 | — | — | Aug 1, 2010 | Nov 1, 2010 | Nov 28, 2016 | 7 | Germany |
| NCT02803918 | A Study on Safety, Pharmacokinetics and Pharmacodynamics of Lixisenatide in Pediatric Patients With Type 2 Diabetes Mellitus (T2DM) | PHASE1 | COMPLETED | 23 | — | — | May 17, 2017 | Jan 27, 2020 | Apr 25, 2022 | 11 | United States, Mauritius +4 |
| NCT01572649 | Evaluation of the Blood Levels of the Drug (Lixisenatide), the Plasma Glucose Levels and Safety in Paediatric and Adult Patients With Type 2 Diabetes | PHASE1 | COMPLETED | 24 | — | — | May 1, 2012 | Mar 1, 2014 | May 23, 2014 | 6 | United States, Mexico +2 |
Change in glycated hemoglobin (HbA1c) from baseline to Week 24
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.
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.
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. |
| Placebo | PLACEBO_COMPARATOR | 24-week treatment with placebo once daily on top of basal insulin with or without metformin (at least 1.0g/day) |
| 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 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 |
| 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 |
| Placebo | DRUG | Pharmaceutical form:solution Route of administration: subcutaneous injection |
| 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. |
| Liraglutide | DRUG | Pharmaceutical form:solution for injection Route of administration: subcutaneous |
| Pre-filled pen injector | DEVICE | - |
| Basal Insulin | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
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 (...