Efficacy and Safety of LixiLan Versus Insulin Glargine Alone Both With Metformin in Japanese With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs

ID: NCT02752412
Status: Recruiting
Phase: Phase 3
Start Date: May 17, 2016
First Submitted: April 20, 2016
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Japan
Conditions: Type 2 Diabetes Mellitus
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Study Description

Brief Summary

Primary Objective:

To compare LixiLan to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to week 26 in patients with type 2 diabetes mellitus.

Secondary Objective:

To compare overall efficacy and safety of LixiLan to insulin glargine over 26 weeks in patients with type 2 diabetes mellitus.

Detailed Description

The maximum study duration per patient will be approximately 41 weeks: an up to 14-week screening period (consisting of an up to 2-week screening phase and a 12-week run-in phase), a 26-week randomized treatment period, and a 3-day post-treatment safety follow-up period.
Condition or disease Intervention/treatment Phase

Type 2 Diabetes Mellitus

Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010)
Other Names
LixiLan
Drug: Insulin glargine U100 (HOE901)
Other Names
Lantus
Drug: Metformin
Other Names
Phase 3

Tracking Information

First Submitted DateApril 20, 2016
Last Update Posted DateFebruary 22, 2018
Start DateMay 17, 2016
Anticipated Completion DateOctober 03, 2018
Primary Completion DateOctober 03, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change from baseline in HbA1c [Time Frame: Baseline, 26 weeks]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Percentage of patients reaching HbA1c <7% or ≤6.5% [Time Frame: 26 weeks]

  • Change from baseline in 2-hour postprandial plasma glucose (PPG) during standardized meal test [Time Frame: Baseline, 26 weeks]

  • Change from baseline in blood glucose excursion during standardized meal test [Time Frame: Baseline, 26 weeks]

  • Change from baseline in 7-point self-monitoring plasma glucose (SMPG) profiles (each time point and average daily value) [Time Frame: Baseline, 26 weeks]

  • Change from baseline in body weight [Time Frame: Baseline, 26 weeks]

  • Change from baseline in FPG [Time Frame: Baseline, 26 weeks]

  • Change from baseline in daily dose of insulin glargine [Time Frame: Baseline, 26 weeks]

  • Percentage of patients reaching HbA1c <7% with no body weight gain [Time Frame: 26 weeks]

  • Percentage of patients reaching HbA1c <7% with no body weight gain and with no documented (PG ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia [Time Frame: 26 weeks]

  • Percentage of patients reaching HbA1c <7% with no documented (PG ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia [Time Frame: 26 weeks]

  • Percentage of patients requiring a rescue therapy [Time Frame: 26 weeks]

  • Number of hypoglycemic events [Time Frame: 26 weeks]

  • Number of adverse events [Time Frame: 26 weeks]

  • Measurement of anti-lixisenatide antibodies from baseline [Time Frame: Baseline, 26 weeks]

  • Measurement of anti-insulin antibodies from baseline [Time Frame: Baseline, 26 weeks]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety of LixiLan Versus Insulin Glargine Alone Both With Metformin in Japanese With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs
Official TitleA Randomized, Active-controlled, Open Label, 2-treatment Arm, and Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Combination to Insulin Glargine With Metformin in Japanese Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs
Brief Summary

Primary Objective:

To compare LixiLan to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to week 26 in patients with type 2 diabetes mellitus.

Secondary Objective:

To compare overall efficacy and safety of LixiLan to insulin glargine over 26 weeks in patients with type 2 diabetes mellitus.

Detailed Description

The maximum study duration per patient will be approximately 41 weeks: an up to 14-week screening period (consisting of an up to 2-week screening phase and a 12-week run-in phase), a 26-week randomized treatment period, and a 3-day post-treatment safety follow-up period.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
534
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Type 2 Diabetes Mellitus
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010)

Pharmaceutical form: solution Route of administration: subcutaneous

Other Names
LixiLan
Drug: Insulin glargine U100 (HOE901)

Pharmaceutical form: solution Route of administration: subcutaneous

Other Names
Lantus
Drug: Metformin

Pharmaceutical form: tablet Route of administration: oral

Other Names
Study Groups/Cohorts
LixiLan
LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Metformin will be continued.

insulin glargine
Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted. Metformin will be continued.

Study Arms
Active Comparator insulin glargine
Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted. Metformin will be continued.
Drug : Insulin glargine U100 (HOE901)
Pharmaceutical form: solution Route of administration: subcutaneous

Active Comparator insulin glargine
Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted. Metformin will be continued.
Drug : Metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental LixiLan
LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Metformin will be continued.
Drug : Metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental LixiLan
LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Metformin will be continued.
Drug : Insulin glargine/Lixisenatide (HOE901/AVE0010)
Pharmaceutical form: solution Route of administration: subcutaneous

Arm Intervention/Treatment
Active Comparator insulin glargine
Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted. Metformin will be continued.
Drug : Insulin glargine U100 (HOE901)
Active Comparator insulin glargine
Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted. Metformin will be continued.
Drug : Metformin
Experimental LixiLan
LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Metformin will be continued.
Drug : Metformin
Experimental LixiLan
LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Metformin will be continued.
Drug : Insulin glargine/Lixisenatide (HOE901/AVE0010)

Recruitment Information

Recruitment Status:Recruiting
Enrollment534
Completion DateOctober 03, 2018
Eligibility Criteria: Inclusion criteria :
- Patient with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1).
- Patient treated with a stable, once a day basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before the screening visit.
- The total daily basal insulin dose should be stable (± 20%) and <15 U/day for at least 1 month before the screening visit.
- Patient receiving 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 can be 1 to 2 out of:
- Metformin;
- Sulfonylurea (SU);
- Glinide;
- Dipeptidyl-peptidase-4 (DPP-4) inhibitor;
- Sodium glucose co-transporter 2 (SGLT2) inhibitor;
- Alpha glucosidase inhibitor (alpha-GI).
- Signed written informed consent.
Exclusion criteria:
- Age <20 years at screening visit.
- HbA1c at screening visit <7.5% or >9.5%.
- Fasting plasma glucose (FPG) >180 mg/dL (10.0 mmol/L) at screening visit.
- Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
- Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria in the 3 months before screening visit.
- Previous use of insulin regimen other than basal insulin, eg, prandial or pre-mixed insulin.
Note: Short-term treatment (≤10 days) due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator.
- Use of thiazolidinedione (TZD) within 6 months prior to screening visit.
- History of discontinuation of a previous treatment with a glucagon-like peptide-1(GLP-1) receptor agonist due to safety/ tolerability issues or lack of efficacy.
- Laboratory findings at the screening visit; including:
- Amylase and/or lipase >3 times the upper limit of the normal (ULN) laboratory range;
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN;
- Calcitonin ≥20 pg/mL (5.9 pmol/L);
- Positive serum pregnancy test.
- Any contraindication to metformin use according to local labeling.
- History of hypersensitivity to any GLP-1 receptor agonist or to metacresol.
- Contraindication to use of insulin glargine or lixisenatide according to local labeling. History of hypersensitivity to insulin glargine or to any of the excipients.
- Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).
- History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has now been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
- Exclusion criteria for randomization at the end of the run-in phase:
- HbA1c <7.5% or >9.5% at visit 6 (Week -1).
- Mean fasting self monitored plasma glucose (SMPG) >160 mg/dL (8.9 mmol/L), calculated from all available (minimum of 4 self-measurements) values during the 7 days prior to randomization.
Note:fasting SMPG on the day of randomization can be included if assessed before randomization.
- Average insulin glargine daily dose ≥15 U/day or <5U/day calculated for the last 3 days before Visit 7.
- Metformin total daily dose <750 mg/day.
- Amylase and/or lipase >3 ULN at Visit 6 (Week -1).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
GenderAll
Age20 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Japan

Administrative Information

NCT Number:NCT02752412
Other Study ID Numbers
EFC14113
U1111-1176-8378
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi