Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, 24-week, Open-label, 2-arm Parallel-group, Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine on Top of Metformin in Type 2 Diabetic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01476475
• Other study ID #: ACT12374
• Secondary ID: 2011-002090-36U1
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2011
• Last updated: January 27, 2014
• Start date: November 2011
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• The purpose of this study is to compare insulin glargine/ lixisenatide fixed ratio combination versus insulin glargine on glycemic control over 24 weeks, as evaluated by HbA1c (glycosylated hemoglobin) reduction in type 2 diabetic patients treated with metformin

Secondary Objectives:

• To compare insulin glargine/lixisenatide fixed ratio combination versus insulin glargine over 24 weeks on:

• Glycemic control in relation to a meal as evaluated by post-prandial plasma glucose and glucose excursions during a standardized meal test

• Percentage of patients reaching HbA1c <7% or ≤6.5%

• 7-point Self-Monitored Plasma Glucose (SMPG) profile

• Body weight

• Insulin glargine dose

• Fasting Plasma Glucose (FPG)

• Percentage of patients requiring rescue therapy during the 24-week open label treatment period

• To assess safety and tolerability of insulin glargine/ lixisenatide fixed ratio combination.

Description:

Approximately 27 weeks including a 24-week treatment period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Patient with type 2 diabetes mellitus diagnosed for at least 1 year.

• Metformin treatment at a stable dose of at least 1.5 g/day for at least 3 months prior to screening.

Exclusion criteria:

• Age < legal age of adulthood

• Screening HbA1c < 7% or > 10%

• Screening FPG > 250 mg/dL (> 13.9 mmol/L)

• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method

• Type 1 diabetes mellitus

• Treatment with glucose-lowering agent(s) other than metformin in a period of 3 months prior to screening

• Use of insulin within the last 6 months

• Previous use of insulin, except for episode(s) of short-term treatment (= 15 consecutive days) due to intercurrent illness

• Amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN) at screening

• Calcitonin = 20 pg/ml (5.9 pmol/l) at screening

• Alanine Transferase (ALT)> 3ULN at screening

• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy

• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g multiple endocrine neoplasia syndromes)

• Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure >180 mmHg or >110 mmHg, respectively

• Within the last 6 months prior to screening: history of heart failure requiring hospitalization, myocardial infarction, or stroke. Planned coronary, carotid or peripheral artery revascularisation procedures

• Body Mass Index (BMI) = 20 or > 40 kg/m²

• Any previous treatment with lixisenatide

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Insulin glargine /lixisenatide fixed ratio combination (HOE901/AVE0010)
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Insulin glargine (HOE901)
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Metformin
Route of administration: oral

Device:
• re-usable pen-type self-injector device

• disposable self injector device

Locations

Country	Name	City	State
Chile	Investigational Site Number 152401	Santiago
Chile	Investigational Site Number 152402	Santiago
Chile	Investigational Site Number 152403	Santiago
Chile	Investigational Site Number 152404	Santiago
Chile	Investigational Site Number 152405	Santiago
Czech Republic	Investigational Site Number 203403	Novy Jicin
Czech Republic	Investigational Site Number 203401	Plzen
Czech Republic	Investigational Site Number 203402	Praha 2
Czech Republic	Investigational Site Number 203405	Praha 8
Denmark	Investigational Site Number 208401	København Nv
Denmark	Investigational Site Number 208404	Køge
Denmark	Investigational Site Number 208402	Slagelse
Denmark	Investigational Site Number 208403	Svendborg
France	Investigational Site Number 250402	Narbonne
France	Investigational Site Number 250404	Poitiers Cedex
France	Investigational Site Number 250401	Vandoeuvre Les Nancy
Germany	Investigational Site Number 276401	Dresden
Germany	Investigational Site Number 276402	Ludwigshafen
Germany	Investigational Site Number 276403	Oberhausen
Hungary	Investigational Site Number 348401	Balatonfüred
Hungary	Investigational Site Number 348405	Budapest
Hungary	Investigational Site Number 348406	Budapest
Hungary	Investigational Site Number 348404	Debrecen
Hungary	Investigational Site Number 348402	Szeged
Hungary	Investigational Site Number 348403	Szeged
Lithuania	Investigational Site Number 440401	Kaunas
Lithuania	Investigational Site Number 440402	Kaunas
Lithuania	Investigational Site Number 440403	Kedainiai
Lithuania	Investigational Site Number 440404	Klaipeda
Mexico	Investigational Site Number 484404	Acapulco
Mexico	Investigational Site Number 484401	Cuernavaca
Mexico	Investigational Site Number 484405	Durango
Mexico	Investigational Site Number 484402	Guadalajara
Mexico	Investigational Site Number 484403	Guadalajara
Poland	Investigational Site Number 616405	Bialystok
Poland	Investigational Site Number 616406	Gdansk
Poland	Investigational Site Number 616403	Krakow
Poland	Investigational Site Number 616407	Lodz
Poland	Investigational Site Number 616404	Pulawy
Poland	Investigational Site Number 616402	Szczecin
Poland	Investigational Site Number 616401	Warszawa
Romania	Investigational Site Number 642402	Brasov
Romania	Investigational Site Number 642403	Bucuresti
Romania	Investigational Site Number 642405	Iasi
Romania	Investigational Site Number 642401	Oradea
Romania	Investigational Site Number 642406	Targu Mures
Romania	Investigational Site Number 642404	Timisoara
Slovakia	Investigational Site Number 703402	Bratislava
Slovakia	Investigational Site Number 703403	Kosice
Slovakia	Investigational Site Number 703406	Kosice
Slovakia	Investigational Site Number 703404	Moldava Nad Bodvou
Slovakia	Investigational Site Number 703405	Nitra
Slovakia	Investigational Site Number 703401	Zilina
Sweden	Investigational Site Number 752402	Skellefteå
Sweden	Investigational Site Number 752401	Stockholm
Sweden	Investigational Site Number 752403	Växjö
United States	Investigational Site Number 840410	Dallas	Texas
United States	Investigational Site Number 840413	Durham	Pennsylvania
United States	Investigational Site Number 840404	Hyattsville	Maryland
United States	Investigational Site Number 840401	Larenceville	Georgia
United States	Investigational Site Number 840411	Las Vegas	Nevada
United States	Investigational Site Number 840403	Lexington	Kentucky
United States	Investigational Site Number 840408	Little Rock	Arkansas
United States	Investigational Site Number 840407	Medford	Oregon
United States	Investigational Site Number 840402	Norman	Oklahoma
United States	Investigational Site Number 840412	Paramount	California
United States	Investigational Site Number 840414	Renton	Washington
United States	Investigational Site Number 840405	Rockville	Maryland
United States	Investigational Site Number 840417	Roswell	Georgia
United States	Investigational Site Number 840415	West Seneca	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Chile,  Czech Republic,  Denmark,  France,  Germany,  Hungary,  Lithuania,  Mexico,  Poland,  Romania,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c		from baseline to week 24	No
Secondary	Change in 2-hour post-prandial plasma glucose (PPG) during meal test		from baseline to week 24	No
Secondary	Change in 2-hour plasma glucose excursion during meal test	derived as: 2-hour post-prandial glucose - plasma glucose 30 minutes prior to the meal test, before IMP administration) from baseline to week 24	from baseline to week 24	No
Secondary	Percentage of patients reaching HbA1c =6.5 % or <7 %		at week 24	No
Secondary	Change in 7-point SMPG profiles		from baseline to week 24	No
Secondary	Change in body weight		from baseline to week 24	No
Secondary	Insulin glargine dose		at week 24	No
Secondary	Change in FPG		from baseline to week 24	No
Secondary	Percentage of patients requiring rescue therapy during the 24-week open-label treatment period		over the 24-week treatment period	No
Secondary	Change in 30-minute and 1-hour PPG and plasma glucose excursion during meal test		from baseline to week 24	No
Secondary	Percentage of patients reaching HbA1c <7% at week 24 with no documented symptomatic hypoglycemia during the 24-week open label treatment period		over the 24-week treatment period	No
Secondary	Percentage of patients reaching HbA1c <7% with no weight gain		at week 24	No