24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine

Type 2 Diabetes Mellitus Clinical Trial

— GetGoal Duo1  

Official title:

A Randomized, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Double-blind Treatment Period Assessing the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine and Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00975286
• Other study ID #: EFC10781
• Secondary ID: EudraCT : 2008-0
• Status: Completed
• Phase: Phase 3
• First received: September 10, 2009
• Last updated: April 9, 2014
• Start date: October 2009
• Est. completion date: August 2011

Study information

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

Clinical Trial Summary

The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidinediones (TZDs), over a period of 24 weeks of treatment.

The primary objective is to assess the effects of lixisenatide in comparison to placebo, when added to insulin glargine and metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effects of lixisenatide on the percentage of patients reaching HbA1c less than (<) 7 percent (%) and less than or equal to (<=) 6.5%, plasma glucose (fasting, postprandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses, to evaluate safety and tolerability (including anti-lixisenatide antibody assessment), and to assess the impact on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated.

Description:

The study comprises 3 periods:

• An up to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on top of metformin +/-TZDs.

• At the end of the run-in phase, patients whose HbA1c (centralized assay) is greater than or equal to (>=) 7% and less than or equal to (<=) 9% and whose mean fasting self-monitored plasma glucose (SMPG) calculated from the self measurements for the 7 days prior to Visit 12 (Week -1) is <=140 milligram per deciliter (mg/dL) (7.8 millimole per liter [mmol/L]), would enter a 24-week double-blind randomized treatment period comparing lixisenatide to placebo (on top of insulin glargine + metformin +/- TZDs).

• A 3-day safety follow up period.

Maximum duration is of 39 weeks +/- 7 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 446
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with insulin glargine and metformin

Exclusion criteria:

• HbA1c <7% or greater than (>)10% at screening

• At the time of screening age < legal age of majority

• Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method

• Type 1 diabetes mellitus

• Metformin not at a stable dose of at least 1.5 gram per day for at least 3 months prior to the screening visit

• Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea (SU) and TZDs (for example, alpha glucosidase inhibitor, other glucagon like peptide-1 [GLP-1] receptor agonists, dipeptidyl peptidase-IV [DPP-IV] inhibitors, insulin etc.) within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit

• History of hypoglycemia unawareness

• Body Mass Index (BMI) less than or equal to (<=) 20 kilogram per square meter (kg/m^2)

• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes)

• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening

• Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion within 3 months prior to the time of screening

• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization

• Known history of drug or alcohol abuse within 6 months prior to the time of screening

• Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram or vital signs at the time of screening that in the judgment of the Investigator or any sub investigator precludes safe completion of the study or constrains efficacy assessment such as active malignant tumor or other major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period

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

• Laboratory findings at the time of screening: amylase and/or lipase, alanine aminotransferase >3 times upper limit of the normal (ULN) laboratory range; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody, positive serum pregnancy test in females of childbearing potential; and calcitonin >=20 picogram per milliliter (pg/mL) (5.9 picomole per milliliter [pmol/L])

• Patients who are considered by the Investigator or any sub investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as scheduled visits, being able to do self-injections, likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol, patient being investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol etc.)

• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening

• Use of any investigational drug within 3 months prior to screening

• Renal impairment defined with serum creatinine > 1.4 mg/dL in women and > 1.5 mg/dL in men

• History of hypersensitivity to insulin glargine or to any of the excipients

• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening

• Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)

• Allergic reaction to any GLP-1 receptor agonist in the past (for example, exenatide, liraglutide) or to metacresol

• Additional exclusion criteria during or at the end of the run-in phase before randomization: informed consent withdrawal (patient who was not willing to continue or failed to return), mean fasting SMPG calculated from the self-measurements for the 7 days prior to Visit 12 (Week -1) was >140 mg/dL (7.8 mmol/L) and HbA1c measured at Visit 12 (Week -1) is <7% or >9%, amylase and/or lipase > 3 times the ULN at Visit 12 (Week -1), patients with fasting plasma glucose (FPG) above the threshold value described for rescue (that is, FPG >240 mg/dL [13.3 mmol/L]), patients with any adverse event, which, by the judgment of the Investigator precludes the inclusion in the double-blind randomized treatment phase, and lack of compliance to protocol or to insulin glargine treatment during the run-in phase

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Lixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
• Placebo
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
• Insulin glargine
Dose to be adjusted to maintain a fasting SMPG between 100 and 80 mg/dL (5.6 and 4.4 mmol/L), inclusive.

Device:
• Pen auto-injector
Lantus® SoloStar® OptiClik®

Drug:
• Metformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.
• Thiazolidinedione (TZD)
TZD (either rosiglitazone or pioglitazone) if given, to be continued at stable dose up to Week 24.

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Investigational Site Number 032204	Buenos Aires
Argentina	Sanofi-Aventis Investigational Site Number 032201	Capital Federal
Argentina	Sanofi-Aventis Investigational Site Number 032205	Capital Federal
Argentina	Sanofi-Aventis Investigational Site Number 032209	Capital Federal
Argentina	Sanofi-Aventis Investigational Site Number 032211	Corrientes
Argentina	Sanofi-Aventis Investigational Site Number 032202	Parana
Argentina	Sanofi-Aventis Investigational Site Number 032203	Rosario
Brazil	Sanofi-Aventis Investigational Site Number 076207	Belem
Brazil	Sanofi-Aventis Investigational Site Number 076202	Brasilia
Brazil	Sanofi-Aventis Investigational Site Number 076205	Porto Alegre
Brazil	Sanofi-Aventis Investigational Site Number 076204	Sao Paulo
Canada	Sanofi-Aventis Investigational Site Number 124219	Brampton
Canada	Sanofi-Aventis Investigational Site Number 124213	Chatham
Canada	Sanofi-Aventis Investigational Site Number 124208	Chilliwack
Canada	Sanofi-Aventis Investigational Site Number 124215	Etobicoke
Canada	Sanofi-Aventis Investigational Site Number 124205	Quebec
Canada	Sanofi-Aventis Investigational Site Number 124202	Red Deer
Canada	Sanofi-Aventis Investigational Site Number 124218	Thornhill
Canada	Sanofi-Aventis Investigational Site Number 124201	Toronto
Canada	Sanofi-Aventis Investigational Site Number 124207	Toronto
Canada	Sanofi-Aventis Investigational Site Number 124209	Victoria
Canada	Sanofi-Aventis Investigational Site Number 124217	Winnipeg
Chile	Sanofi-Aventis Investigational Site Number 152201	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152202	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152203	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152204	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152205	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152206	Santiago
Colombia	Sanofi-Aventis Investigational Site Number 170204	Barranquilla
Colombia	Sanofi-Aventis Investigational Site Number 170201	Bogota
Colombia	Sanofi-Aventis Investigational Site Number 170202	Bogota
Czech Republic	Sanofi-Aventis Investigational Site Number 203202	Hradec Kralove
Czech Republic	Sanofi-Aventis Investigational Site Number 203204	Praha 5
Denmark	Sanofi-Aventis Investigational Site Number 208202	Frederiksberg
Denmark	Sanofi-Aventis Investigational Site Number 208201	København Nv
Denmark	Sanofi-Aventis Investigational Site Number 208205	Slagelse
Estonia	Sanofi-Aventis Investigational Site Number 233201	Pärnu
Estonia	Sanofi-Aventis Investigational Site Number 233203	Tallinn
Estonia	Sanofi-Aventis Investigational Site Number 233204	Tartu
Estonia	Sanofi-Aventis Investigational Site Number 233202	Viljandimaa
France	Sanofi-Aventis Investigational Site Number 250204	Amiens Cedex 1
France	Sanofi-Aventis Investigational Site Number 250206	La Rochelle Cedex
France	Sanofi-Aventis Investigational Site Number 250203	Le Creusot
France	Sanofi-Aventis Investigational Site Number 250201	Nantes
France	Sanofi-Aventis Investigational Site Number 250202	Pierre Benite
Germany	Sanofi-Aventis Investigational Site Number 276201	Dresden
Germany	Sanofi-Aventis Investigational Site Number 276202	Mainz
Germany	Sanofi-Aventis Investigational Site Number 276204	St. Ingbert-Oberwürzbach
Hungary	Sanofi-Aventis Investigational Site Number 348205	Balatonfüred
Hungary	Sanofi-Aventis Investigational Site Number 348202	Budapest
Hungary	Sanofi-Aventis Investigational Site Number 348207	Budapest
Hungary	Sanofi-Aventis Investigational Site Number 348204	Debrecen
Hungary	Sanofi-Aventis Investigational Site Number 348206	Gyula
Hungary	Sanofi-Aventis Investigational Site Number 348203	Szeged
Hungary	Sanofi-Aventis Investigational Site Number 348201	Zalaegerszeg
India	Sanofi-Aventis Investigational Site Number 356210	Ahmedabad
India	Sanofi-Aventis Investigational Site Number 356202	Bangalore
India	Sanofi-Aventis Investigational Site Number 356204	Bangalore
India	Sanofi-Aventis Investigational Site Number 356206	Bangalore
India	Sanofi-Aventis Investigational Site Number 356201	Belgaum
India	Sanofi-Aventis Investigational Site Number 356205	Chennai
India	Sanofi-Aventis Investigational Site Number 356208	Indore
India	Sanofi-Aventis Investigational Site Number 356203	Karnal
India	Sanofi-Aventis Investigational Site Number 356207	Kochi
India	Sanofi-Aventis Investigational Site Number 356209	Nagpur
Israel	Sanofi-Aventis Investigational Site Number 376202	Haifa
Israel	Sanofi-Aventis Investigational Site Number 376201	Holon
Israel	Sanofi-Aventis Investigational Site Number 376204	Kfar Saba
Israel	Sanofi-Aventis Investigational Site Number 376203	Tel Hashomer
Italy	Sanofi-Aventis Investigational Site Number 380201	Milano
Italy	Sanofi-Aventis Investigational Site Number 380202	Perugia
Malaysia	Sanofi-Aventis Investigational Site Number 458203	Kelantan
Malaysia	Sanofi-Aventis Investigational Site Number 458202	Kuala Lumpur
Mexico	Sanofi-Aventis Investigational Site Number 484201	Cuernavaca
Mexico	Sanofi-Aventis Investigational Site Number 484204	Durango
Mexico	Sanofi-Aventis Investigational Site Number 484203	Guadalajara
Mexico	Sanofi-Aventis Investigational Site Number 484206	México City
Mexico	Sanofi-Aventis Investigational Site Number 484205	Tlalnepantla
Netherlands	Sanofi-Aventis Investigational Site Number 528203	Amsterdam
Netherlands	Sanofi-Aventis Investigational Site Number 528202	Groningen
Netherlands	Sanofi-Aventis Investigational Site Number 528204	Zwijndrecht
Poland	Sanofi-Aventis Investigational Site Number 616202	Krakow
Poland	Sanofi-Aventis Investigational Site Number 616208	Lubin
Poland	Sanofi-Aventis Investigational Site Number 616206	Plock
Poland	Sanofi-Aventis Investigational Site Number 616207	Pulawy
Poland	Sanofi-Aventis Investigational Site Number 616205	Sopot
Poland	Sanofi-Aventis Investigational Site Number 616201	Szczecin
Poland	Sanofi-Aventis Investigational Site Number 616203	Zabrze
Puerto Rico	Sanofi-Aventis Investigational Site Number 840226	Ponce
Puerto Rico	Sanofi-Aventis Investigational Site Number 840216	San Juan
Romania	Sanofi-Aventis Investigational Site Number 642204	Brasov
Romania	Sanofi-Aventis Investigational Site Number 642208	Bucharest
Romania	Sanofi-Aventis Investigational Site Number 642205	Deva
Romania	Sanofi-Aventis Investigational Site Number 642203	Iasi
Romania	Sanofi-Aventis Investigational Site Number 642202	Oradea
Romania	Sanofi-Aventis Investigational Site Number 642206	Targu Mures
Romania	Sanofi-Aventis Investigational Site Number 642201	Timisoara
Romania	Sanofi-Aventis Investigational Site Number 642207	Timisoara
Russian Federation	Sanofi-Aventis Investigational Site Number 643203	Saratov
Russian Federation	Sanofi-Aventis Investigational Site Number 643202	St. Petersburg
South Africa	Sanofi-Aventis Investigational Site Number 710202	Cape Town
South Africa	Sanofi-Aventis Investigational Site Number 710201	Durban
South Africa	Sanofi-Aventis Investigational Site Number 710203	Pretoria
Sweden	Sanofi-Aventis Investigational Site Number 752204	Göteborg
Sweden	Sanofi-Aventis Investigational Site Number 752203	Härnösand
Sweden	Sanofi-Aventis Investigational Site Number 752205	Luleå
Sweden	Sanofi-Aventis Investigational Site Number 752202	Malmö
Sweden	Sanofi-Aventis Investigational Site Number 752201	Stockholm
Taiwan	Sanofi-Aventis Investigational Site Number 158204	Changhua
Taiwan	Sanofi-Aventis Investigational Site Number 158203	Taichung
Taiwan	Sanofi-Aventis Investigational Site Number 158201	Taichung R.O.C.
Taiwan	Sanofi-Aventis Investigational Site Number 158202	Tainan Hsien
Ukraine	Sanofi-Aventis Investigational Site Number 804203	Chernivtsi
Ukraine	Sanofi-Aventis Investigational Site Number 804201	Kiev
Ukraine	Sanofi-Aventis Investigational Site Number 804202	Kyiv
Ukraine	Sanofi-Aventis Investigational Site Number 804205	Kyiv
Ukraine	Sanofi-Aventis Investigational Site Number 804204	Vinnytsya
United States	Sanofi-Aventis Investigational Site Number 840211	Baton Rouge	Louisiana
United States	Sanofi-Aventis Investigational Site Number 840219	Brighton	Michigan
United States	Sanofi-Aventis Investigational Site Number 840229	Bristol	Tennessee
United States	Sanofi-Aventis Investigational Site Number 840215	Concord	California
United States	Sanofi-Aventis Investigational Site Number 840210	Dallas	Texas
United States	Sanofi-Aventis Investigational Site Number 840208	Fargo	North Dakota
United States	Sanofi-Aventis Investigational Site Number 840205	Germantown	Tennessee
United States	Sanofi-Aventis Investigational Site Number 840214	Greenbrae	California
United States	Sanofi-Aventis Investigational Site Number 840206	Hot Springs	Arkansas
United States	Sanofi-Aventis Investigational Site Number 840217	Houston	Texas
United States	Sanofi-Aventis Investigational Site Number 840228	Houston	Texas
United States	Sanofi-Aventis Investigational Site Number 840230	Hyattsville	Maryland
United States	Sanofi-Aventis Investigational Site Number 840201	Little Rock	Arkansas
United States	Sanofi-Aventis Investigational Site Number 840225	Mentor	Ohio
United States	Sanofi-Aventis Investigational Site Number 840223	Mesa	Arizona
United States	Sanofi-Aventis Investigational Site Number 840212	Mountain Home	Arkansas
United States	Sanofi-Aventis Investigational Site Number 840227	Norfolk	Virginia
United States	Sanofi-Aventis Investigational Site Number 840221	Orlando	Florida
United States	Sanofi-Aventis Investigational Site Number 840202	Philadelphia	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840213	Plano	Texas
United States	Sanofi-Aventis Investigational Site Number 840222	Portland	Oregon
United States	Sanofi-Aventis Investigational Site Number 840209	Rockville	Maryland
United States	Sanofi-Aventis Investigational Site Number 840231	Sea Girt	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  Colombia,  Czech Republic,  Denmark,  Estonia,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Malaysia,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Romania,  Russian Federation,  South Africa,  Sweden,  Taiwan,  Ukraine, 

References & Publications (1)

Riddle MC, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Silvestre L, Ping L, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, rando — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24	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.	Baseline, Week 24	No
Other	Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia	Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.	First dose of study drug up to 3 days after the last dose administration	Yes
Primary	Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	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 14 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.	Baseline, Week 24	No
Secondary	Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24	The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 24	No
Secondary	Change From Baseline in Glucose Excursion at Week 24	Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 24	No
Secondary	Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24	Patients recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime once in a week and the average value for the 7-time points was calculated. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 24	No
Secondary	Change From Baseline in Body Weight at Week 24	Change was calculated by subtracting baseline value from Week 24 value. 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.	Baseline, Week 24	No
Secondary	Change From Baseline in Average Insulin Glargine Daily Dose at Week 24	Change was calculated by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 24	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Change was calculated by subtracting baseline value from Wee 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day 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.	Baseline, Week 24	No
Secondary	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24	The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 14 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.	Week 24	No
Secondary	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24	The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 14 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.	Week 24	No
Secondary	Percentage of Patients Requiring Rescue Therapy During the Double-blind Period	Routine fasting SMPG, central laboratory FPG and HbA1c values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG and HbA1c were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >200 milligram/deciliter (mg/dL) (11.1 mmol/L) or HbA1c >9%, from Week 8 to Week 24: fasting SMPG/FPG >180 mg/dL (10.0 mmol/L) or HbA1c >8.5%. 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.	Baseline up to Week 24	No
Secondary	Change From Baseline in Treatment Satisfaction Score (Sum of Items 1, 4, 5, 6, 7 and 8 of DTSQ) at Week 24	Change was calculated by subtracting baseline value from Week 24 value. DTSQ: 8-item questionnaire to assess treatment satisfaction and patient perception of hyper and hypoglycemia. Each question (Q) scored on a Likert scale from 0 to 6. Six items (Q1 and 4-8; higher score = more satisfaction) measured treatment satisfaction and were summed to calculate treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied). Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively and lower scores represented good perceived blood glucose control. 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.	Baseline, Week 24	No