Clinical trial NCT02738151: Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist
Official title: A 24-week, Multicenter, Randomized, Open-Label, Parallel-group StudyComparing the Efficacy and Safety of Toujeo® and Tresiba® in Insulin-NaivePatients With Type 2 Diabetes Mellitus Not Adequately Controlled With OralAntihyperglycemic Drug(s) ± GLP-1 Receptor Agonist
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 929
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change from Baseline to Week 24.

Secondary Objectives:

Change From Baseline in HbA1c to Week 12

To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® at week 12 and week 24 on:

* Change in Fasting plasma glucose (FPG);
* Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5%;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5% without severe and/or confirmed hypoglycemia
* Frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.

To assess the safety in each treatment group.

To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).

Percentage of participants requiring rescue therapy.

Detailed description: The maximum study duration per participant was approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period (including 12 weeks active titration), and a 7-day posttreatment safety follow-up period.

Eligibility criteria: Inclusion criteria :

* Adult participants with type 2 diabetes mellitus (T2DM) inadequately controlled with OADs therapy with/without GLP-1 receptor agonist at stable dose for at least 3 months.
* Signed written informed consent.

Exclusion criteria:

* Age \<18 years.
* HbA1c \<7.5% or \>10.5% (at screening visit). Body mass index (BMI) \<25 kg/m\^2 or \>40 kg/m\^2.
* History of T2DM for less than 1 year before screening.
* Less than 6 months before screening on OADs treatment and GLP-1 receptor agonist (if taken).
* Current or previous insulin use except for a maximum of 8 consecutive days or totally 15 days (eg, acute illness, surgery) during the last year prior to screening.
* Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit.
* Participant receiving only noninsulin antihyperglycemic drugs not approved for combination with insulin according to local labelling/local treatment guideline.
* History of hypoglycemia unawareness or repeated episodes of severe hypoglycemia or metabolic acidosis, including hospitalization for diabetic ketoacidosis during the last 12 months prior to screening.
* Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period.
* End stage renal disease.
* Any acute or chronic condition that in the opinion of Investigator would affect the safety of participant, compliance, or study results.
* Any contraindication to use of Toujeo® or Tresiba® as defined in the national product label, hypersensitivity to Toujeo® or Tresiba® active ingredients or one of the excipients.
* Pregnant or breast-feeding women.

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

Primary outcomes:
measure: Change From Baseline in HbA1c to Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in HbA1c to Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24
timeFrame: Week 12, and Week 24
measure: Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event
timeFrame: Week 12, and Week 24
measure: Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period
timeFrame: Baseline to Week 24
measure: Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period
timeFrame: Baseline to Week 24
measure: Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period
timeFrame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
measure: Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period
timeFrame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
measure: Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period
timeFrame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
measure: Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period
timeFrame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Other outcomes:
measure: Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24
timeFrame: Baseline, Week 12 and Week 24
Locations:
city: Sheffield
country: United States
facility: Investigational Site Number 840038
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 840066
state: Arizona
city: Anaheim
country: United States
facility: Investigational Site Number 840051
state: California
city: Chino
country: United States
facility: Investigational Site Number 840081
state: California
city: Huntington Park
country: United States
facility: Investigational Site Number 840016
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 840002
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840091
state: California
city: Northridge
country: United States
facility: Investigational Site Number 840058
state: California
city: Palm Springs
country: United States
facility: Investigational Site Number 840021
state: California
city: Santa Ana
country: United States
facility: Investigational Site Number 840087
state: California
city: Torrance
country: United States
facility: Investigational Site Number 840030
state: California
city: Van Nuys
country: United States
facility: Investigational Site Number 840065
state: California
city: Bradenton
country: United States
facility: Investigational Site Number 840075
state: Florida
city: New Port Richey
country: United States
facility: Investigational Site Number 840076
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 840026
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840052
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840080
state: Florida
city: Port Charlotte
country: United States
facility: Investigational Site Number 840018
state: Florida
city: Lawrenceville
country: United States
facility: Investigational Site Number 840071
state: Georgia
city: Roswell
country: United States
facility: Investigational Site Number 840085
state: Georgia
city: Statesboro
country: United States
facility: Investigational Site Number 840072
state: Georgia
city: Stockbridge
country: United States
facility: Investigational Site Number 840039
state: Georgia
city: Arlington Heights
country: United States
facility: Investigational Site Number 840036
state: Illinois
city: Chicago
country: United States
facility: Investigational Site Number 840010
state: Illinois
city: Avon
country: United States
facility: Investigational Site Number 840005
state: Indiana
city: Council Bluffs
country: United States
facility: Investigational Site Number 840063
state: Iowa
city: Des Moines
country: United States
facility: Investigational Site Number 840098
state: Iowa
city: Des Moines
country: United States
facility: Investigational Site Number 840101
state: Iowa
city: West Des Moines
country: United States
facility: Investigational Site Number 840096
state: Iowa
city: Paris
country: United States
facility: Investigational Site Number 840061
state: Kentucky
city: Hyattsville
country: United States
facility: Investigational Site Number 840011
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840001
state: Maryland
city: Flint
country: United States
facility: Investigational Site Number 840041
state: Michigan
city: Flint
country: United States
facility: Investigational Site Number 840057
state: Michigan
city: Troy
country: United States
facility: Investigational Site Number 840033
state: Michigan
city: Olive Branch
country: United States
facility: Investigational Site Number 840084
state: Mississippi
city: Chesterfield
country: United States
facility: Investigational Site Number 840048
state: Missouri
city: Las Vegas
country: United States
facility: Investigational Site Number 840023
state: Nevada
city: Las Vegas
country: United States
facility: Investigational Site Number 840045
state: Nevada
city: Linden
country: United States
facility: Investigational Site Number 840031
state: New Jersey
city: Hickory
country: United States
facility: Investigational Site Number 840060
state: North Carolina
city: Morganton
country: United States
facility: Investigational Site Number 840064
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 840043
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 840082
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigational Site Number 840025
state: Oklahoma
city: Oklahoma City
country: United States
facility: Investigational Site Number 840022
state: Oklahoma
city: Beaver
country: United States
facility: Investigational Site Number 840029
state: Pennsylvania
city: Downingtown
country: United States
facility: Investigational Site Number 840056
state: Pennsylvania
city: Anderson
country: United States
facility: Investigational Site Number 840093
state: South Carolina
city: Greenville
country: United States
facility: Investigational Site Number 840097
state: South Carolina
city: Greer
country: United States
facility: Investigational Site Number 840070
state: South Carolina
city: North Myrtle Beach
country: United States
facility: Investigational Site Number 840044
state: South Carolina
city: Simpsonville
country: United States
facility: Investigational Site Number 840069
state: South Carolina
city: Bristol
country: United States
facility: Investigational Site Number 840079
state: Tennessee
city: Chattanooga
country: United States
facility: Investigational Site Number 840006
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 840088
state: Tennessee
city: New Tazewell
country: United States
facility: Investigational Site Number 840077
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 840007
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840086
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840027
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840004
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840040
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840046
state: Texas
city: Hurst
country: United States
facility: Investigational Site Number 840054
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 840017
state: Texas
city: Missouri City
country: United States
facility: Investigational Site Number 840008
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840094
state: Texas
city: Sugar Land
country: United States
facility: Investigational Site Number 840009
state: Texas
city: Waco
country: United States
facility: Investigational Site Number 840053
state: Texas
city: Ogden
country: United States
facility: Investigational Site Number 840095
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 840032
state: Utah
city: Norfolk
country: United States
facility: Investigational Site Number 840024
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840020
state: Virginia
city: Renton
country: United States
facility: Investigational Site Number 840012
state: Washington
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100001
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100002
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100003
city: Rijeka
country: Croatia
facility: Investigational Site Number 191001
city: Rijeka
country: Croatia
facility: Investigational Site Number 191002
city: Zagreb
country: Croatia
facility: Investigational Site Number 191003
city: Hlucin
country: Czechia
facility: Investigational Site Number 203009
city: Jilove u Prahy
country: Czechia
facility: Investigational Site Number 203006
city: Liberec
country: Czechia
facility: Investigational Site Number 203005
city: Pardubice
country: Czechia
facility: Investigational Site Number 203001
city: Praha 1
country: Czechia
facility: Investigational Site Number 203007
city: Praha 2
country: Czechia
facility: Investigational Site Number 203008
city: Praha 8
country: Czechia
facility: Investigational Site Number 203002
city: Vsetin
country: Czechia
facility: Investigational Site Number 203004
city: Aarhus
country: Denmark
facility: Investigational Site Number 208003
city: Hillerød
country: Denmark
facility: Investigational Site Number 208002
city: København NV.
country: Denmark
facility: Investigational Site Number 208001
city: Odense
country: Denmark
facility: Investigational Site Number 208004
city: La Roche Sur Yon
country: France
facility: Investigational Site Number 250002
city: La Rochelle Cedex 1
country: France
facility: Investigational Site Number 250003
city: Nantes cedex 01
country: France
facility: Investigational Site Number 250001
city: Nimes
country: France
facility: Investigational Site Number 250006
city: POITIERS Cedex
country: France
facility: Investigational Site Number 250005
city: Venissieux
country: France
facility: Investigational Site Number 250007
city: Alexandroupolis
country: Greece
facility: Investigational Site Number 300005
city: Athens
country: Greece
facility: Investigational Site Number 300001
city: Athens
country: Greece
facility: Investigational Site Number 300002
city: Athens
country: Greece
facility: Investigational Site Number 300003
city: Budapest
country: Hungary
facility: Investigational Site Number 348004
city: Budapest
country: Hungary
facility: Investigational Site Number 348002
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Gyöngyös
country: Hungary
facility: Investigational Site Number 348003
city: Haifa
country: Israel
facility: Investigational Site Number 376001
city: Haifa
country: Israel
facility: Investigational Site Number 376004
city: Haifa
country: Israel
facility: Investigational Site Number 376008
city: Kfar Saba
country: Israel
facility: Investigational Site Number 376009
city: Petach tikva
country: Israel
facility: Investigational Site Number 376002
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376006
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376003
city: Tel-Aviv
country: Israel
facility: Investigational Site Number 376007
city: Bari
country: Italy
facility: Investigational Site Number 380007
city: Catanzaro
country: Italy
facility: Investigational Site Number 380009
city: Chieti
country: Italy
facility: Investigational Site Number 380010
city: Milano
country: Italy
facility: Investigational Site Number 380014
city: Moncalieri
country: Italy
facility: Investigational Site Number 380002
city: Napoli
country: Italy
facility: Investigational Site Number 380011
city: Roma
country: Italy
facility: Investigational Site Number 380008
city: Roma
country: Italy
facility: Investigational Site Number 380015
city: Roma
country: Italy
facility: Investigational Site Number 380016
city: Sesto San Giovanni
country: Italy
facility: Investigational Site Number 380013
city: Torino
country: Italy
facility: Investigational Site Number 380005
city: Verona
country: Italy
facility: Investigational Site Number 380012
city: Brasov
country: Romania
facility: Investigational Site Number 642007
city: Brasov
country: Romania
facility: Investigational Site Number 642008
city: Bucharest
country: Romania
facility: Investigational Site Number 642001
city: Bucharest
country: Romania
facility: Investigational Site Number 642013
city: Bucuresti
country: Romania
facility: Investigational Site Number 642015
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642003
city: Constanta
country: Romania
facility: Investigational Site Number 642009
city: Iasi
country: Romania
facility: Investigational Site Number 642014
city: Oradea
country: Romania
facility: Investigational Site Number 642005
city: Oradea
country: Romania
facility: Investigational Site Number 642012
city: Targu-Mures
country: Romania
facility: Investigational Site Number 642010
city: Targu-Mures
country: Romania
facility: Investigational Site Number 642004
city: Targu-Mures
country: Romania
facility: Investigational Site Number 642006
city: Belgrade
country: Serbia
facility: Investigational Site Number 688001
city: Nis
country: Serbia
facility: Investigational Site Number 688002
city: Nis
country: Serbia
facility: Investigational Site Number 688003
city: Kosice
country: Slovakia
facility: Investigational Site Number 703006
city: Lubochna
country: Slovakia
facility: Investigational Site Number 703002
city: Moldava nad Bodvou
country: Slovakia
facility: Investigational Site Number 703001
city: Sabinov
country: Slovakia
facility: Investigational Site Number 703003
city: Trebisov
country: Slovakia
facility: Investigational Site Number 703005
city: Lund
country: Sweden
facility: Investigational Site Number 752102
city: Skövde
country: Sweden
facility: Investigational Site Number 752101
city: Olten
country: Switzerland
facility: Investigational Site Number 756003
city: St. Gallen
country: Switzerland
facility: Investigational Site Number 756001
city: Chertsey
country: United Kingdom
facility: Investigational Site Number 826001
city: Gillingham
country: United Kingdom
facility: Investigational Site Number 826005
city: Lincoln
country: United Kingdom
facility: Investigational Site Number 826008
city: London
country: United Kingdom
facility: Investigational Site Number 826002
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826009
city: Margate
country: United Kingdom
facility: Investigational Site Number 826006
city: Swansea
country: United Kingdom
facility: Investigational Site Number 826004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Cheng A, Ritzel R, Bosnyak Z, Devisme C, Cali AMG, Sieber J, Stella P, Wang X, Frias JP, Roussel R, Bolli GB. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care. 2018 Oct;41(10):2147-2154. doi: 10.2337/dc18-0559. Epub 2018 Aug 13.