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

Diabetes Mellitus, Type 2 Clinical Trial

— BRIGHT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02738151
• Other study ID #: LPS14584
• Secondary ID: 2015-005101-36U1
• Status: Completed
• Phase: Phase 4
• Start date: May 19, 2016
• Est. completion date: August 15, 2017

Study information

• Verified date: August 2018
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 929
• Est. completion date: August 15, 2017
• Est. primary completion date: August 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin glargine, 300U/mL
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L).
• Insulin degludec, 100 U/mL
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L). Route of administration: subcutaneous
• Non-insulin anti-diabetic treatment
Background therapy: Oral Anti diabetics Drugs (OADs), Glucagon-like peptide-1 (GLP-1) receptor agonist.

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 100001	Sofia
Bulgaria	Investigational Site Number 100002	Sofia
Bulgaria	Investigational Site Number 100003	Sofia
Croatia	Investigational Site Number 191001	Rijeka
Croatia	Investigational Site Number 191002	Rijeka
Croatia	Investigational Site Number 191003	Zagreb
Czechia	Investigational Site Number 203009	Hlucin
Czechia	Investigational Site Number 203006	Jilove u Prahy
Czechia	Investigational Site Number 203005	Liberec
Czechia	Investigational Site Number 203001	Pardubice
Czechia	Investigational Site Number 203007	Praha 1
Czechia	Investigational Site Number 203008	Praha 2
Czechia	Investigational Site Number 203002	Praha 8
Czechia	Investigational Site Number 203004	Vsetin
Denmark	Investigational Site Number 208003	Aarhus
Denmark	Investigational Site Number 208002	Hillerød
Denmark	Investigational Site Number 208001	København NV.
Denmark	Investigational Site Number 208004	Odense
France	Investigational Site Number 250002	La Roche Sur Yon
France	Investigational Site Number 250003	La Rochelle Cedex 1
France	Investigational Site Number 250001	Nantes cedex 01
France	Investigational Site Number 250006	Nimes
France	Investigational Site Number 250005	POITIERS Cedex
France	Investigational Site Number 250007	Venissieux
Greece	Investigational Site Number 300005	Alexandroupolis
Greece	Investigational Site Number 300001	Athens
Greece	Investigational Site Number 300002	Athens
Greece	Investigational Site Number 300003	Athens
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348004	Budapest
Hungary	Investigational Site Number 348003	Gyöngyös
Israel	Investigational Site Number 376001	Haifa
Israel	Investigational Site Number 376004	Haifa
Israel	Investigational Site Number 376008	Haifa
Israel	Investigational Site Number 376009	Kfar Saba
Israel	Investigational Site Number 376002	Petach tikva
Israel	Investigational Site Number 376006	Tel Aviv
Israel	Investigational Site Number 376003	Tel Hashomer
Israel	Investigational Site Number 376007	Tel-Aviv
Italy	Investigational Site Number 380007	Bari
Italy	Investigational Site Number 380009	Catanzaro
Italy	Investigational Site Number 380010	Chieti
Italy	Investigational Site Number 380014	Milano
Italy	Investigational Site Number 380002	Moncalieri
Italy	Investigational Site Number 380011	Napoli
Italy	Investigational Site Number 380008	Roma
Italy	Investigational Site Number 380015	Roma
Italy	Investigational Site Number 380016	Roma
Italy	Investigational Site Number 380013	Sesto San Giovanni
Italy	Investigational Site Number 380005	Torino
Italy	Investigational Site Number 380012	Verona
Romania	Investigational Site Number 642007	Brasov
Romania	Investigational Site Number 642008	Brasov
Romania	Investigational Site Number 642001	Bucharest
Romania	Investigational Site Number 642013	Bucharest
Romania	Investigational Site Number 642015	Bucuresti
Romania	Investigational Site Number 642003	Cluj-Napoca
Romania	Investigational Site Number 642009	Constanta
Romania	Investigational Site Number 642014	Iasi
Romania	Investigational Site Number 642005	Oradea
Romania	Investigational Site Number 642012	Oradea
Romania	Investigational Site Number 642004	Targu-Mures
Romania	Investigational Site Number 642006	Targu-Mures
Romania	Investigational Site Number 642010	Targu-Mures
Serbia	Investigational Site Number 688001	Belgrade
Serbia	Investigational Site Number 688002	Nis
Serbia	Investigational Site Number 688003	Nis
Slovakia	Investigational Site Number 703006	Kosice
Slovakia	Investigational Site Number 703002	Lubochna
Slovakia	Investigational Site Number 703001	Moldava nad Bodvou
Slovakia	Investigational Site Number 703003	Sabinov
Slovakia	Investigational Site Number 703005	Trebisov
Sweden	Investigational Site Number 752102	Lund
Sweden	Investigational Site Number 752101	Skövde
Switzerland	Investigational Site Number 756003	Olten
Switzerland	Investigational Site Number 756001	St. Gallen
United Kingdom	Investigational Site Number 826001	Chertsey
United Kingdom	Investigational Site Number 826005	Gillingham
United Kingdom	Investigational Site Number 826008	Lincoln
United Kingdom	Investigational Site Number 826002	London
United Kingdom	Investigational Site Number 826009	Manchester
United Kingdom	Investigational Site Number 826006	Margate
United Kingdom	Investigational Site Number 826004	Swansea
United States	Investigational Site Number 840051	Anaheim	California
United States	Investigational Site Number 840093	Anderson	South Carolina
United States	Investigational Site Number 840036	Arlington Heights	Illinois
United States	Investigational Site Number 840005	Avon	Indiana
United States	Investigational Site Number 840029	Beaver	Pennsylvania
United States	Investigational Site Number 840075	Bradenton	Florida
United States	Investigational Site Number 840079	Bristol	Tennessee
United States	Investigational Site Number 840006	Chattanooga	Tennessee
United States	Investigational Site Number 840048	Chesterfield	Missouri
United States	Investigational Site Number 840010	Chicago	Illinois
United States	Investigational Site Number 840081	Chino	California
United States	Investigational Site Number 840063	Council Bluffs	Iowa
United States	Investigational Site Number 840007	Dallas	Texas
United States	Investigational Site Number 840086	Dallas	Texas
United States	Investigational Site Number 840098	Des Moines	Iowa
United States	Investigational Site Number 840101	Des Moines	Iowa
United States	Investigational Site Number 840056	Downingtown	Pennsylvania
United States	Investigational Site Number 840041	Flint	Michigan
United States	Investigational Site Number 840057	Flint	Michigan
United States	Investigational Site Number 840097	Greenville	South Carolina
United States	Investigational Site Number 840070	Greer	South Carolina
United States	Investigational Site Number 840060	Hickory	North Carolina
United States	Investigational Site Number 840004	Houston	Texas
United States	Investigational Site Number 840027	Houston	Texas
United States	Investigational Site Number 840040	Houston	Texas
United States	Investigational Site Number 840046	Houston	Texas
United States	Investigational Site Number 840016	Huntington Park	California
United States	Investigational Site Number 840054	Hurst	Texas
United States	Investigational Site Number 840011	Hyattsville	Maryland
United States	Investigational Site Number 840088	Knoxville	Tennessee
United States	Investigational Site Number 840002	La Jolla	California
United States	Investigational Site Number 840023	Las Vegas	Nevada
United States	Investigational Site Number 840045	Las Vegas	Nevada
United States	Investigational Site Number 840071	Lawrenceville	Georgia
United States	Investigational Site Number 840031	Linden	New Jersey
United States	Investigational Site Number 840091	Los Angeles	California
United States	Investigational Site Number 840017	Mesquite	Texas
United States	Investigational Site Number 840008	Missouri City	Texas
United States	Investigational Site Number 840064	Morganton	North Carolina
United States	Investigational Site Number 840076	New Port Richey	Florida
United States	Investigational Site Number 840077	New Tazewell	Tennessee
United States	Investigational Site Number 840024	Norfolk	Virginia
United States	Investigational Site Number 840044	North Myrtle Beach	South Carolina
United States	Investigational Site Number 840058	Northridge	California
United States	Investigational Site Number 840026	Ocoee	Florida
United States	Investigational Site Number 840095	Ogden	Utah
United States	Investigational Site Number 840022	Oklahoma City	Oklahoma
United States	Investigational Site Number 840025	Oklahoma City	Oklahoma
United States	Investigational Site Number 840084	Olive Branch	Mississippi
United States	Investigational Site Number 840052	Palm Harbor	Florida
United States	Investigational Site Number 840080	Palm Harbor	Florida
United States	Investigational Site Number 840021	Palm Springs	California
United States	Investigational Site Number 840061	Paris	Kentucky
United States	Investigational Site Number 840066	Phoenix	Arizona
United States	Investigational Site Number 840018	Port Charlotte	Florida
United States	Investigational Site Number 840012	Renton	Washington
United States	Investigational Site Number 840020	Richmond	Virginia
United States	Investigational Site Number 840001	Rockville	Maryland
United States	Investigational Site Number 840085	Roswell	Georgia
United States	Investigational Site Number 840032	Salt Lake City	Utah
United States	Investigational Site Number 840094	San Antonio	Texas
United States	Investigational Site Number 840087	Santa Ana	California
United States	Investigational Site Number 840038	Sheffield	Alabama
United States	Investigational Site Number 840069	Simpsonville	South Carolina
United States	Investigational Site Number 840072	Statesboro	Georgia
United States	Investigational Site Number 840039	Stockbridge	Georgia
United States	Investigational Site Number 840009	Sugar Land	Texas
United States	Investigational Site Number 840030	Torrance	California
United States	Investigational Site Number 840033	Troy	Michigan
United States	Investigational Site Number 840065	Van Nuys	California
United States	Investigational Site Number 840053	Waco	Texas
United States	Investigational Site Number 840096	West Des Moines	Iowa
United States	Investigational Site Number 840043	Wilmington	North Carolina
United States	Investigational Site Number 840082	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Czechia,  Denmark,  France,  Greece,  Hungary,  Israel,  Italy,  Romania,  Serbia,  Slovakia,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24	The DTSQs is a validated questionnaire to assess participant's satisfaction with their diabetes treatment. It consists of 8 items that are answered on a Likert scale from 0 to 6. Total treatment satisfaction score is the sum of items 1, 4-8 scores and ranged from 0 (no satisfaction) to 36 (high satisfaction with treatment). Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.	Baseline, Week 12 and Week 24
Primary	Change From Baseline in HbA1c to Week 24	Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Adjusted Least Square (LS) means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 24-week on-treatment period.	Baseline, Week 24
Secondary	Change From Baseline in HbA1c to Week 12	Change in HbA1c was calculated by subtracting baseline value from Week 12 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.	Baseline, Week 12
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24	Change in FPG was calculated by subtracting baseline value from Week 12 and Week 24 value. Adjusted LS means were obtained from MMRM including post baseline values during the 24-week on-treatment period.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24	Fasting SMPG was measured by the participant before breakfast and before the administration of the glucose-lowering agents once a day during the study. Adjusted LS means were obtained from MMRM including post baseline values during the 24 week on treatment period.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point	8-point SMPG profiles were measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point	4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24	The 8-point SMPG profile was measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Adjusted LS means were obtained from MMRM.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24	Adjusted LS means were obtained from MMRM. Variability was assessed by the mean of coefficient of variation calculated over at least 3 SMPG measured during the 7 days preceding the given visit.	Baseline, Week 12 and Week 24
Secondary	Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24	Adjusted LS means were obtained from MMRM.	Baseline, Week 12 and Week 24
Secondary	Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24	Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.	Week 12, and Week 24
Secondary	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	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed by plasma glucose =<3.9 mmol/L (=<70 mg/dL).	Week 12, and Week 24
Secondary	Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period	Percentage of participants With Sulphonylurea or Meglitinide dose reduction/ discontinuation due to Hypoglycemia during 24 Week treatment period were reported. Only participants with Sulphonylurea or meglitinides at Screening as per actual strata were taken into account in this analysis.	Baseline to Week 24
Secondary	Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period	Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. Threshold values at Week 12: FPG >200 mg/dL (11 mmol/L), or HbA1c >8.5%.	Baseline to Week 24
Secondary	Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24	Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis.	Baseline, Week 12 and Week 24
Secondary	Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Assessment was done by treatment period (for =<12 weeks, for >12 weeks to =<24 weeks (24W)). Percentage of participants with at least one hypoglycemia (hypo) event at any time of the day were reported.	Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Secondary	Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycaemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time). Assessment was done by treatment period (for =<12 weeks, for >12 weeks to =<24 weeks).	Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Secondary	Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L).	Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Secondary	Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time).	Day 1-Week 12, Week 13-Week 24, and 24 Week Period