Comparison of SAR342434 to Humalog as the Rapid Acting In... | NCT02273180

ID	Type	Description	Link
2013-002945-12	EudraCT Number
U1111-1131-5038	Other Identifier	UTN

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
SAR342434	Experimental	SAR342434 before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.	Drug: SAR342434 Drug: Insulin glargine HOE901
Humalog	Active Comparator	Humalog before meals intake on top of QD Insulin Glargine, up to Week 52.	Drug: Humalog Drug: Insulin glargine HOE901

Interventions

Name	Type	Description	Arm Group Labels	Other Names
SAR342434	Drug	SAR342434 100 U/mL (dose range of 1 Unit to 80 Units) self-administered by deep subcutaneous (SC) injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour post prandial plasma glucose (PPG) in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c From Baseline to Week 26	Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square 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 main 6-month period and adequate contrasts at Week 26.	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With HbA1c <7.0% at Week 26	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.	Week 26
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

Other Outcomes

Measure	Description	Time Frame
Change in Daily Insulin Dose From Baseline to Week 26 and Week 52	Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 and Week 52 values respectively.	Baseline, Week 26, Week 52

Eligibility Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840049		Tucson	Arizona	85714	United States
Investigational Site Number 840016

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28722480	Background	Garg SK, Wernicke-Panten K, Rojeski M, Pierre S, Kirchhein Y, Jedynasty K. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 1 Diabetes Also Using Insulin Glargine-SORELLA 1 Study. Diabetes Technol Ther. 2017 Sep;19(9):516-526. doi: 10.1089/dia.2017.0117. Epub 2017 Aug 30.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	SAR342434	SAR342434 100 Units(U)/mL subcutaneous (SC) injection, before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
FG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-0.42± 0.051 OG001-0.47± 0.05

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was performed using a MMRM approach with treatment groups, randomization strata, visits and treatment-by-visit interaction as fixed categorical effects, and baseline HbA1c value and baseline HbA1c value-by-visit interaction as continuous fixed covariates. An unstructured correlation matrix was used to model within-participant errors.					Least Square (LS) Mean Difference	0.06	Standard Error of the Mean	0.071	2-Sided	95	-0.084	0.197			SAR342434 vs. Humalog		Non-Inferiority

Secondary

Percentage of Participants With HbA1c <7.0% at Week 26

Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.

Analysis was performed on ITT population.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Units	Counts
Participants	OG000

Secondary

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the main 6-month period and adequate contrasts at Week 26.

Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline FPG assessment during the main 6-month period.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Units	Counts
Participants	OG000

Secondary

Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26

Mean 24-hour plasma glucose concentration was calculated based on 7-point self-measured plasma glucose (SMPG) profiles with plasma glucose measurements before and 2-hours after each main meal and at bedtime. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the main 6-month period and adequate contrasts at Week 26.

Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline mean 24-hour plasma glucose concentration assessment during the main 6-month period.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Secondary

Change in Post Prandial Plasma Glucose (PPG) Excursion From Baseline to Week 26

Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour PPG minus plasma glucose value obtained 30 minutes prior to start of the meal. Values of plasma glucose excursions at each visit were then calculated as average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the main 6-month period and adequate contrasts at Week 26.

Analysis was performed on ITT population. Here, number analyzed in each row = participants with at least one post-baseline data during the main 6-month period for specified categories.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Secondary

Number of Hypoglycemia Events (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia) Per Participant-Year

Number of treatment-emergent hypoglycemia events per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (<3.0 mmol/L) were also analyzed.

Analysis was performed on safety population that included all participants randomized and exposed to at least 1 dose of investigational medicinal product (IMP) (SAR342434 or Humalog), regardless of the amount of treatment administered.

Posted

Number

events per participant-year

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Secondary

Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions

Percentage of participants with hypersensitivity reactions and injection site reactions were reported.

Analysis was performed on safety population.

Posted

Number

percentage of participants

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Treatment Emergent Anti-insulin Antibodies (AIAs)

Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were those who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample). Participants with treatment-boosted AIAs were those with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period, in those participants with pre-existing AIA).

Analysis was performed on anti-insulin antibody population that included all participants randomized and exposed to at least 1 dose of IMP (SAR342434 or Humalog) with at least one AIA sample available for analysis during the 12-month on-treatment period.

Posted

Number

percentage of participants

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Other Pre-specified

Change in Daily Insulin Dose From Baseline to Week 26 and Week 52

Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 and Week 52 values respectively.

Analysis was performed on safety population. Here, number analyzed in each row = participants with available data for specified categories.

Posted

Mean

Standard Deviation

U/kg

Baseline, Week 26, Week 52

ID	Title	Description
OG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
OG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	1	252	20	252	46	252
EG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	0	254	19	254	41	254

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Enterocolitis haemorrhagic	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Cardiac death	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0011 affected254 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0003 affected252 at risk EG0012 affected254 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0012 affected254 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Wrong drug administered	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0012 affected254 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected252 at risk EG0013 affected254 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Cerebral infarction	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Cerebral ventricle dilatation	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Hypoglycaemic coma	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected252 at risk EG0016 affected254 at risk
Migraine	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected252 at risk EG0010 affected254 at risk
Abortion threatened	Pregnancy, puerperium and perinatal conditions	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Pregnancy of partner	Social circumstances	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk
Gastrectomy	Surgical and medical procedures	MedDRA 19.0	Systematic Assessment	EG0000 affected252 at risk EG0011 affected254 at risk

Non-inferiority of SAR342434 over Humalog was demonstrated if upper bound of 2-sided 95% confidence interval(CI) of difference between SAR342434 & Humalog was <0.3%.Inverse non-inferiority of Humalog over SAR342434 was tested using hierarchical step-down testing procedure:if non-inferiority of SAR342434 over Humalog was demonstrated,then inverse non-inferiority of Humalog over SAR342434 was tested, demonstrated if lower bound of 2-sided 95%CI of difference between SAR342434 & Humalog was >-0.3%.

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D061266	Insulin, Short-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D049528	Insulin, Long-Acting

ID	Title	Description
BG000	SAR342434	SAR342434 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
BG001	Humalog	Humalog 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
BG002	Total	Total of all reporting groups

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment		EG00033 affected252 at risk EG00128 affected254 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment		EG00015 affected252 at risk EG00114 affected254 at risk

ID	Term
C000623163	SAR342434
D061268	Insulin Lispro
D000069036	Insulin Glargine