A Study in China Evaluating the Safety and Efficacy of Ad... | NCT01590797

NCT01590797

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions 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
Sitagliptin	Experimental	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Drug: Sitagliptin Biological: Insulin Drug: Metformin
Placebo	Placebo Comparator	Participants treated with placebo matching sitagliptin, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Drug: Placebo Biological: Insulin Drug: Metformin

Name	Type	Description	Arm Group Labels	Other Names
Sitagliptin	Drug	Sitagliptin 100 mg once daily for 24 weeks	Sitagliptin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin		Baseline and Week 24
Number of Participants With One or More Adverse Events	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to Week 26
Number of Participants Discontinuing Study Medication Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin		Baseline and Week 24
Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

has T2DM
is currently on a stable regimen of pre-mixed, intermediate-acting, or long-acting insulin at a dose of at least 12 U/day, either alone or in combination with metformin >=1500 mg/day for ≥ 10 weeks
has a Visit 1/Screening HbA1C between 7.5% and 11.0%
is a male, or a female who is highly unlikely to conceive during the study and for 14 days after the last dose of study medication

Exclusion Criteria:

has been treated with any antihyperglycemic therapies other than a protocol-required insulin (alone or with metformin) within the prior 12 weeks or has ever

been treated with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 mimetic or analogue

is currently on treatment with daily use (one or more injections per day) of

pre-prandial short-acting or rapid-acting insulin

has a history of 2 or more episodes of hypoglycemia resulting in seizure,

coma, or loss of consciousness, or has had recurrent episodes of hypoglycemia over the past 8 weeks

has a history of intolerance or hypersensitivity, or has any contraindication to sitagliptin, insulin, or metformin
is on a weight loss program and not in the maintenance phase, or has started a weight loss medication or has undergone bariatric surgery within 12 months
has undergone a surgical procedure within 4 weeks or has planned major surgery during the study
has a medical history of active liver disease
has had new or worsening signs or symptoms of coronary heart disease within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder
has a diagnosis of congestive heart failure with New York Heart Association Class III - IV cardiac status
has a systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 90 mmHg
has human immunodeficiency virus (HIV)
has severe peripheral vascular disease
is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
has a history of malignancy ≤ 5 years before the study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
has a clinically important hematological disorder (such as aplastic anemia,

myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

is pregnant or breast feeding, or is expecting to conceive or donate eggs during the study, including 14 days after the last dose of study medication
is a user of recreational or illicit drugs or has had a recent history of drug abuse

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27740719	Result	Shankar RR, Bao Y, Han P, Hu J, Ma J, Peng Y, Wu F, Xu L, Engel SS, Jia W. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2 diabetes. J Diabetes Investig. 2017 May;8(3):321-329. doi: 10.1111/jdi.12585. Epub 2016 Dec 9.

ID	Type	URL	Comment
	CSR Synopsis	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
BG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000234 BG001233 BG002467

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
	OG000-0.67(-0.79 to -0.55) OG001-0.32(-0.44 to -0.20)

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		Robust Regression	Robust regression using M-estimation with terms for treatment and the metformin stratum and type of insulin, and baseline A1C (%) as a covariate.	<0.001		Mean Difference (Final Values)	-0.34			2-Sided	95	-0.50	-0.19					Superiority or Other

Secondary

Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin

The FAS consisted of all randomized participants receiving insulin in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Posted

Least Squares Mean

95% Confidence Interval

A1C %

Baseline and Week 24

ID	Title	Description
OG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
OG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Units	Counts
Participants

Secondary

Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin

The FAS consisted of all randomized participants receiving insulin alone or in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
OG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Units	Counts

Primary

Number of Participants With One or More Adverse Events

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

The All Patients as Treated (APaT) population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Posted

Number

Participants

Up to Week 26

ID	Title	Description
OG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
OG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Primary

Number of Participants Discontinuing Study Medication Due to an AE

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

The APaT population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Posted

Number

Participants

Up to Week 24

ID	Title	Description
OG000	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
OG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

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	Sitagliptin	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.			4	234	83	234
EG001	Placebo	Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.			9	233	68	233

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk
Angina unstable	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk
Coronary artery disease	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Diabetic foot infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Lung infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Cerebral infarction	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected234 at risk EG0011 events1 affected233 at risk
Diabetic nephropathy	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected234 at risk EG0010 events0 affected233 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood glucose increased	Investigations	MedDRA 17.0	Systematic Assessment	EG00040 events16 affected234 at risk EG00132 events13 affected233 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG00013 events12 affected234 at risk EG00113 events11 affected233 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG000173 events65 affected234 at risk EG001150 events52 affected233 at risk

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.			ClinicalTrialsDisclosure@merck.com

ID	Term
D003924	Diabetes Mellitus, Type 2

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

ID	Term
D000068900	Sitagliptin Phosphate
D007328	Insulin
D008687	Metformin

Ancestor Terms

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines
D011384	Proinsulin
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
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

Units	Counts
Participants	OG000234 OG001233

Units	Counts
Participants	OG000234 OG001233