A Trial Comparing the Safety and Efficacy of Semaglutide... | NCT02254291

ID	Type	Description	Link
U1111-1140-5334	Other Identifier	WHO
JapicCTI-142663	Registry Identifier	JAPIC

Label	Type	Intervention Names
Semaglutide 0.5 mg	Experimental	Drug: semaglutide
Semaglutide 1.0 mg	Experimental	Drug: semaglutide
Sitagliptin 100 mg	Active Comparator	Drug: sitagliptin

Name	Type	Description	Arm Group Labels	Other Names
semaglutide	Drug	Once weekly doses of 0.5 mg semaglutide after an initial dose escalation step of 0.25 mg (4 weeks). Total duration of treatment is 30 weeks. Administered subcutaneously (s.c. under the skin).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs)	An adverse events (AEs) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).	Weeks 0-30

Secondary Outcomes

Measure	Description	Time Frame
Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, age 20 years or older at the time of signing informed consent
Glycated hemoglobin (HbA1c) between 6.5% and 9.5% (48-80 mmol/mol) (both inclusive) for subjects treated with oral antidiabetic drug (OAD) monotherapy and between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive) for subjects treated with diet and exercise therapy at screening
Japanese subjects diagnosed with type 2 diabetes who are: a) on stable OAD monotherapy at a half-maximum dose or below according to the approved Japanese labelling in addition to diet and exercise therapy for at least 30 days prior to screening (week -8) (For metformin only: the maximum dose of 750 mg/day is allowed except for METGLUCO®. For METGLUCO®, the allowable half-max dose of 1125 mg/day must be applied.). 'Stable' is defined as unchanged medication and unchanged dose, or b) on stable diet and exercise therapy for at least 30 days prior to screening (week -2)

Exclusion Criteria:

Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (e.g. abstinence, diaphragm, condom [by the partner], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5-week follow-up period
Treatment with once-weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days prior to screening
Treatment with any glucose lowering agent(s) (except for pre-trial OAD for subject treated with OAD monotherapy) in a period of 60 days prior to screening. An exception is short-term treatment (7 days or less in total) with insulin in connection with inter-current illness
Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol
History of chronic or idiopathic acute pancreatitis
Screening calcitonin value of 50 ng/L (pg/mL) or greater
Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)
Impaired renal function defined as estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version)
Acute coronary or cerebrovascular event within 90 days before randomisation
Heart failure, New York Heart Association (NYHA) class IV

Name	Affiliation	Role
Global Clinical Registry GCR, 1452	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Asahikawa-shi, Hokkaido		070 0002	Japan
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
28786547	Result	Seino Y, Terauchi Y, Osonoi T, Yabe D, Abe N, Nishida T, Zacho J, Kaneko S. Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. Diabetes Obes Metab. 2018 Feb;20(2):378-388. doi: 10.1111/dom.13082. Epub 2017 Oct 5.
32998732	Derived

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
BG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
BG002	Sitagliptin	The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Treatment Emergent Adverse Events (TEAEs)

An adverse events (AEs) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

The safety analysis set (SAS) included all subjects receiving at least one dose of trial product and subjects contributed to the evaluation "as treated".

Posted

Number

Number of events

Weeks 0-30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
OG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.
OG002	Sitagliptin	The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.

Units	Counts
Participants	OG000103 OG001102 OG002103

Title

Denominators

Categories

Title	Measurements
	OG000228 OG001197 OG002186

Secondary

Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes

Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

The safety analysis set (SAS) included all subjects receiving at least one dose of trial product and subjects contributed to the evaluation "as treated".

Posted

Number

Number of episodes

Weeks 0-30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.

Secondary

Change in Glycosylated Haemoglobin A1c (HbA1c)

Mean changes in HbA1c values from baseline after 30 weeks of treatment. Changes in HbA1c were analysed using a mixed model for repeated measurements (MMRM) with treatment and pre-trial treatment at screening as fixed factors and baseline value as covariate. The data were analysed for the "on-treatment without rescue medication" observation period which includes observations noted at or after the date of first dose of randomised treatment and not after the last dose of the trial product (+ a 7-day visit window) or initiation of rescue medication.

The full analysis set (FAS) included all randomised subjects who have received at least one dose of trial product. All subjects contributed to the statistical model of the data analysis, but not all subjects had a value at week 30.

Posted

Least Squares Mean

Standard Error

Percentage of glycosylated haemoglobin

Week 0 and week 30

ID	Title	Description
OG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Semaglutide 0.5 mg	Subjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly maintenance dose for 26 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	6	103	53	103
EG001	Semaglutide 1.0 mg	Subjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a duration of 30 weeks. Subjects followed a fixed dose escalation pattern to improve tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to 0.5 mg once weekly for 4 weeks, and finally escalated to 1.0 mg once weekly maintenance dose for 22 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. For subjects previously treated with OAD monotherapy, their 8-week pre-trial OAD was washed out before randomisation. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	2	102	46	102
EG002	Sitagliptin	The subjects in this arm received oral fixed dose of sitagliptin 100 mg tablet once daily for a duration of 30 weeks. For subjects previously treated with OAD monotherapy, their pre-trial OAD was washed out before randomisation. Doses of sitagliptin were not changed throughout the trial. All subjects continued their pre-trial treatment of diet and exercise therapy throughout the trial.	2	103	36	103

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected102 at risk EG0020 events0 affected103 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected102 at risk EG0020 events0 affected103 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected103 at risk EG0010 events0 affected102 at risk EG0021 events1 affected103 at risk
Herpes zoster	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Loss of consciousness	Nervous system disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Pancreatic carcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0000 events0 affected103 at risk EG0010 events0 affected102 at risk EG0021 events1 affected103 at risk
Pneumonia	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk
Postrenal failure	Renal and urinary disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected103 at risk EG0010 events0 affected102 at risk EG0021 events1 affected103 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected102 at risk EG0020 events0 affected103 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

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

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0004 events4 affected103 at risk EG0018 events7 affected102 at risk EG0020 events0 affected103 at risk
Amylase increased	Investigations	MedDRA 18	Systematic Assessment	EG0007 events6 affected103 at risk EG0012 events2 affected102 at risk EG0022 events2 affected103 at risk
Constipation	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00016 events15 affected103 at risk EG00112 events12 affected102 at risk EG0024 events4 affected103 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18	Systematic Assessment	EG00010 events9 affected103 at risk EG0018 events8 affected102 at risk EG0020 events0 affected103 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0009 events7 affected103 at risk EG00114 events9 affected102 at risk EG0023 events2 affected103 at risk
Lipase increased	Investigations	MedDRA 18	Systematic Assessment	EG00012 events10 affected103 at risk EG0018 events7 affected102 at risk EG0025 events4 affected103 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG00021 events17 affected103 at risk EG00122 events18 affected102 at risk EG00242 events30 affected103 at risk
Nausea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00012 events11 affected103 at risk EG00122 events13 affected102 at risk EG0020 events0 affected103 at risk