Trial Outcomes & Findings for Comparison of NN5401 With Insulin Glargine in Insulin Naive Subjects With Type 2 Diabetes (NCT NCT01272193)

NCT ID: NCT01272193

Last Updated: 2017-03-17

Results Overview

Observed change from baseline in HbA1c after 26 weeks of treatment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 296 participants
• Primary outcome timeframe: Week 0, Week 26
• Results posted on: 2017-03-17

Participant Flow

The trial was conducted at 48 sites in Japan.

Subjects continued on not more than 2 oral antidiabetic drugs (excluding sulphonylureas/dipeptyl peptidase-4 [DPP-4] inhibitors/glinides) at the pre-randomisation dose level and dosing frequency.

Participant milestones

Measure	IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Overall Study STARTED	147	149
Overall Study COMPLETED	137	137
Overall Study NOT COMPLETED	10	12

Reasons for withdrawal

Measure	IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Overall Study Adverse Event	1	1
Overall Study Lack of Efficacy	0	3
Overall Study Withdrawal Criteria	1	1
Overall Study Unclassified	8	7

Baseline Characteristics

Comparison of NN5401 With Insulin Glargine in Insulin Naive Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.	Total n=296 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 10.0 • n=5 Participants	61.0 years STANDARD_DEVIATION 9.6 • n=7 Participants	60.5 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	50 Participants n=7 Participants	107 Participants n=5 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	99 Participants n=7 Participants	189 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=7 Participants	8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants
Fasting plasma glucose (FPG)	9.0 mmol/L STANDARD_DEVIATION 1.6 • n=5 Participants	9.1 mmol/L STANDARD_DEVIATION 1.9 • n=7 Participants	9.0 mmol/L STANDARD_DEVIATION 1.7 • n=5 Participants
Body weight	66.2 kg STANDARD_DEVIATION 13.4 • n=5 Participants	66.4 kg STANDARD_DEVIATION 13.3 • n=7 Participants	66.3 kg STANDARD_DEVIATION 13.4 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF).

Observed change from baseline in HbA1c after 26 weeks of treatment

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Change in Glycosylated Haemoglobin (HbA1c)	-1.35 percentage of glycosylated haemoglobin Standard Deviation 0.86	-1.22 percentage of glycosylated haemoglobin Standard Deviation 0.98

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF).

Observed mean increment of the 9-point self-measured plasma glucose profile (SMPG) at the main evening meal

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Mean Increment of 9-point Self Measured Plasma Glucose Profile (SMPG) at the Main Evening Meal	1.4 mmol/L Standard Deviation 4.2	4.7 mmol/L Standard Deviation 3.6

SECONDARY outcome

Timeframe: Week 0 to Week 26 + 7 days follow up

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Rate of Treatment Emergent Adverse Events (AEs) Adverse events (AEs)	334 Events/100 years of patient exposure	368 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Serious AEs	7 Events/100 years of patient exposure	4 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Severe AEs	1 Events/100 years of patient exposure	0 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Moderate AEs	17 Events/100 years of patient exposure	14 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Mild AEs	316 Events/100 years of patient exposure	353 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Fatal AEs	0 Events/100 years of patient exposure	0 Events/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 26 + 7 days follow up

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Observed rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Rate of Confirmed Hypoglycaemic Episodes	191 Episodes/100 years of patient exposure	271 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 26 + 7 days follow up

Population: Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.

Observed rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Rate of Nocturnal Confirmed Hypoglycaemic Episodes	39 Episodes/100 years of patient exposure	53 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF).

Observed change from baseline in body weight after 26 weeks of treatment

Outcome measures

Measure	IDegAsp OD n=147 Participants Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 Participants Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Change in Body Weight	0.7 kg Standard Deviation 2.8	0.7 kg Standard Deviation 2.2

Adverse Events

IDegAsp OD

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

IGlar OD

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	IDegAsp OD n=147 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 participants at risk Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Cardiac disorders Cardiac failure	0.68% 1/147 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/149 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Inguinal hernia	0.68% 1/147 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/149 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Pulmonary tuberculosis	0.68% 1/147 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/149 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Osteitis condensans	0.00% 0/147 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.67% 1/149 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.68% 1/147 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/149 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Cerebral infarction	0.68% 1/147 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.67% 1/149 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Dizziness	0.00% 0/147 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.67% 1/149 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Other adverse events

Measure	IDegAsp OD n=147 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously once daily (OD) either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IDegAsp was given just prior to the largest meal of the day. Insulin doses were individually adjusted.	IGlar OD n=149 participants at risk Insulin glargine (IGlar) was given once daily (OD) according to approved labelling either as monotherapy or in combination with no more than 2 oral antidiabetic drugs (excluding sulphonylureas/DPP-4 inhibitors/glinides). IGlar was given before breakfast or at bedtime but at the same time each day. Insulin doses were individually adjusted.
Eye disorders Diabetic retinopathy	5.4% 8/147 • Number of events 9 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	6.7% 10/149 • Number of events 10 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Nasopharyngitis	22.4% 33/147 • Number of events 39 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	25.5% 38/149 • Number of events 45 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

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