Trial Outcomes & Findings for Efficacy and Safety of Insulin Degludec/Insulin Aspart in Insulin-naïve Subjects With Type 2 Diabetes Using Two Dosing Regimens (NCT NCT01365507)

NCT ID: NCT01365507

Last Updated: 2017-03-17

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 276 participants
• Primary outcome timeframe: Week 0, week 26
• Results posted on: 2017-03-17

Participant Flow

This trial was conducted at 38 sites in 6 countries: Malaysia, Mexico, South Korea, Thailand, Turkey and the United States (U.S.).

Subjects continued their metformin monotherapy or metformin in any combination with 1 or 2 additional oral antidiabetic drugs including an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV inhibitors, α-glucosidase inhibitors, thiazolidinediones, all with unchanged dosing for at least 12 weeks prior to randomisation.

Participant milestones

Measure	IDegAsp Simple Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Overall Study STARTED	136	140
Overall Study Exposed	134	140
Overall Study COMPLETED	127	131
Overall Study NOT COMPLETED	9	9

Reasons for withdrawal

Measure	IDegAsp Simple Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Overall Study Withdrawal Criteria	8	5
Overall Study Unclassified	1	4

Baseline Characteristics

Efficacy and Safety of Insulin Degludec/Insulin Aspart in Insulin-naïve Subjects With Type 2 Diabetes Using Two Dosing Regimens

Baseline characteristics by cohort

Measure	IDegAsp Simple n=136 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.	Total n=276 Participants Total of all reporting groups
Age, Continuous	57.0 years STANDARD_DEVIATION 9.4 • n=5 Participants	55.8 years STANDARD_DEVIATION 9.7 • n=7 Participants	56.4 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	84 Participants n=7 Participants	143 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	56 Participants n=7 Participants	133 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=7 Participants	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants
Fasting plasma glucose (FPG)	8.9 mmol/L STANDARD_DEVIATION 2.4 • n=5 Participants	9.0 mmol/L STANDARD_DEVIATION 2.3 • n=7 Participants	8.9 mmol/L STANDARD_DEVIATION 2.4 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

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

Change from baseline in HbA1c after 26 weeks of treatment.

Outcome measures

Measure	IDegAsp Simple n=136 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Change in Glycosylated Haemoglobin (HbA1c)	-1.33 percentage of glycosylated haemoglobin Standard Deviation 1.03	-1.09 percentage of glycosylated haemoglobin Standard Deviation 0.82

SECONDARY outcome

Timeframe: Week 0, week 26

Population: The full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). For 2 subjects baseline values were missing, hence not included in the analysis.

Change from baseline in FPG after 26 weeks of treatment.

Outcome measures

Measure	IDegAsp Simple n=135 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=139 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Change in Fasting Plasma Glucose (FPG)	-2.99 mmol/L Standard Deviation 3.03	-2.73 mmol/L Standard Deviation 2.91

SECONDARY outcome

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

Population: The safety analysis set included all subjects who received at least one dose of the investigational product.

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 Simple n=134 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Rate of Treatment Emergent Adverse Events (AEs) Adverse events (AEs)	226 Events/100 years of patient exposure	342 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Serious AEs	2 Events/100 years of patient exposure	13 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Severe AEs	3 Events/100 years of patient exposure	3 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
Rate of Treatment Emergent Adverse Events (AEs) Moderate AEs	68 Events/100 years of patient exposure	112 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Mild AEs	155 Events/100 years of patient exposure	228 Events/100 years of patient exposure

SECONDARY outcome

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

Population: The safety analysis set included all subjects who received at least one dose of the investigational product.

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 Simple n=134 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Rate of Confirmed Hypoglycaemic Episodes	326 Episodes/100 years of patient exposure	207 Episodes/100 years of patient exposure

SECONDARY outcome

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

Population: The safety analysis set included all subjects who received at least one dose of the investigational product.

Rate of nocturnal 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 Simple n=134 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Rate of Nocturnal Confirmed Hypoglycaemic Episodes	52 Episodes/100 years of patient exposure	41 Episodes/100 years of patient exposure

Adverse Events

IDegAsp Simple

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

IDegAsp Step Wise

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	IDegAsp Simple n=134 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Gastrointestinal disorders Diverticular perforation	0.75% 1/134 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.00% 0/140 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Hepatobiliary disorders Cholelithiasis	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Infections and infestations Gastroenteritis	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Nervous system disorders Cerebral infarction	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Nervous system disorders Convulsion	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Nervous system disorders Dizziness postural	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Nervous system disorders Thalamic infarction	0.00% 0/134 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	0.71% 1/140 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.

Other adverse events

Measure	IDegAsp Simple n=134 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (3-4 days intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDegAsp Step Wise n=140 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (at least 5 days intervals between doses) with pre-trial metformin according to step wise titration algorithm: self-titration was performed once weekly based on the lowest value of three pre-breakfast SMPG values measured on three consecutive days, the two days prior to and on the day of insulin titration.
Infections and infestations Nasopharyngitis	6.0% 8/134 • Number of events 10 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	7.9% 11/140 • Number of events 13 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.
Infections and infestations Upper respiratory tract infection	9.0% 12/134 • Number of events 15 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.	10.7% 15/140 • Number of events 18 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product.

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