Trial Outcomes & Findings for Comparison of NN5401 With Insulin Glargine, Both in Combination With Oral Antidiabetic Drugs, in Subjects With Type 2 Diabetes (NCT NCT01045447)

NCT ID: NCT01045447

Last Updated: 2017-03-20

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

465 participants

Primary outcome timeframe

Week 0, Week 26

Results posted on

2017-03-20

Participant Flow

The trial was conducted at 61 sites in 9 countries: Croatia (2 sites), France (4), India (8), Poland (4), South Africa (3), Republic of Korea (6), Sweden (5), Turkey (5) and United States of America (24).

Participant milestones

Participant milestones
Measure	IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Overall Study STARTED	232	233
Overall Study Exposed	230	233
Overall Study COMPLETED	196	205
Overall Study NOT COMPLETED	36	28

Reasons for withdrawal

Reasons for withdrawal
Measure	IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	3	1
Overall Study Protocol Violation	6	3
Overall Study Withdrawal Criteria	10	10
Overall Study Unclassified	17	13

Baseline Characteristics

Comparison of NN5401 With Insulin Glargine, Both in Combination With Oral Antidiabetic Drugs, in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDegAsp OD n=230 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD n=233 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.	Total n=463 Participants Total of all reporting groups
Age, Continuous	57.8 years STANDARD_DEVIATION 9.5 • n=5 Participants	58.4 years STANDARD_DEVIATION 10.1 • n=7 Participants	58.1 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	106 Participants n=7 Participants	201 Participants n=5 Participants
Sex: Female, Male Male	135 Participants n=5 Participants	127 Participants n=7 Participants	262 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 • n=5 Participants	8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.0 • n=7 Participants	8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting plasma glucose (FPG)	8.0 mmol/L STANDARD_DEVIATION 2.5 • n=5 Participants	7.8 mmol/L STANDARD_DEVIATION 2.8 • n=7 Participants	7.9 mmol/L STANDARD_DEVIATION 2.7 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). Two subjects withdrew prior to exposure to trial drug, hence excluded from the FAS.

Change from baseline in HbA1c after 26 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDegAsp OD n=230 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD n=233 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Change in Glycosylated Haemoglobin (HbA1c)	-0.98 percentage of glycosylated haemoglobin Standard Deviation 1.01	-1.00 percentage of glycosylated haemoglobin Standard Deviation 1.06

SECONDARY outcome

Timeframe: Week 26

Mean of SMPG after 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.

Outcome measures

Outcome measures
Measure	IDegAsp OD n=220 Participants Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD n=220 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)	8.1 mmol/L Standard Deviation 2.0	8.4 mmol/L Standard Deviation 2.0

Adverse Events

IDegAsp OD

Serious events: 10 serious events

Other events: 51 other events

Deaths: 0 deaths

IGlar OD

Serious events: 8 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDegAsp OD n=230 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD n=233 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Gastrointestinal disorders Diarrhoea	5.2% 12/230 • 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 or its comparator.	5.6% 13/233 • 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 or its comparator.
General disorders Oedema peripheral	2.2% 5/230 • Number of events 5 • 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 or its comparator.	5.2% 12/233 • Number of events 12 • 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 or its comparator.
Infections and infestations Nasopharyngitis	7.4% 17/230 • Number of events 21 • 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 or its comparator.	7.7% 18/233 • Number of events 21 • 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 or its comparator.
Infections and infestations Upper respiratory tract infection	4.8% 11/230 • Number of events 12 • 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 or its comparator.	5.6% 13/233 • 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 or its comparator.
Nervous system disorders Headache	8.7% 20/230 • Number of events 26 • 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 or its comparator.	8.2% 19/233 • Number of events 26 • 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 or its comparator.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
Publication restrictions are in place

Restriction type: OTHER

Measure	IDegAsp OD n=230 participants at risk Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor.	IGlar OD n=233 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor.
Cardiac disorders Angina pectoris	0.43% 1/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Cardiac disorders Atrial fibrillation	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Cardiac disorders Coronary artery stenosis	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Cardiac disorders Myocardial infarction	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Eye disorders Cataract	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Gastrointestinal disorders Anal fistula	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Gastrointestinal disorders Inguinal hernia	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
General disorders Chest pain	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
General disorders Pyrexia	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Infections and infestations Gastroenteritis	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Infections and infestations Laryngitis	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Infections and infestations Pneumonia	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Injury, poisoning and procedural complications Ankle fracture	0.43% 1/230 • 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 or its comparator.	0.00% 0/233 • 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 or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.43% 1/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.
Vascular disorders Haemorrhage	0.00% 0/230 • 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 or its comparator.	0.43% 1/233 • 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 or its comparator.