Trial Outcomes & Findings for Comparing the Efficacy and Safety of NN1250 Once Daily When Titrated Using 2 Different Algorithms in Insulin naïve Subjects With Type 2 Diabetes Mellitus (NCT NCT01326026)

NCT ID: NCT01326026

Last Updated: 2017-03-06

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 222 participants
• Primary outcome timeframe: Week 0, Week 26
• Results posted on: 2017-03-06

Participant Flow

The trial was conducted at 43 sites in 4 countries: Finland (5), Germany (6), Spain (6) and United States of America (26).

Subjects continued on metformin treatment at the pre-randomisation dose level and dosing frequency.

Participant milestones

Measure	IDeg Simple Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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	111	111
Overall Study Exposed	110	111
Overall Study COMPLETED	99	98
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Measure	IDeg Simple Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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 Adverse Event	4	3
Overall Study Withdrawal Criteria	5	7
Overall Study Other	3	3

Baseline Characteristics

Comparing the Efficacy and Safety of NN1250 Once Daily When Titrated Using 2 Different Algorithms in Insulin naïve Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	IDeg Simple n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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=222 Participants Total of all reporting groups
Age, Continuous	59.4 years STANDARD_DEVIATION 9.5 • n=5 Participants	58.5 years STANDARD_DEVIATION 11.1 • n=7 Participants	58.9 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	36 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	75 Participants n=7 Participants	143 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting plasma glucose (FPG)	9.3 mmol/L STANDARD_DEVIATION 2.6 • n=5 Participants	9.4 mmol/L STANDARD_DEVIATION 2.8 • n=7 Participants	9.4 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).

Change from baseline in HbA1c after 26 weeks of treatment.

Outcome measures

Measure	IDeg Simple n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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)	-1.09 percentage of glycosylated haemoglobin Standard Deviation 1.05	-0.93 percentage of glycosylated haemoglobin Standard Deviation 0.97

SECONDARY 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). For 7 subjects baseline values were missing.

Change from baseline in FPG after 26 weeks of treatment.

Outcome measures

Measure	IDeg Simple n=108 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=107 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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)	-3.27 mmol/L Standard Deviation 3.56	-2.68 mmol/L Standard Deviation 3.50

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	IDeg Simple n=110 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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)	346 Events/100 years of patient exposure	379 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Serious AEs	15 Events/100 years of patient exposure	15 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Severe AEs	15 Events/100 years of patient exposure	10 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Moderate AEs	69 Events/100 years of patient exposure	79 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Mild AEs	262 Events/100 years of patient exposure	291 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Fatal AEs	0 Events/100 years of patient exposure	2 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.

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 are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Measure	IDeg Simple n=110 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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	160 Episodes/100 years of patient exposure	117 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.

Observed 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 are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

Outcome measures

Measure	IDeg Simple n=110 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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	21 Episodes/100 years of patient exposure	10 Episodes/100 years of patient exposure

Adverse Events

IDeg Simple

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

IDeg Step Wise

Serious events: 7 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	IDeg Simple n=110 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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.
Cardiac disorders Acute myocardial infarction	1.8% 2/110 • Number of events 2 • 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% 0/111 • 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.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/110 • 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.	0.90% 1/111 • 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.
Cardiac disorders Atrioventricular block complete	0.91% 1/110 • 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% 0/111 • 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.
Cardiac disorders Coronary artery occlusion	0.00% 0/110 • 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.	0.90% 1/111 • 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.
Cardiac disorders Coronary artery stenosis	0.91% 1/110 • 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% 0/111 • 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.
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia	0.91% 1/110 • 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% 0/111 • 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.
Ear and labyrinth disorders Vertigo	0.91% 1/110 • 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% 0/111 • 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 Retroperitoneal haematoma	0.91% 1/110 • 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% 0/111 • 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 Bronchitis	0.00% 0/110 • 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.	0.90% 1/111 • 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 Accidental overdose	0.00% 0/110 • 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.	0.90% 1/111 • 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 Contusion	0.00% 0/110 • 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.	0.90% 1/111 • 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.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/110 • 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.	0.90% 1/111 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Astrocytoma	0.91% 1/110 • 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% 0/111 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/110 • 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.	0.90% 1/111 • 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.
Psychiatric disorders Panic attack	0.00% 0/110 • 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.	0.90% 1/111 • 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	IDeg Simple n=110 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours intervals between doses) with pre-trial metformin according to simple titration algorithm: self-titration was performed once weekly based upon a single pre-breakfast self measured plasma glucose (SMPG) value measured on the day of insulin titration.	IDeg Step Wise n=111 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (approximately 8-40 hours 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	9.1% 10/110 • 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.	6.3% 7/111 • Number of events 8 • 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 Headache	7.3% 8/110 • Number of events 8 • 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.	7.2% 8/111 • Number of events 14 • 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.

Additional Information

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• 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.
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