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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01365507
• Collaborator: (none)
• Enrollment: 276
• Locations: 42
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This trial is conducted in Asia and North America. The aim of this trial is to compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily in insulin-naïve subjects with type 2 diabetes mellitus when using two different titration algorithms (dose individually adjusted) as add-on to subject's ongoing treatment with metformin.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin degludec/insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 276 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily in Insulin-naïve Subjects With Type 2 Diabetes Mellitus When Using Two Different Titration Algorithms (BOOST™: SIMPLE USE)
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDegAsp Simple	Drug: insulin degludec/insulin aspart; Insulin degludec/insulin aspart injected subcutaneously (under the skin) once daily. Dose individually adjusted.; Other Names: IDegAsp
Experimental: IDegAsp Step wise	Drug: insulin degludec/insulin aspart; Insulin degludec/insulin aspart injected subcutaneously (under the skin) once daily. Dose individually adjusted.; Other Names: IDegAsp

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated Haemoglobin (HbA1c) [Week 0, week 26]

   Change from baseline in HbA1c after 26 weeks of treatment.

Secondary Outcome Measures

1. Change in Fasting Plasma Glucose (FPG) [Week 0, week 26]

   Change from baseline in FPG after 26 weeks of treatment.

2. Rate of Treatment Emergent Adverse Events (AEs) [Week 0 to Week 26 + 7 days follow up]

   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.

3. Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 26 + 7 days follow up]

   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.

4. Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 26 + 7 days follow up]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes (diagnosed clinically) for 24 weeks or longer prior to randomisation (visit 2)

• Insulin naïve subjects (Allowed are: Previous short term insulin treatment no longer than or equal to 14 days in total; Treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days in total)

• Current treatment: Metformin alone or metformin in any combination of 1 or 2 additional OADs (oral anti-diabetic drug) including an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitors, alpha-glucosidase inhibitors or thiazolidinediones (TZDs) - all with unchanged dosing for at least 12 weeks prior to randomisation (visit 2). Metformin dose, alone or in combination (including fixed combination), must be at least 1000 mg daily

• HbA1c (glycosylated haemoglobin) 7.0-10.0% (both inclusive)

• BMI (Body Mass Index) below or equal to 45 kg/m^2

• Ability and willingness to adhere to the protocol including self measurement of plasma glucose

Exclusion Criteria:

• Treatment with GLP-1 (glucagon like peptide) receptor agonists within the last 12 weeks prior to randomisation (visit 2)

• Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator (trial physician)

• Previous participation in this trial. Participation is defined as randomised. Re-screening is allowed once during the recruitment period

• Known or suspected hypersensitivity to trial products or related products

• The receipt of any investigational drug within 4 weeks prior to randomisation (visit

• Anticipated significant lifestyle changes during the study, e.g. shift work (including permanent night/evening shift workers) as well as highly variable eating habits

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Concord	California	United States	94520-1926
2	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
3	Novo Nordisk Investigational Site	Montclair	California	United States	91763
4	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
5	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
6	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32209-6511
7	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32258
8	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
9	Novo Nordisk Investigational Site	Crestview Hills	Kentucky	United States	41017-3464
10	Novo Nordisk Investigational Site	Madisonville	Kentucky	United States	42431
11	Novo Nordisk Investigational Site	Paducah	Kentucky	United States	42003
12	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
13	Novo Nordisk Investigational Site	North East	Maryland	United States	21901
14	Novo Nordisk Investigational Site	Detroit	Michigan	United States	48235
15	Novo Nordisk Investigational Site	Troy	Michigan	United States	48085-5524
16	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
17	Novo Nordisk Investigational Site	Smithtown	New York	United States	11787
18	Novo Nordisk Investigational Site	Asheboro	North Carolina	United States	27203
19	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
20	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
21	Novo Nordisk Investigational Site	Houston	Texas	United States	77070
22	Novo Nordisk Investigational Site	Lubbock	Texas	United States	79423
23	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
24	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
25	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
26	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	08308
27	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	110-746
28	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	150-950
29	Novo Nordisk Investigational Site	Seoul		Korea, Republic of	158-710
30	Novo Nordisk Investigational Site	Suwon		Korea, Republic of	16247
31	Novo Nordisk Investigational Site	Johor Bahru		Malaysia	80100
32	Novo Nordisk Investigational Site	Kota Bharu, Kelantan		Malaysia	16150
33	Novo Nordisk Investigational Site	Selangor		Malaysia	46150
34	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44650
35	Novo Nordisk Investigational Site	Monterrey		Mexico	64460
36	Novo Nordisk Investigational Site	Bayamon		Puerto Rico	00961
37	Novo Nordisk Investigational Site	Bangkok		Thailand	10400
38	Novo Nordisk Investigational Site	Nakhon Ratchasima		Thailand	30000
39	Novo Nordisk Investigational Site	Antalya		Turkey	07058
40	Novo Nordisk Investigational Site	Istanbul		Turkey	34096
41	Novo Nordisk Investigational Site	Istanbul		Turkey	34718
42	Novo Nordisk Investigational Site	Istanbul		Turkey	34890

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01365507
• Other Study ID Numbers: NN5401-3844; U1111-1117-0558
• First Posted: Jun 3, 2011
• Last Update Posted: Mar 17, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin Aspart

Study Results

Participant Flow

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

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	136	140
Exposed	134	140
COMPLETED	127	131
NOT COMPLETED	9	9

Baseline Characteristics

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	136	140	276
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.0 (9.4)	55.8 (9.7)	56.4 (9.5)
Sex: Female, Male (Count of Participants)
Female	59 43.4%	84 60%	143 51.8%
Male	77 56.6%	56 40%	133 48.2%
Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.3 (0.8)	8.2 (0.8)	8.3 (0.8)
Fasting plasma glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	8.9 (2.4)	9.0 (2.3)	8.9 (2.4)

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c)
Description	Change from baseline in HbA1c after 26 weeks of treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Measure Participants	136	140
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-1.33 (1.03)	-1.09 (0.82)

2. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Description	Change from baseline in FPG after 26 weeks of treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Measure Participants	135	139
Mean (Standard Deviation) [mmol/L]	-2.99 (3.03)	-2.73 (2.91)

3. Secondary Outcome

Title	Rate of Treatment Emergent Adverse Events (AEs)
Description	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.
Time Frame	Week 0 to Week 26 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Measure Participants	134	140
Adverse events (AEs)	226	342
Serious AEs	2	13
Severe AEs	3	3
Moderate AEs	68	112
Mild AEs	155	228
Fatal AEs	0	0

4. Secondary Outcome

Title	Rate of Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 26 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Measure Participants	134	140
Number [Episodes/100 years of patient exposure]	326	207

5. Secondary Outcome

Title	Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 26 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp Simple	IDegAsp Step Wise
Arm/Group Description	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.	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.
Measure Participants	134	140
Number [Episodes/100 years of patient exposure]	52	41

Adverse Events

Time Frame	The adverse events were collected in a time frame of 26 weeks + 7 days follow up.
Adverse Event Reporting Description	The safety analysis set included all subjects who received at least one dose of the investigational product.
Arm/Group Title	IDegAsp Simple		IDegAsp Step Wise
Arm/Group Description	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.		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.
All Cause Mortality
	IDegAsp Simple		IDegAsp Step Wise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDegAsp Simple		IDegAsp Step Wise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/134 (0.7%)		6/140 (4.3%)
Gastrointestinal disorders
Diverticular perforation	1/134 (0.7%)	1	0/140 (0%)	0
Rectal haemorrhage	0/134 (0%)	0	1/140 (0.7%)	1
Hepatobiliary disorders
Cholelithiasis	0/134 (0%)	0	1/140 (0.7%)	1
Infections and infestations
Gastroenteritis	0/134 (0%)	0	1/140 (0.7%)	1
Injury, poisoning and procedural complications
Facial bones fracture	0/134 (0%)	0	1/140 (0.7%)	1
Subcutaneous haematoma	0/134 (0%)	0	1/140 (0.7%)	1
Nervous system disorders
Cerebral infarction	0/134 (0%)	0	1/140 (0.7%)	1
Convulsion	0/134 (0%)	0	1/140 (0.7%)	1
Dizziness postural	0/134 (0%)	0	1/140 (0.7%)	1
Thalamic infarction	0/134 (0%)	0	1/140 (0.7%)	1
Other (Not Including Serious) Adverse Events
	IDegAsp Simple		IDegAsp Step Wise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/134 (14.9%)		26/140 (18.6%)
Infections and infestations
Nasopharyngitis	8/134 (6%)	10	11/140 (7.9%)	13
Upper respiratory tract infection	12/134 (9%)	15	15/140 (10.7%)	18

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.