BEGIN™: Comparison of NN1250 With Insulin Glargine in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01076647
• Collaborator: (none)
• Enrollment: 467
• Locations: 105
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial was conducted in Europe and North America. The aim of this clinical trial was to compare NN1250 (insulin degludec (IDeg)), a soluble insulin basal analogue (SIBA), with insulin glargine (IGlar), as add-on to subject's ongoing treatment with metformin and/or DPP-4 (dipeptyl peptidase 4) inhibitors, in patients with type 2 diabetes being treated with oral anti-diabetic drugs (OADs).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 467 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week Randomised, Confirmatory, Controlled, Open Label, Multicentre, Multinational Treat-to-target Trial Comparing the Efficacy and Safety of SIBA 200 U/ml Three Times Weekly Injected in the Evening and Insulin Glargine Once Daily in a Population of Insulin naïve Subjects With Type 2 Diabetes Mellitus Currently Treated With OADs Qualifying for Intensified Treatment (BEGIN™: EASY™)
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDeg 3TW	Drug: insulin degludec; Will be injected subcutaneously (under the skin) once daily three times weekly.
Active Comparator: IGlar OD	Drug: insulin glargine; Will be injected subcutaneously (under the skin) once daily administered at the same time each day.

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 Body Weight [Week 0, Week 26]

   Change from baseline in body weight after 26 weeks of treatment

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 at least 6 months

• Insulin naïve subjects (allowed are: previous short term insulin treatment up to 14 days; treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days)

• Current treatment: metformin monotherapy or metformin in any combination with insulin secretagogues (sulphonylurea (SU) or glinide), DPP-4 inhibitor, alpha-glucosidase-inhibitor (acarbose) with unchanged dosing for at least 3 months prior to visit 1 with the minimum doses stated: -Metformin: alone or in combination (including fixed combination) 1500 mg daily or maximum tolerated dose (at least 1000 mg daily)-Insulin secretagogue (sulfonylurea (SU) or glinide): minimum half of the daily maximal dose according to local labelling -DPP-4 inhibitor: minimum half of the daily maximal dose according to local labelling -alpha-glucosidase-inhibitor (acarbose): minimum half of the daily maximal dose or maximum tolerated dose

• HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis

• BMI (Body Mass Index) below or equal to 45.0 kg/m^2

Exclusion Criteria:

• Use within the last 3 months prior to Visit 1 of: Thiazoledinediones (TZDs), Exenatide or Liraglutide

• Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty

• Uncontrolled treated/untreated severe hypertension (systolic blood pressure at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg)

• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements

• Cancer and medical history of cancer hereof (except basal cell skin cancer or squamous cell skin cancer)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35216
2	Novo Nordisk Investigational Site	Peoria	Arizona	United States	85381
3	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85712
4	Novo Nordisk Investigational Site	Beverly Hills	California	United States	90211
5	Novo Nordisk Investigational Site	Escondido	California	United States	92025
6	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
7	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
8	Novo Nordisk Investigational Site	Los Banos	California	United States	93635
9	Novo Nordisk Investigational Site	Monterey	California	United States	93940
10	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
11	Novo Nordisk Investigational Site	Pasadena	California	United States	91105
12	Novo Nordisk Investigational Site	Redondo Beach	California	United States	90277
13	Novo Nordisk Investigational Site	San Mateo	California	United States	94401
14	Novo Nordisk Investigational Site	Tarzana	California	United States	91356-3551
15	Novo Nordisk Investigational Site	Tustin	California	United States	92780
16	Novo Nordisk Investigational Site	Denver	Colorado	United States	80209
17	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
18	Novo Nordisk Investigational Site	Boynton Beach	Florida	United States	33472
19	Novo Nordisk Investigational Site	DeLand	Florida	United States	32720
20	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34741
21	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
22	Novo Nordisk Investigational Site	Orange Park	Florida	United States	32073
23	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
24	Novo Nordisk Investigational Site	Tampa	Florida	United States	33613
25	Novo Nordisk Investigational Site	West Palm Beach	Florida	United States	33401
26	Novo Nordisk Investigational Site	Conyers	Georgia	United States	30094-5965
27	Novo Nordisk Investigational Site	Dunwoody	Georgia	United States	30338
28	Novo Nordisk Investigational Site	Arlington Heights	Illinois	United States	60004-2315
29	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
30	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60622
31	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62711
32	Novo Nordisk Investigational Site	Wichita	Kansas	United States	67205
33	Novo Nordisk Investigational Site	Crestview Hills	Kentucky	United States	41017-3464
34	Novo Nordisk Investigational Site	Madisonville	Kentucky	United States	42431
35	Novo Nordisk Investigational Site	Metairie	Louisiana	United States	70002
36	Novo Nordisk Investigational Site	Glen Burnie	Maryland	United States	21061
37	Novo Nordisk Investigational Site	Reisterstown	Maryland	United States	21136-2516
38	Novo Nordisk Investigational Site	Silver Spring	Maryland	United States	20910
39	Novo Nordisk Investigational Site	Ann Arbor	Michigan	United States	48106-0482
40	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
41	Novo Nordisk Investigational Site	Smithtown	New York	United States	11787
42	Novo Nordisk Investigational Site	Staten Island	New York	United States	10301
43	Novo Nordisk Investigational Site	Asheville	North Carolina	United States	28801
44	Novo Nordisk Investigational Site	Burlington	North Carolina	United States	27215-8700
45	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
46	Novo Nordisk Investigational Site	Winston Salem	North Carolina	United States	27103
47	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45255
48	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45406
49	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16601
50	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
51	Novo Nordisk Investigational Site	Harrisburg	Pennsylvania	United States	17112-1900
52	Novo Nordisk Investigational Site	Langhorne	Pennsylvania	United States	19047
53	Novo Nordisk Investigational Site	East Providence	Rhode Island	United States	02914
54	Novo Nordisk Investigational Site	Newberry	South Carolina	United States	29108-2249
55	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
56	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
57	Novo Nordisk Investigational Site	Arlington	Texas	United States	76014
58	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
59	Novo Nordisk Investigational Site	Houston	Texas	United States	77025
60	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
61	Novo Nordisk Investigational Site	Ogden	Utah	United States	84403
62	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84102
63	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84107
64	Novo Nordisk Investigational Site	Chesapeake	Virginia	United States	23320
65	Novo Nordisk Investigational Site	Seattle	Washington	United States	98105
66	Novo Nordisk Investigational Site	Spokane	Washington	United States	99218
67	Novo Nordisk Investigational Site	Burgas		Bulgaria	8000
68	Novo Nordisk Investigational Site	Ruse		Bulgaria	7000
69	Novo Nordisk Investigational Site	Sofia		Bulgaria	1606
70	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6000
71	Novo Nordisk Investigational Site	Chilliwack	British Columbia	Canada	V2P 4M9
72	Novo Nordisk Investigational Site	Ottawa	Ontario	Canada	K1K 4L2
73	Novo Nordisk Investigational Site	Thornhill	Ontario	Canada	L4J 8L7
74	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M5C 2T2
75	Novo Nordisk Investigational Site	Quebec		Canada	G1N 4V3
76	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G5
77	Novo Nordisk Investigational Site	Quebec		Canada	G3K 2P8
78	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9		France	85295
79	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
80	Novo Nordisk Investigational Site	Le Creusot		France	71200
81	Novo Nordisk Investigational Site	Nanterre		France	92014
82	Novo Nordisk Investigational Site	Narbonne		France	11108
83	Novo Nordisk Investigational Site	Nimes		France	30006
84	Novo Nordisk Investigational Site	Paris		France	75877
85	Novo Nordisk Investigational Site	Venissieux		France	69200
86	Novo Nordisk Investigational Site	Budapest		Hungary	1125
87	Novo Nordisk Investigational Site	Debrecen		Hungary	4043
88	Novo Nordisk Investigational Site	Eger		Hungary	3300
89	Novo Nordisk Investigational Site	Gyula		Hungary	5700
90	Novo Nordisk Investigational Site	Kaposvar		Hungary	H-7400
91	Novo Nordisk Investigational Site	Szeged		Hungary	H-6720
92	Novo Nordisk Investigational Site	Amsterdam		Netherlands	1105 AZ
93	Novo Nordisk Investigational Site	Beek		Netherlands	6191JW
94	Novo Nordisk Investigational Site	Etten-Leur		Netherlands	4872 LP
95	Novo Nordisk Investigational Site	Hengelo		Netherlands	7555 DL
96	Novo Nordisk Investigational Site	Hoogeveen		Netherlands	7909 AA
97	Novo Nordisk Investigational Site	Lieshout		Netherlands	5737 CB
98	Novo Nordisk Investigational Site	Utrecht		Netherlands	3582 KE
99	Novo Nordisk Investigational Site	Zwijndrecht		Netherlands	3331 LZ
100	Novo Nordisk Investigational Site	Oradea	Bihor	Romania	410469
101	Novo Nordisk Investigational Site	Bacau		Romania	600164
102	Novo Nordisk Investigational Site	Botosani		Romania	710224
103	Novo Nordisk Investigational Site	Bucharest		Romania	010816
104	Novo Nordisk Investigational Site	Galati		Romania	800578
105	Novo Nordisk Investigational Site	Satu Mare		Romania	440055

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: NCT01076647
• Other Study ID Numbers: NN1250-3718; 2009-011399-31; U1111-1112-8770
• First Posted: Feb 26, 2010
• Last Update Posted: Mar 6, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 89 sites in 7 countries: Bulgaria, Canada, France, Hungary, Netherlands, Romania, and United States.

Arm/Group Title	IDeg 3TW	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.	Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.
Period Title: Overall Study
STARTED	233	234
COMPLETED	208	209
NOT COMPLETED	25	25

Baseline Characteristics

Arm/Group Title	IDeg 3TW	IGlar OD	Total
Arm/Group Description	Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.	Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.	Total of all reporting groups
Overall Participants	233	234	467
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (9.6)	57.5 (10.7)	57.4 (10.2)
Sex: Female, Male (Count of Participants)
Female	101 43.3%	99 42.3%	200 42.8%
Male	132 56.7%	135 57.7%	267 57.2%
Glycosylated haemoglobin (HbaA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.3 (0.8)	8.3 (0.8)	8.3 (0.8)
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	92.3 (18.3)	91.4 (18.7)	91.8 (18.5)

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 is imputed using last observation carried forward (LOCF).

Arm/Group Title	IDeg 3TW	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.	Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.
Measure Participants	233	234
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-1.05 (0.94)	-1.36 (0.95)

2. Secondary Outcome

Title	Change in Body Weight
Description	Change from baseline in body weight after 26 weeks of treatment
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Arm/Group Title	IDeg 3TW	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.	Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.
Measure Participants	233	234
Mean (Standard Deviation) [kg]	0.8 (3.9)	0.5 (3.7)

Adverse Events

Time Frame	The adverse events were collected in a time frame of 26 weeks + 7 days follow up
Adverse Event Reporting Description	Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title	IDeg 3TW		IGlar OD
Arm/Group Description	Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.		Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks.
All Cause Mortality
	IDeg 3TW		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDeg 3TW		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/233 (5.6%)		12/234 (5.1%)
Blood and lymphatic system disorders
Lymphadenopathy	1/233 (0.4%)	1	0/234 (0%)	0
Cardiac disorders
Angina pectoris	0/233 (0%)	0	1/234 (0.4%)	1
Angina unstable	1/233 (0.4%)	1	0/234 (0%)	0
Atrial fibrillation	1/233 (0.4%)	1	1/234 (0.4%)	1
Cardiac asthma	0/233 (0%)	0	1/234 (0.4%)	1
Tachycardia	1/233 (0.4%)	1	0/234 (0%)	0
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/233 (0%)	0	1/234 (0.4%)	1
Periodontitis	1/233 (0.4%)	1	0/234 (0%)	0
General disorders
Chest pain	0/233 (0%)	0	1/234 (0.4%)	1
Infections and infestations
Erysipelas	0/233 (0%)	0	2/234 (0.9%)	2
Injury, poisoning and procedural complications
Road traffic accident	1/233 (0.4%)	1	0/234 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	1/233 (0.4%)	1	0/234 (0%)	0
Hyponatraemic syndrome	1/233 (0.4%)	1	0/234 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder	0/233 (0%)	0	1/234 (0.4%)	1
Musculoskeletal pain	0/233 (0%)	0	1/234 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/233 (0.4%)	1	0/234 (0%)	0
Malignant melanoma	1/233 (0.4%)	1	0/234 (0%)	0
Nervous system disorders
Facial paresis	0/233 (0%)	0	1/234 (0.4%)	1
Presyncope	0/233 (0%)	0	1/234 (0.4%)	1
Vertebrobasilar insufficiency	0/233 (0%)	0	1/234 (0.4%)	1
Vertigo CNS origin	1/233 (0.4%)	1	0/234 (0%)	0
Psychiatric disorders
Depression	0/233 (0%)	0	1/234 (0.4%)	1
Panic disorder	0/233 (0%)	0	1/234 (0.4%)	1
Reproductive system and breast disorders
Ovarian cyst	0/233 (0%)	0	1/234 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/233 (0.4%)	1	0/234 (0%)	0
Surgical and medical procedures
Lithotripsy	1/233 (0.4%)	1	0/234 (0%)	0
Vascular disorders
Arteriosclerosis	0/233 (0%)	0	1/234 (0.4%)	1
Deep vein thrombosis	1/233 (0.4%)	1	0/234 (0%)	0
Hypotension	0/233 (0%)	0	1/234 (0.4%)	1
Other (Not Including Serious) Adverse Events
	IDeg 3TW		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/233 (14.6%)		25/234 (10.7%)
Gastrointestinal disorders
Diarrhoea	11/233 (4.7%)	13	13/234 (5.6%)	16
Infections and infestations
Nasopharyngitis	13/233 (5.6%)	14	6/234 (2.6%)	6
Nervous system disorders
Headache	14/233 (6%)	18	8/234 (3.4%)	9

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.