Clinical Trial Results:
DUALTM V – basal insulin switch: A trial comparing the efficacy and safety of insulin degludec/liraglutide versus insulin glargine in subjects with type 2 diabetes mellitus.
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
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Summary
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EudraCT number |
2012-004413-14 |
Trial protocol |
HU SK ES GR |
Global end of trial date |
04 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jul 2016
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First version publication date |
27 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN9068-3952
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01952145 | ||
WHO universal trial number (UTN) |
U1111-1135-1003 | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Global Clinical Registry (GCR,1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Global Clinical Registry (GCR,1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Mar 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Nov 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in subjects with type 2 diabetes mellitus (T2DM) on previous treatment with insulin glargine.
This is done by comparing the difference in change in glycosylated haemoglobin (HbA1c) from baseline after 26 weeks of treatment to a non-inferiority limit of 0.30% for insulin degludec/liraglutide versus insulin glargine.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki (59th World Medical Association [WMA] Assembly, October 2008) and International Conference on Harmonisation (ICH) Good Clinical Practice (May 1996) and 21 Code of Federal Regulations (CFR) 312.120.
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Background therapy |
Subjects were on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose) for at least 90 days prior to screening. Metformin treatment was to be continued at pre-trial dose level throughout the trial period, but reduction in dose of metformin treatment was allowed for safety reasons based on the investigator's judgement. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
20 Sep 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 80
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Country: Number of subjects enrolled |
Australia: 8
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Country: Number of subjects enrolled |
Mexico: 83
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Country: Number of subjects enrolled |
Russian Federation: 95
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Country: Number of subjects enrolled |
South Africa: 28
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Country: Number of subjects enrolled |
United States: 39
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Country: Number of subjects enrolled |
Slovakia: 75
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Country: Number of subjects enrolled |
Spain: 74
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Country: Number of subjects enrolled |
Greece: 35
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Country: Number of subjects enrolled |
Hungary: 40
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Worldwide total number of subjects |
557
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EEA total number of subjects |
224
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
412
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From 65 to 84 years |
145
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was conducted at 75 sites in 10 countries, as follows: Argentina: 5 sites; Australia: 4 sites; Greece: 6 sites, Hungary: 4 sites; Mexico: 5 sites, Russian Federation: 11 sites; Slovakia: 11 sites, South Africa: 4 sites; Spain: 6 sites, United States: 19 sites. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Screened subjects were diagnosed with T2DM and with a: 1) current treatment with insulin glargine (IGlar) >=90 days prior to screening. 2) stable daily dose of IGlar between 20 units and 50 units (both inclusive) >=56 days prior to screening. 3) stable daily dose of metformin (≥1500 mg or max tolerated dose) >=90 days prior to screening. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Not applicable.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Insulin Degludec/Liraglutide (IDegLira) | |||||||||||||||||||||||||||
Arm description |
Eligible subjects received IDegLira once daily (OD) for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin degludec liraglutide PDS290
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects randomised to treatment with IDegLira discontinued the pre-trial IGlar treatment prior to initiating IDegLira treatment with a start dose of 16 dose steps, equivalent to 16 units IDeg and 0.6 mg liraglutide. The maximum allowed dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). IDegLira was supplied in a 3 mL pre-filled PDS290 pen-injector with a fixed insulin degludec (IDeg)/liraglutide (lira) ratio of 100 units/3.6 mg per mL solution. IDegLira was to be injected subcutaneous (s.c., under the skin) in the thigh, upper arm (deltoid region) or abdomen (OD) approximately at the same time every day. The chosen injection area was to remain unchanged throughout the trial, but rotation within the area was recommended.
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Arm title
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Insulin Glargine (IGlar) | |||||||||||||||||||||||||||
Arm description |
Eligible subjects received IGlar OD for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin glargine
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Investigational medicinal product code |
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Other name |
Lantus®
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects randomised for treatment with IGlar discontinued the pre-trial IGlar and initiated Novo Nordisk provided IGlar treatment with a starting dose equal to the pre-trial daily dose (dose-to-dose switch). No predefined maximum dose was specified for IGlar treatment. IGlar 100 units/mL solution was supplied in a 3 mL pre-filled Lantus® SoloStar® pen-injector. IGlar was to be injected s.c., OD according to the approved label and using the pre-trial dosing time and injection site throughout the trial.
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Baseline characteristics reporting groups
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Reporting group title |
Insulin Degludec/Liraglutide (IDegLira)
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Reporting group description |
Eligible subjects received IDegLira once daily (OD) for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Insulin Glargine (IGlar)
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Reporting group description |
Eligible subjects received IGlar OD for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Insulin Degludec/Liraglutide (IDegLira)
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Reporting group description |
Eligible subjects received IDegLira once daily (OD) for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | ||
Reporting group title |
Insulin Glargine (IGlar)
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Reporting group description |
Eligible subjects received IGlar OD for a duration of 26-week. The total duration of the trial was approximately 29-week, consisting of a 2-week screening period, a 26-week treatment period and a follow-up visit 1-week after end of treatment. | ||
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End point title |
Change from baseline in HbA1c | ||||||||||||
End point description |
The primary endpoint was change from baseline in HbA1c after 26 weeks of treatment. Analysis population: The Full Analysis Set included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
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End point type |
Primary
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End point timeframe |
After 26 weeks of treatment.
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Statistical analysis title |
IDegLira versus IGlar | ||||||||||||
Statistical analysis description |
The change from baseline after 26 weeks of treatment was analysed using analysis of covariance (ANCOVA) model with treatment and region as fixed effects and baseline HbA1c as a covariate. Missing data were imputed using LOCF.
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Comparison groups |
Insulin Degludec/Liraglutide (IDegLira) v Insulin Glargine (IGlar)
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Number of subjects included in analysis |
557
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Treatment contrast | ||||||||||||
Point estimate |
-0.59
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.74 | ||||||||||||
upper limit |
-0.45 | ||||||||||||
| Notes [1] - Non-inferiority of IDegLira versus IGlar was considered as confirmed, if the 95% confidence interval (CI) for the mean treatment difference was entirely below 0.30%. |
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End point title |
Change from baseline in body weight | ||||||||||||
End point description |
Change from baseline in body weight after 26 weeks of treatment. Analysis population: Full Analysis Set. Missing values (including intermittent missing values) were imputed using the LOCF method.
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End point type |
Secondary
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End point timeframe |
After 26 weeks of treatment.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of treatment emergent confirmed hypoglycaemic episodes | |||||||||
End point description |
Confirmed hypoglycaemic episodes were defined as either: Severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or an episode biochemically confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.
Analysis population: The safety analysis set included all subjects receiving at least one dose of trial product. Subjects contributed to the evaluation “as treated”.
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End point type |
Secondary
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End point timeframe |
During 26 weeks of treatment.
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Week 0 to week 27 (26-week treatment period and a follow-up visit 1 week after end of treatment).
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Adverse event reporting additional description |
All AEs described below are treatment-emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Analysis population: safety analysis set.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
Insulin glargine (IGlar)
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Reporting group description |
Eligible subjects received IGlar OD for a duration of 26-week. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Insulin degludec/liraglutide (IDegLira)
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Reporting group description |
Eligible subjects received IDegLira OD for a duration of 26-week. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 Oct 2013 |
Introduction of intensification trial (NN9068-4119), update of subject information/informed consent forms and pregnancy section. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/26934259 |
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