Clinical Trial Results:
This trial is a randomized, single-centre, double-blind, two-period cross-over glucose clamp trial to test for bioequivalence between two SIBA (IDeg) formulations in healthy subjects.
This trial is part of two PIPs with EMA decision numbers P/44/2010 and P/96/2011
Summary
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EudraCT number |
2011-002949-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
02 Oct 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2016
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First version publication date |
28 Jul 2015
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Other versions |
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 |
NN1250-1988
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00966368 | ||
WHO universal trial number (UTN) |
U1111-1122-2992 | ||
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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000456-PIP01-08 EMEA-000479-PIP01-08 | ||
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 |
10 Jun 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Oct 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Oct 2009
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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 |
The primary objective is to test for bioequivalence between two formulations of Insulin Degludec (I454) based on AUCI454,0-120h,SD and Cmax,I454,SD.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki 59th WMA General Assembly, Seoul,October 2008, and ICH Good Clinical Practice 01-May-1996.
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Background therapy |
Not Applicable | ||
Evidence for comparator |
Not Applicable | ||
Actual start date of recruitment |
04 Aug 2009
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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 |
United States: 26
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Worldwide total number of subjects |
26
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EEA total number of subjects |
0
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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) |
26
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
One site in United States. | |||||||||||||||
Pre-assignment
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Screening details |
Not Applicable | |||||||||||||||
Period 1
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Period 1 title |
Period 1
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||
Blinding implementation details |
Double - blind, randomised, 2 period cross-over study. Novo Nordisk study staff were also blinded in this study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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IDeg (E) in period 1 | |||||||||||||||
Arm description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials, in period 1 | |||||||||||||||
Arm type |
Cross over | |||||||||||||||
Investigational medicinal product name |
IDeg(E)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3 -Treatment period Day 1-6), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Arm title
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IDeg (M) in period 1 | |||||||||||||||
Arm description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials, in period 1 | |||||||||||||||
Arm type |
Cross over | |||||||||||||||
Investigational medicinal product name |
IDeg (M)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3-Treatment period Day 1-6), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Period 2
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Period 2 title |
Period 2
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||
Blinding implementation details |
Double blind, 2 period crossover study. Novo Nordisk study staff were also blinded in this study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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IDeg (E) in period 2 | |||||||||||||||
Arm description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials, in period 2 | |||||||||||||||
Arm type |
Cross over | |||||||||||||||
Investigational medicinal product name |
IDeg(E)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3-Treatment period Day 1-6), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Arm title
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IDeg (M) in period 2 | |||||||||||||||
Arm description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials, in period 2. | |||||||||||||||
Arm type |
Cross over | |||||||||||||||
Investigational medicinal product name |
IDeg (M)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3-Treatment period Day 1-6 ), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Period 3
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Period 3 title |
Period 3 (Completers)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||
Blinding implementation details |
Double blind, 2 period crossover study. Novo Nordisk study staff were also blinded in this study.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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IDeg (E) | |||||||||||||||
Arm description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
IDeg(E)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3-Treatment period Day 1-6), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Arm title
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IDeg (M) | |||||||||||||||
Arm description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
IDeg (M)
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Investigational medicinal product code |
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Other name |
Insulin Degludec, insulin 454, I454, SIBA
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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 |
Each subject was allocated to a single injection of trial product on 2 occasions (Visits 2 and 3-Treatment period Day 1-6), and was therefore to receive 1 injection of each IDeg formulation during the trial. The dose level of IDeg was 0.4 U/kg body weight. Trial products were administered as a subcutaneous injection into a lifted skin fold of the anterior surface of the thigh using an appropriate 1 mL syringe.
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Baseline characteristics reporting groups
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Reporting group title |
Period 1
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IDeg (E) in period 1
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Reporting group description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials, in period 1 | ||
Reporting group title |
IDeg (M) in period 1
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Reporting group description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials, in period 1 | ||
Reporting group title |
IDeg (E) in period 2
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Reporting group description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials, in period 2 | ||
Reporting group title |
IDeg (M) in period 2
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Reporting group description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials, in period 2. | ||
Reporting group title |
IDeg (E)
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Reporting group description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials. | ||
Reporting group title |
IDeg (M)
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Reporting group description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials |
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End point title |
AUCI454,0-120h,SD -Area under the serum IDeg concentration time curve. | ||||||||||||
End point description |
Area under the serum insulin 454 (IDeg) concentration-time curve
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End point type |
Primary
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End point timeframe |
0-120 hours after single dose.
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Statistical analysis title |
AUC IDeg (0-120 h) | ||||||||||||
Comparison groups |
IDeg (M) v IDeg (E)
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Number of subjects included in analysis |
51
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Treatment ratio | ||||||||||||
Point estimate |
1
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
0.94 | ||||||||||||
upper limit |
1.05 | ||||||||||||
Notes [1] - For AUCI454,0-120h,SD bioequivalence between the 2 IDeg formulations will be claimed if the 90% CI of the treatment ratio for both AUC (0-120h) and Cmax is fully within the interval [80%;125%]. Please note that the analysis type is bioequivalence. The "Number of subjects included in analysis" is 26, not 51 as stated in the above table (due to EudraCT IT system error). |
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End point title |
Cmax I454,SD-Maximum observed serum IDeg concentration after single-dose | ||||||||||||
End point description |
Maximum observed serum IDeg concentration after single-dose.
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End point type |
Primary
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End point timeframe |
within 0 to 120 hours after dosing
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Statistical analysis title |
Cmax IDeg, SD | ||||||||||||
Comparison groups |
IDeg (M) v IDeg (E)
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Number of subjects included in analysis |
51
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [2] | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Treatment ratio | ||||||||||||
Point estimate |
0.97
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
0.89 | ||||||||||||
upper limit |
1.05 | ||||||||||||
Notes [2] - For Cmax,I454,SD, bioequivalence between the 2 IDeg formulations will be claimed if the 90% CI of the treatment ratio for both AUC (0-120h) and Cmax is fully within the interval [80%;125%]. Please note the analysis type is bioequivalence. The "Number of subjects included in analysis" is 26, not 51 as stated in the above table (due to EudraCT IT system error). |
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End point title |
tmax I454,SD,Time to maximum observed serum IDeg concentration after dosing | ||||||||||||
End point description |
Time to maximum observed serum IDeg concentration after dosing.
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End point type |
Secondary
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End point timeframe |
within 0 to 120 hours after dosing
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No statistical analyses for this end point |
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End point title |
AUCI454,0-24h,SD-Area under the serum IDeg concentration-time curve after single dose. | ||||||||||||
End point description |
Area under the serum IDeg concentration-time curve after single dose.
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End point type |
Secondary
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End point timeframe |
0-24 hours after single dose
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No statistical analyses for this end point |
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End point title |
t½,I454-Terminal half-life for IDeg (within 0-120 hours after dosing) | ||||||||||||
End point description |
Terminal half-life for IDeg within 0-120 hours after dosing
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End point type |
Secondary
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End point timeframe |
0-120 hours after dosing
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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 |
Treatment to follow-up
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Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
IDeg (E)
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Reporting group description |
Subjects received IDeg (E), an insulin degludec formulation used in the phase 2 trials. | |||||||||||||||||||||
Reporting group title |
IDeg (M)
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Reporting group description |
Subjects received IDeg (M), an insulin degludec formulation used in the phase 3 trials. | |||||||||||||||||||||
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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? No | |||
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. | |||
Not Applicable |