Clinical Trial Results:
A Randomized, Double-blind, Placebo Controlled Trial to Assess Safety/Tolerability, Pharmacokinetics & Pharmacodynamics of Liraglutide in Paediatric (10 – 17 years old) Subjects with Type 2 Diabetes
Summary
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EudraCT number |
2010-021057-39 |
Trial protocol |
GB SI BE |
Global end of trial date |
30 Sep 2011
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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 |
21 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 |
NN2211-1800
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00943501 | ||
WHO universal trial number (UTN) |
U1111-1111-9256 | ||
Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allè, 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-000128-PIP01-07 | ||
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 |
19 Mar 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Sep 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2011
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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 assess the safety and tolerability of 0.3, 0.6, 0.9, 1.2 and 1.8 mg doses of liraglutide in the paediatric population (10 – 17 years of age).
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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 |
Subject previously using metformin, the pre-trial treatment regimen was continued unaltered throughout the study as background medication. Some subjects were on diet and exercise only. Pre-trial regimen was continued during the trial. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
02 Nov 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 |
Slovenia: 2
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
21
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EEA total number of subjects |
6
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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) |
3
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Adolescents (12-17 years) |
18
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Adults (18-64 years) |
0
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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 |
19 sites were activated in 4 countries; 14 sites enrolled study subjects (United States (9 sites –15 subjects), United Kingdom (3 sites –3 subjects), Slovenia (1 site – 2 subjects) and Belgium (1 site – 1 subject)) | ||||||||||||||||||
Pre-assignment
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Screening details |
Not applicable | ||||||||||||||||||
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 |
Double blind | ||||||||||||||||||
Roles blinded |
Investigator, Subject, Monitor, Data analyst | ||||||||||||||||||
Blinding implementation details |
This trial is double-blind and placebo controlled.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Liraglutide | ||||||||||||||||||
Arm description |
Subjects randomised to liraglutide treatment received 0.3 mg liraglutide daily (starting on Day 1) during the first week, followed by 0.6 mg daily (starting on Day 8) during the second week, 0.9 mg daily (starting on Day 15) during the third week, 1.2 mg daily (starting on Day 22) during the fourth week, and 1.8 mg daily (starting on Day 29) during the fifth and final treatment week. If a subject did not meet the dose escalation criteria, he/she continued on the highest dose reached. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Liraglutide
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Investigational medicinal product code |
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Other name |
Victoza (R)
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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 |
Liraglutide was administered once-daily by a s.c. FlexPen injection in the abdomen.
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
Liraglutide placebo, was administered once-daily by a s.c. FlexPen injection in the abdomen. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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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 |
Liraglutide placebo, was administered once-daily by a s.c. FlexPen injection in the abdomen.
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Baseline characteristics reporting groups
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Reporting group title |
Liraglutide
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Reporting group description |
Subjects randomised to liraglutide treatment received 0.3 mg liraglutide daily (starting on Day 1) during the first week, followed by 0.6 mg daily (starting on Day 8) during the second week, 0.9 mg daily (starting on Day 15) during the third week, 1.2 mg daily (starting on Day 22) during the fourth week, and 1.8 mg daily (starting on Day 29) during the fifth and final treatment week. If a subject did not meet the dose escalation criteria, he/she continued on the highest dose reached. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Liraglutide placebo, was administered once-daily by a s.c. FlexPen injection in the abdomen. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Liraglutide
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Reporting group description |
Subjects randomised to liraglutide treatment received 0.3 mg liraglutide daily (starting on Day 1) during the first week, followed by 0.6 mg daily (starting on Day 8) during the second week, 0.9 mg daily (starting on Day 15) during the third week, 1.2 mg daily (starting on Day 22) during the fourth week, and 1.8 mg daily (starting on Day 29) during the fifth and final treatment week. If a subject did not meet the dose escalation criteria, he/she continued on the highest dose reached. | ||
Reporting group title |
Placebo
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Reporting group description |
Liraglutide placebo, was administered once-daily by a s.c. FlexPen injection in the abdomen. |
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End point title |
Adverse Events [1] | |||||||||
End point description |
All AEs either observed by the investigator or reported spontaneously by the subjects were recorded by the investigator and evaluated. The AEs were collected from randomisation (Visit 2/week 1 day 1) to follow up (Visit 9/week 6 day 5+ 2 days)
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End point type |
Primary
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End point timeframe |
Randomisation (Visit 2/ week 1 day 1) to follow up (Visit 9/ week 6 day 5+ 2 days)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Hypoglycaemic episodes [2] | ||||||||||||||||||||||||
End point description |
1) Major-Subject unable to treat himself/herself. 2) Minor-An episode with symptoms consistent with hypoglycaemia with confirmation by plasma glucose <56mg/dL (3.1mmol/L) or full blood glucose<50mg/dL (2.8mmol/L) and which is self-handled by the subject. Any asymptomatic plasma glucose value <56mg/dl (3.1mmol/L) or full blood glucose value <50mg/dL (2.8mmol/L)
ADA Classification- 1) Severe-An episode requiring assistance of another person to actively administer carbohydrate, glucagons or other resuscitative actions. 2) Documented symptomatic- An episode during which typical symptoms of hypoglycaemia are accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L). 3)Asymptomatic -An episode not accompanied by typical symptoms of hypoglycaemia, but with a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).
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End point type |
Primary
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End point timeframe |
Randomisation (Visit 2/ week 1 day 1) to follow up (Visit 9/ week 6 day 5 + 2 days)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Anti-Liraglutide Antibodies [3] | |||||||||
End point description |
Anti-Liraglutide antibody assessment was a part of safety assessment in this trial.Blood samples for serum antibody against liraglutide were drawn at Visit 2 (randomisation/ week1 day 1) and Visit 9 (follow up/ week 6 day 5 + 2 days) . Blood samples for subjects discontinuing prematurely from the trial treatment (due to withdrawal) were drawn at the withdrawal visit. Antibody-positive samples were to be further characterised for neutralising effect and cross-reactivity.
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End point type |
Primary
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End point timeframe |
Visit 2 (Randomisation/ week 1 day 1) and Visit 9 (follow up/ week 6 day 5 + 2 days)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Biochemistry- Change from Baseline [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Biochemistry parameters were assessed at Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days).
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Physical Examination- Change from previous visit. [5] | ||||||||||||||||||
End point description |
Targeted physical examinations were performed at scheduled Visits and at any other time at the discretion of the Investigator.These results are based on assessments made at the final time point (Visit 8/Week 6 Day 3)
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End point type |
Primary
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End point timeframe |
Visit 2 (Randomisation/ week 1 day 1) to Visit 8 (Week 6 day 3)
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
ECG [6] | |||||||||||||||
End point description |
A standard 12-lead ECG evaluation was performed by the investigator at screening (Visit 1/ week -2 relative to randomisation) Visit 2 (randomisation /week 1 day 1) and Follow-up (Visit 9/ week 6 day 5 +2 days) and recorded as:
1. Normal
2. Abnormal; not clinically significant
3. Abnormal; clinically significant.
The values presented are overall interpretation for week 6 Day 5. (Follow up/Viist 9)
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week -2 relative to randomisation) Visit 2 (randomisation /week 1 day 1) and Follow-up (Visit 9/week 6 day 5 +2 days)
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Funduscopy [7] | |||||||||||||||||||||
End point description |
Funduscopy was a part of safety assessment of the trial. The occurences in both left and right eye at follow up are given below.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Pulse-Change from baseline [8] | |||||||||||||||
End point description |
Pulse was measured at all visits as necessary and as scheduled. Pulse was measured after subject has rested for 5 min.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) to follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Systolic Blood Pressure- Change from baseline [9] | |||||||||||||||
End point description |
Systolic blood pressures were measured at all visits as necessary and as scheduled. Blood pressure was measured after the subject has rested for 5 min.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week -2 relative to randomisation) to follow up (Visit 9/week 6 Day 5+ 2days)
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Diastolic Blood Pressure- Change from baseline [10] | |||||||||||||||
End point description |
Diastolic blood pressures was measured at all visits as necessary and as scheduled. Blood pressure was measured after resting for 5 min.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to rando misation) to follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Haematology-Change from baseline [11] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Haematology parameters were assessed at screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Urinalysis-pH Change from baseline [12] | ||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were perfomed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Fasting Plasma Glucose - Change from baseline | ||||||||||||
End point description |
FPG (from glucometer) was asessed from screening (Visit 1/week-2 relative to randomisation) to follow up (Visit 9/week 6 day 5+ 2 days). Results presented are for the change from baseline (week 1day1) to the last dose. (after 5 weeks of treatment)
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) to follow up (Visit 9/week 6 day 5+ 2 days)
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Statistical analysis title |
FPG-Change from baseline | ||||||||||||
Comparison groups |
Placebo v Liraglutide
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
other [13] | ||||||||||||
P-value |
= 0.1797 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Estimated treatmentdifference | ||||||||||||
Point estimate |
-1.44
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.61 | ||||||||||||
upper limit |
0.73 | ||||||||||||
Notes [13] - Exploratory |
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End point title |
HbA1c (%) - Change from baseline | ||||||||||||
End point description |
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c). Results presented are for the change from baseline (week1 day1) to the final time point (visit6/week 5 day7)
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End point type |
Primary
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End point timeframe |
Screening ( Visit 1/week -2 relative to randomisation) to Visit 6 (Week 5 day 7 )
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Statistical analysis title |
HbA1c- Change from baseline | ||||||||||||
Comparison groups |
Liraglutide v Placebo
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Number of subjects included in analysis |
19
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0007 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Estimated treatment difference | ||||||||||||
Point estimate |
-0.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.36 | ||||||||||||
upper limit |
-0.45 |
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End point title |
Urinalysis -Glucose [14] | |||||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were perfomed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Urinalysis -Ketones [15] | ||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were perfomed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Urinalysis-Leucocytes [16] | ||||||||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were performed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Urinalysis- Nitrite [17] | |||||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were perfomed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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No statistical analyses for this end point |
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End point title |
Urinalysis-Protein [18] | |||||||||||||||
End point description |
The analysis of pH, ketones, protein, blood,leukocyte esterase, nitrite and glucose were perfomed.
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End point type |
Primary
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End point timeframe |
Screening (Visit 1/week-2 relative to randomisation) and follow up (Visit 9/week 6 day 5+ 2 days)
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Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The summary statistics by treatment were the primary mode of statistical presentation of safety data. |
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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 |
Adverse events were collected from visit 1 to follow-up.Treatment emergent AEs are reported below.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
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Reporting groups
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Reporting group title |
Liraglutide
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Reporting group description |
Subjects randomised to liraglutide treatment received 0.3 mg liraglutide daily (starting on Day 1) during the first week, followed by 0.6 mg daily (starting on Day 8) during the second week, 0.9 mg daily (starting on Day 15) during the third week, 1.2 mg daily (starting on Day 22) during the fourth week, and 1.8 mg daily (starting on Day 29) during the fifth and final treatment week. If a subject did not meet the dose escalation criteria, he/she continued on the highest dose until the end of the trial. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Liraglutide placebo, was administered once-daily by a s.c. FlexPen injection in the abdomen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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21 Jul 2009 |
This substantial amendment primarily involves-
1. Addition of a new subject withdrawal criteria related to pancreatitis.
2.Update of one inclusion and two exclusion criteria.
3.Specification of the frequency of Safety Monitoring Board meetings.
4.Addition of new language to the Informed Consent as agreed with USFDA.
In addition to the above, a few minor inconsistencies and clarifications are necessary to make the protocol complete, accurate and more informative. Those have also been included. |
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20 Aug 2009 |
This substantial amendment involves the addition of text related to liraglutide toxicology results and results in the addition of approved text to the protocol in order to be aligned with the text previously added to the informed consent as requested by the FDA. |
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16 Jul 2010 |
This substantial amendment primarily involves :
1.Expansion (widening) of the HBA1C inclusion criteria (to ≥ 6.5% and ≤ 11.0%).
2.Expansion (widening) of the FPG randomisation criterion [ to 110-240 mg/dL, (6.1-13.3 mmol/L).
3.Altering the language of exclusion criterion involving subjects on prior use of antidiabetic treatment.
4. Altering the pharmacokinetic (blood) sampling schedule.
5. Replacement of measurement of CGRP in this study with CEA.
6.Addition of new and updated language and safety information to the protocol and Informed Consent as agreed with the regulatrory authorities. (or approved product labelling).
7.Allowance for protocol to incorporate an IV/IWRS system for drug distribution.
8. Minor changes, clarifications and corrections to several sections for making the protocol clear for execution. |
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09 Sep 2010 |
In this substantial protocol amendment-
1. It was clarified that a calcitonin level was obtained at Visit 1, Screening, (and not at Visit 2, Randomisation) in order to be avialable for eligibility evaluation, and at Visit 7 in Part I,for paediatric subjects.
2. It was clarified that a calcitonin level was obtained at Visit 1, Screening (and not a Visit 2 Randomisation),to be available for eligibility evaluation and at Visit 6 in part II for paediatric subjects.
3. A calcitonin level for adult subjects will be obtained at Visit 1, Screening (and not at Visit 2 Randomisation ) to be available for eligibility evaluation, and at Visit 6 in Part II.
4.The calcitonin level in Exclusion Criteria number 22 was changed from ≥ 100ng/L to ›50 ng/L.
5.A review of withdrawal criteria was added to Visits 7 and 8 in Part I and to Visits 6 and 7 in Part II.
6.A check of vital signs was added to the Flow Chart, Part I day 35, Visit 6.
7.It was clarified that body temperature will be recorded in°F or °C.
8.°F as representing degrees Fahrenheit or °C as representing degrees Celsius were added to the List of Abbreviations. |
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14 Dec 2010 |
This amendment was implemented in order to add Belgium as a participating country in this trial.
The language of the protocol and subject informed consent form was modified accordingly. A minor inconsistency was corrected, allowing for greater accuracy. |
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30 Sep 2011 |
The amendment was implemented in order to eliminate the part II of the trial, as per Novo Nordisk's agreement with PDCO on 3 May 2011 (Part II was to evaluate the dose range of 0.6 to 1.8mg liraglutide in paediatric subjects and also included a comparative adult group). In addition , minor inconsistencies were corrected in order to allow for greater accuracy.
Justification for the date entered- The amendment date -31Oct 2011 entered showed a validation error , hence the date has been entered as 30 Sep 2011, to surpass the validation error. The date entered here is global end of the trial date. The actual amendment date is 31 Oct 2011. |
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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. | |||
Small number of subjects analysed was the limitation for the trial. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/25036533 |