Primary objectiveTo confirm the superiority of liraglutide at the maximum tolerated dose (0.6 mg, 1.2 mg or 1.8 mg) versus placebo when added to metformin with or without basal insulin treatment in controlling glycaemia in children and adolescents (…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Change in HbA1c from baseline to week 26
Secondary outcome
At 26 and 52 weeks of treatment:
- HbA1c <7.0% (yes/no)
- HbA1c =<6.5% (yes/no)
- HbA1c <7.0% without severe or minor hypoglycaemic episodes (yes/no)
Change from baseline at 26 and 52 weeks of treatment in:
- Fasting plasma glucose (FPG)
- 7-point self-measured plasma glucose
- Body weight
-BMI standard deviation score (SDS)
Safety
- Adverse events (AEs) and serious adverse events (SAEs)
- Safety follow-up after 1 and 2 years: AEs and SAEs, growth velocity and
pubertal progression
Background summary
The first trial to assess safety and tolerability of liraglutide in children
and adolescents was the pharmacokinetic and pharmacodynamic trial
(NN2211-1800), conducted in paediatric subjects with type 2 diabetes, ages
10-17 years, in the EU and US.
The liraglutide pharmacokinetics in the paediatric population was similar to
that observed in adults.
The NN2211-3659 trial is being conducted to assess the efficacy and safety of
liraglutide in the paediatric population in order to potentially address the
unmet need for treatment of children and adolescents with type 2 diabetes and
also to fulfil the regulatory requirement for paediatric trials trom the
European Paediatric Committee (PDCO) of the European Medicines Agency (EMA) and
trom the U.S. Food and Drug Administration (FDA).
Study objective
Primary objective
To confirm the superiority of liraglutide at the maximum tolerated dose (0.6
mg, 1.2 mg or 1.8 mg) versus placebo when added to metformin with or without
basal insulin treatment in controlling glycaemia in children and adolescents
(ages 10-17 years) with type 2 diabetes.
Secondary objectives
To assess and compare the effect of liraglutide versus placebo in combination
with metformin withor without basal insulin treatment on:
- Parameters of glycaemic control
- Safety and tolerability
Study design
This is a multi-centre, 26-week randomised double-blind, parallel-group,
placebo-controlled clinical trial foliowed by a 26-week open-label extension in
subject's ages 10-17 years with type 2 diabetes.
After being titrated to 2000 mg of metformin or maximum tolerated dose (MTD)
(metformin dose must be *1000 mg
and *2000 mg) subjects will be randomised 1:1 to receive liraglutide (1.8 mg or
MTD) or liraglutide placebo. Subjects treated with basal insulin will continue
treatment with basal insulin.
Subjects already treated with 2000 mg or more of metformin and with a stabie
dose for at least 56 days prior to Visit 1 may advance directly to
randomisation (Visit 7) when eligibility according to the inclusion and
exclusion criteria has been confirmed. Subjects who are treated with basal
insulin should in addition to the stabie dose of metformin have a stabie dose
of basal insulin for at least 56 days in order to advance directly to Visit 7.
After 26 weeks of blinded treatment, the treatment allocation will be
unblinded. Subjects treated with liraglutide will continue their trial
medication until end of treatment. Subjects treated with liraglutide placebo
will discontinue their liraglutide placebo treatment. Rescue treatment will be
allowed for subjects in both treatment groups experiencing confirmed
hyperglycaemia. Subjects on rescue medication will stay in the trial.
Subjects treated with liraglutide for more than 3 months will complete 1 and 2
year follow-up visits.
Intervention
Subjects will be treated with liraglutide/liraglutide placebo and metformin as
described in detail in the trial design
section of this form.
Trial products supplied by sponsor:
Novo Nordisk will supply the following trial products:
- Liraglutide, 6.0 mg/mL, 3 mL pen-injector for s.c. injection
- Liraglutide placebo, 3 mL pen-injector for s.c. injection
- Metformin, 500 mg tabiets (non-investigational medicinal product)
Key assessments :
Efficacy:
- Glucose metabolism
- Body measurements
- Blood pressure
- Lipids
Safety:
- AEs and SAEs
- Hypoglycaemic episodes
- Biochemistry
- Haematology
- Growth parameters
- Pubertal assessment (Tanner staging)
- Hormones
- Biochemical parameters of bone metabolism
- Formation of anti-liraglutide antibodies
Study burden and risks
Relevant precautions have been implemented in the design and planned conduct of
this trial in order to minimise the risks and the inconveniences of trial
participation. All subjects participating in the trial will be monitored
closely through frequent site visits and telephone contacts.
Blood sampling and contacts with the clinic are considered an inconvenience for
the children participating in the trial.
On the other hand, the intensified treatment may help to improve glycaemic
controL
All subjects will, in order to ensure adequate treatment, be treated with
metformin throughout the trial.
lt is concluded that the potential benefits from participating in the trial
outweigh the potential risks.
The safety profile of liraglutide generated from the nonclinical and clinical
studies in adults has not revealed any safety issues that should prohibit
administration of liraglutide to children and adolescents. The results of this
trial will contribute to the development of new improved treatments for
children and adolescents with type 2 diabetes in the future.
Flemingweg 18
Alphen aan den Rijn 2408 AV
NL
Flemingweg 18
Alphen aan den Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
-Children and adolescents between the ages of 10-16 years. Subjects cannot turn 17 years and 11 months before the end of treatment (52 weeks);- Diagnosis of type 2 diabetes mellitus and treated for at least 30 days with:
- diet and exercise alone
- diet and exercise in combination with metformin monotherapy
- diet and exercise in combination with metformin and a stable* dose of basal insulin
- diet and exercise in combination with a stable* dose of basal insulin.
*Stable is defined as basal insulin adjustments up to 15%;- HbA1c
- *7.0% and *11% if diet and exercise treated
- *6.5% and *11% if treated with metformin as monotherapy, basal insulin as monotherapy or metformin and basal insulin in combination
- Body mass index (BMI) >85th percentile of the general age and gender matched population
Exclusion criteria
- Type 1 diabetes
- Maturity on set diabetes of the young (MODY)
- Use of any antidiabetic agent other than metformin and/or basal insulin within 90 days prior to screening
- Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator
- History of chronic pancreatitis or idiopathic acute pancreatitis
- Any clinically significant disorder, except for conditions associated with type 2 diabetes history which in the investigator's opinion could interfere with results of the trial
- Uncontrolled hypertension, treated or untreated >99th percentile for age and gender in children
- Known or suspected abuse of alcohol or narcotics
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-002605-29-NL |
| ClinicalTrials.gov | NCT01541215 |
| CCMO | NL57405.028.16 |