DiabetesPhase 3NCT00623194

Safety Follow-up on Children and Adolescents With Type 1 Diabetes Treated With Insulin Detemir. An Extension to Trial NN304-1689

A Phase 3 study testing insulin detemir and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S at 32 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This trial is conducted in Europe. The aim of this research is to assess the safety of continuous treatment with insulin detemir following participation in trial NN304-1689 (NCT00435019) on antibody development. Read more about this study

Who is it for?: Ages 3 to 17 years
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 1
What is being tested?: insulin detemir and insulin aspart
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 146 participants
Where: 32 sitesin 11 countries
Study dates: Feb 2008to Sep 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Informed Consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The parents or legal representative of the subject must sign and date the Informed Consent Form.
Finalised 52 weeks of treatment with insulin detemir in trial NN304-1689.
Fertile females (girls who have had their first menstrual period) must use adequate contraception (barrier methods, contraceptive pills or intrauterine device (IUD)) if there is any risk of pregnancy in the opinion of the Investigator. For Denmark and France only contraceptive pills or intrauterine device are considered as adequate contraceptive methods.

Who cannot join

Significant concomitant disease such as endocrine, hepatic, renal, cardiac, respiratory, neurological, gastrointestinal, malignant or pancreatic diseases as judged by the Investigator.
Pregnant or the intention of becoming pregnant.
Previous participation in this trial (defined as enrolment).

Trial locations and contacts

32 sites in 11 countries.

Country

City, postcode or hospital

32 sites in 11 countries

Finland4 sites

Novo Nordisk Investigational Site
Helsinki, 00029
Novo Nordisk Investigational Site
Oulu, 90029
Novo Nordisk Investigational Site
Seinäjoki, 60220
Novo Nordisk Investigational Site
Turku, 20100

Other trials in Finland

Russia4 sites

Novo Nordisk Investigational Site
Moscow, 117036
Novo Nordisk Investigational Site
Moscow, 119049
Novo Nordisk Investigational Site
Moscow, 125373
Novo Nordisk Investigational Site
Saint Petersburg, 193144

Other trials in Russia

Turkey (Türkiye)4 sites

Novo Nordisk Investigational Site
Altunizade-Istanbul, 34662
Novo Nordisk Investigational Site
Antalya, 07059
Novo Nordisk Investigational Site
Istanbul, 34093
Novo Nordisk Investigational Site
Izmir, 35340

Other trials in Turkey (Türkiye)

Bulgaria3 sites

Novo Nordisk Investigational Site
Pleven, 5800
Novo Nordisk Investigational Site
Sofia, 1606
Novo Nordisk Investigational Site
Varna, 9010

Other trials in Bulgaria

Czechia3 sites

Novo Nordisk Investigational Site
Olomouc, 77520
Novo Nordisk Investigational Site
Pardubice, 53203
Novo Nordisk Investigational Site
Prague, 15018

Other trials in Czechia

Denmark3 sites

Novo Nordisk Investigational Site
Glostrup Municipality, 2600
Novo Nordisk Investigational Site
Kolding, 6000
Novo Nordisk Investigational Site
Odense, 5000

Other trials in Denmark

Poland3 sites

Novo Nordisk Investigational Site
Gdansk, 80-211
Novo Nordisk Investigational Site
Kielce, 25-734
Novo Nordisk Investigational Site
Warsaw, 01-184

Other trials in Poland

United Kingdom3 sites

Novo Nordisk Investigational Site
Aberdeen, AB25 2ZG
Novo Nordisk Investigational Site
Dundee, DD1 9SY
Novo Nordisk Investigational Site
Norfolk, NR4 7UY

Other trials in United Kingdom

France2 sites

Novo Nordisk Investigational Site
Paris, 75015
Novo Nordisk Investigational Site
Toulouse, 31059

Other trials in France

Hungary2 sites

Novo Nordisk Investigational Site
Budapest, 1083
Novo Nordisk Investigational Site
Miskolc, 3501

Other trials in Hungary

North Macedonia1 site

Novo Nordisk Investigational Site
Skopje, 1000

Other trials in North Macedonia

About this study

Official title: A 52-Week, Multinational, Multi-Centre, Open-Labelled Extension Trial of Insulin Detemir in Children and Adolescents 3-17 Years With Type 1 Diabetes on a Basal-Bolus Regimen With Insulin Aspart as Bolus Insulin

Conditions: Diabetes, Diabetes Mellitus, Type 1
Being tested: insulin detemir, insulin aspart
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

insulin detemirDrug
Treat-to-target dose titration scheme (individually adjusted), injection s.c. (under the skin), once or twice daily.
insulin aspartDrug
Treat-to target dose titration scheme (individually adjusted), injection s.c. (under the skin), at larger meals.

Study groups in NCT00623194
Study group	Role	What they receive
insulin detemir	Experimental	Insulin detemir up to twice daily plus insulin aspart at larger meals, doses are adjusted individually (treatment up to 104 weeks) Receives: Drug: insulin detemir; Drug: insulin aspart

What is being measured

The primary outcome is the main question the study is designed to answer.

Insulin Detemir-insulin Aspart Cross-reacting Antibodies
Estimated amount of bound antibodies in percent of total antibodies. The primary analysis of cross-reacting antibodies included results from blood samples taken before insulin detemir and less than 3 hours after insulin aspart injection. In addition, an analysis was done including results from samples taken before insulin detemir and less than 2.5 hours after insulin aspart injection.
Measured: week 0, 52 and 104

Secondary outcomes (16)

Development of Insulin Detemir Specific Antibodies and Insulin Aspart Specific Antibodies
Amount of Insulin Detemir and Insulin Aspart specific antibodies in percent of total antibodies after 0, 52 and 104 weeks.
Measured: At 0, 52 and 104 weeks
Glycosylated Haemoglobin A1c (HbA1c)
Glycosylated Haemoglobin A1c (HbA1c) measured after 104 weeks.
Measured: At 104 weeks
Fasting Plasma Glucose Values
FPG (Fasting Plasma Glucose) values after 104 weeks.
Measured: At 104 weeks
Hypoglycaemic Episodes
Mild: signs/symptoms but able to treat him/herself. Moderate: signs/symptoms not able to treat him/herself. Responds to oral treatment.
Severe: signs/symptoms and unable to treat him/herself. semiconscious/unconscious/in coma +/- convulsion and may require parenteral treatment.
Measured: Weeks 0-104
BMI (Body Mass Index)
BMI (Body Mass Index) after 104 weeks.
Measured: At 104 weeks
SD-score (Z-score) for Body Weight
Standard deviation-score (SD-score) after 104 weeks. The SD-score for weight was calculated based on a British reference population from 1990. To estimate the growth of children, standardised mean weight values were calculated for each month of age and for each sex. Thus, a child with a weight equal to the mean value for its age and sex has an SD score of 0, while a child with a weight 2 SDs above the mean value for its age and sex has an SD score of +2.
Measured: At 104 weeks
Diabetic Ketoacidosis
Diabetic ketoacidosis requiring hospitalisation
Measured: At 104 weeks
Insulin Dose
Daily insulin doses (basal (Insulin Detemir) and bolus (Insulin Aspart)) at week 104.
Measured: At 104 weeks
Laboratory Values: Albumin Serum and Total Protein Serum (g/dL)
Albumin Serum and Total Protein Serum after 104 weeks.
Measured: At 104 weeks
Laboratory Values: Creatine Serum Umol/L
Creatine serum after 104 weeks.
Measured: At 104 weeks
Laboratory Values: Sodium Serum, Potassium Serum and Haemoglobin (mmol/L)
Sodium Serum, Potassium Serum and Haemoglobin after 104 weeks.
Measured: At 104 weeks
Laboratory Values: Alkaline Phosphatase Serum, Alanine Aminotransferase Serum and Lactate Dehydrogenase Serum (U/L)
Alkaline phosphatase serum, Alanine Aminotransferase serum and Lactate Dehydrogenase serum after 104 weeks.
Measured: At 104 weeks
Laboratory Values: Leukocytes and Thrombocytes
Leukocytes and Thrombocytes after 104 weeks.
Measured: At 104 weeks
Fundoscopy/Fundus Photography
Fundoscopy after 104 weeks. Abn. CS = Abnormal, clinically significant Abn. NCS = Abnormal, Not clinically significant
Abn. CS = Abnormal, clinically significant Abn. NCS = Abnormal, Not clinically significant
Measured: at 52 weeks and at 104 weeks
Vital Signs: Blood Pressure
Blood pressure (Systolic and Diastolic) after 104 weeks.
Measured: At 104 weeks
Vital Signs: Pulse
Pulse at week 104
Measured: At 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Sep 2009

First posted25 Feb 2008 (estimated)
Study startFeb 2008
Primary completionSep 2009
Study completionSep 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 146 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00623194
Sponsor's protocol ID: NN304-1690
Other IDs: 2006-002478-23
Status last verified: Oct 2016
First submitted: 14 Feb 2008
Last updated: 28 Nov 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Thalange N, Bereket A, Jensen LB, Hiort LC, Peterkova V. Development of Insulin Detemir/Insulin Aspart Cross-Reacting Antibodies Following Treatment with Insulin Detemir: 104-week Study in Children and Adolescents with Type 1 Diabetes Aged 2-16 Years. Diabetes Ther. 2016 Dec;7(4):713-724. doi: 10.1007/s13300-016-0196-5. Epub 2016 Sep 6.
PubMed 27600385

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 52-Week, Multinational, Multi-Centre, Open-Labelled Extension Trial of Insulin Detemir in Children and Adolescents 3-17 Years With Type 1 Diabetes on a Basal-Bolus Regimen With Insulin Aspart as Bolus Insulin
ClinicalTrials.gov ID: NCT00623194
Acronym / sponsor ID: NN304-1690
Conditions: Diabetes, Diabetes Mellitus, Type 1
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 146 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: Sep 2009 (actual)
Study completion: Sep 2009 (actual)
First posted: 25 Feb 2008 (estimated)
Results: Posted 24 Jan 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
insulin detemir	Experimental	Drug: insulin detemir, Drug: insulin aspartInsulin detemir up to twice daily plus insulin aspart at larger meals, doses are adjusted individually (treatment up to 104 weeks)

Who may qualify

Ages: 3 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Informed Consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The parents or legal representative of the subject must sign and date the Informed Consent Form.
Finalised 52 weeks of treatment with insulin detemir in trial NN304-1689.
Fertile females (girls who have had their first menstrual period) must use adequate contraception (barrier methods, contraceptive pills or intrauterine device (IUD)) if there is any risk of pregnancy in the opinion of the Investigator. For Denmark and France only contraceptive pills or intrauterine device are considered as adequate contraceptive methods.

Key exclusion criteria (3 listed)

Significant concomitant disease such as endocrine, hepatic, renal, cardiac, respiratory, neurological, gastrointestinal, malignant or pancreatic diseases as judged by the Investigator.
Pregnant or the intention of becoming pregnant.
Previous participation in this trial (defined as enrolment).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
insulin detemirTreat-to-target dose titration scheme (individually adjusted), injection s.c. (under the skin), once or twice daily.	Drug	insulin detemir
insulin aspartTreat-to target dose titration scheme (individually adjusted), injection s.c. (under the skin), at larger meals.	Drug	insulin detemir

Primary outcome

Insulin Detemir-insulin Aspart Cross-reacting Antibodies
Time frame: week 0, 52 and 104
Estimated amount of bound antibodies in percent of total antibodies. The primary analysis of cross-reacting antibodies included results from blood samples taken before insulin detemir and less than 3 hours after insulin aspart injection. In addition, an analysis was done including results from samples taken before insulin detemir and less than 2.5 hours after insulin aspart injection.

16 secondary outcomes

Development of Insulin Detemir Specific Antibodies and Insulin Aspart Specific Antibodies
Time frame: At 0, 52 and 104 weeks
Glycosylated Haemoglobin A1c (HbA1c)
Time frame: At 104 weeks
Fasting Plasma Glucose Values
Time frame: At 104 weeks
Hypoglycaemic Episodes
Time frame: Weeks 0-104
BMI (Body Mass Index)
Time frame: At 104 weeks
SD-score (Z-score) for Body Weight
Time frame: At 104 weeks
Diabetic Ketoacidosis
Time frame: At 104 weeks
Insulin Dose
Time frame: At 104 weeks
Laboratory Values: Albumin Serum and Total Protein Serum (g/dL)
Time frame: At 104 weeks
Laboratory Values: Creatine Serum Umol/L
Time frame: At 104 weeks
Laboratory Values: Sodium Serum, Potassium Serum and Haemoglobin (mmol/L)
Time frame: At 104 weeks
Laboratory Values: Alkaline Phosphatase Serum, Alanine Aminotransferase Serum and Lactate Dehydrogenase Serum (U/L)
Time frame: At 104 weeks
Laboratory Values: Leukocytes and Thrombocytes
Time frame: At 104 weeks
Fundoscopy/Fundus Photography
Time frame: at 52 weeks and at 104 weeks
Vital Signs: Blood Pressure
Time frame: At 104 weeks
Vital Signs: Pulse
Time frame: At 104 weeks

Results and safety

Results posted to the registry on 24 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Insulin Detemir	146	141

Primary outcome: Insulin Detemir-insulin Aspart Cross-reacting Antibodies

Time frame: week 0, 52 and 104. Mean (Standard Error). Unit: Percent bound of total

Measure	Insulin Detemir n = 146
Week 0 (3 hours)	31.11 (1.25)
Week 52 (3 hours)	43.99 (1.02)
Week 104 (3 hours)	35.96 (1.14)
Week 0 (2.5 hours)	31.22 (1.23)
Week 52 (2.5 hours)	44.09 (1.01)
Week 104 (2.5 hours)	35.92 (1.13)

Population analysed: Full analysis set 146 (100%), safety analysis set 146 (100%) The full analysis set was used for efficacy analyses and included subjects with signed informed consent who had been exposed to trial drug in extension. The safety analysis set included all subjects with a signed informed consent who were exposed in the extension.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse events were collected over a period of 104 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Insulin Detemir	12 of 146 (8.2%)	108 of 146 (74%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27600385Thalange N, Bereket A, Jensen LB, Hiort LC, Peterkova V. Development of Insulin Detemir/Insulin Aspart Cross-Reacting Antibodies Following Treatment with Insulin Detemir: 104-week Study in Children and Adolescents with Type 1 Diabetes Aged 2-16 Years. Diabetes Ther. 2016 Dec;7(4):713-724. doi: 10.1007/s13300-016-0196-5. Epub 2016 Sep 6.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

32 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing insulin detemir and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S at 32 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Finland, Russia, Turkey (Türkiye), Bulgaria, Czechia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin Detemir-insulin Aspart Cross-reacting Antibodies (time frame: week 0, 52 and 104). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00623194, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.