DiabetesPhase 4SimpleMix™NCT01427920

Comparison of Biphasic Insulin Aspart 30 Individually Adjusted by the Subject and the Trial Physician, Both Combined With Metformin in Subjects With Type 2 Diabetes

A Phase 4 study testing biphasic insulin aspart 30 in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 41 sites in 6 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 was conducted in Asia, Europe and South America. The aim of this trial was to confirm efficacy of subject driven titration (individually adjusted) of biphasic insulin aspart 30 (BIAsp 30) twice daily in terms of glycaemic control assessed by change in glycosylated haemoglobin (HbA1c). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: biphasic insulin aspart 30
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 348 participants
Where: 41 sitesin 6 countries
Study dates: Sep 2011to Jul 2012
Phase: Phase 4
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosed with type 2 diabetes for a minimum of 12 months prior to Visit 1 (screening)
Currently treated with a basal insulin analogue for at least 3 months prior to Visit 1 (screening)
Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to Visit 1 (screening)
HbA1c higher or equal to 7.0% and below or equal to 10.0% (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Body Mass Index (BMI) below or equal to 40.0 kg/m^2
Able and willing to eat at least 2 main meals each day during the trial
Able and willing to adhere to the protocol including compliance with performance of self measured plasma glucose (SMPG), injection regimen and titrating themselves according to the protocol
Experience in performing self measured plasma glucose (SMPG)

Who cannot join

Treatment with any thiazolidinedione (TZD) and glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to Visit 1 (screening)
Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Impaired kidney function with serum creatinine above or equal to 133 micromol/L (1.5 mg/dL) for males and above or equal to 124 micromol/L (1.4 mg/dL) for females (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure higher or equal to 180 mmHg and/or diastolic blood pressure higher or equal to 100 mmHg)
Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations) or bolus insulin. Previous use of pre-mixed or bolus insulin products was allowed only in case of hospitalisation or a severe condition requiring intermittent use of pre-mixed or bolus insulin products for less than 14 consecutive days, but not during the last 3 months prior to screening visit (Visit 1)

Trial locations and contacts

41 sites in 6 countries.

Country

City, postcode or hospital

41 sites in 6 countries

India8 sites

Novo Nordisk Investigational Site
Ahmedabad, Gujarat, 380 015
Novo Nordisk Investigational Site
Belagavi, Karnataka, 590001
Novo Nordisk Investigational Site
Chennai, Tamil Nadu, 600028
Novo Nordisk Investigational Site
Coimbatore, Tamil Nadu, 641018
Novo Nordisk Investigational Site
Kolkata, West Bengal, 700054
Novo Nordisk Investigational Site
Mumbai, Maharashtra, 400007
Novo Nordisk Investigational Site
New Delhi, New Delhi, 110085
Novo Nordisk Investigational Site
Thriruvananthapuram, 695 032

Other trials in India

Poland8 sites

Novo Nordisk Investigational Site
Bialystok, 15-404
Novo Nordisk Investigational Site
Gdansk, 80-858
Novo Nordisk Investigational Site
Lodz, 90-242
Novo Nordisk Investigational Site
Lubin, 59-300
Novo Nordisk Investigational Site
Ruda Śląska, 41-709
Novo Nordisk Investigational Site
Sopot, 81-756
Novo Nordisk Investigational Site
Warsaw, 00-911
Novo Nordisk Investigational Site
Wroclaw, 50-127

Other trials in Poland

Spain7 sites

Novo Nordisk Investigational Site
Almería, 04001
Novo Nordisk Investigational Site
Centelles (Barcelona), 08540
Novo Nordisk Investigational Site
La Roca Del Vallés (Barcelona), 08430
Novo Nordisk Investigational Site
Málaga, 29006
Novo Nordisk Investigational Site
Palma de Mallorca, 07014
Novo Nordisk Investigational Site
Valencia, 46014
Novo Nordisk Investigational Site
Vic (Barcelona), 08500

Other trials in Spain

United Kingdom7 sites

Novo Nordisk Investigational Site
Doncaster, DN9 2HY
Novo Nordisk Investigational Site
Ipswich, IP4 5PD
Novo Nordisk Investigational Site
Manchester, M41 5SL
Novo Nordisk Investigational Site
Northwood, HA6 2RN
Novo Nordisk Investigational Site
Reading, RG7 3SQ
Novo Nordisk Investigational Site
Scunthorpe, DN15 6HX
Novo Nordisk Investigational Site
Wirral, Merseyside, CH63 4JY

Other trials in United Kingdom

China6 sites

Novo Nordisk Investigational Site
Beijing, Beijing Municipality, 100034
Novo Nordisk Investigational Site
Chongqing, Chongqing Municipality, 404000
Novo Nordisk Investigational Site
Dalian, Liaoning, 116033
Novo Nordisk Investigational Site
Lanzhou, Gansu, 730000
Novo Nordisk Investigational Site
Tianjin, 300211
Novo Nordisk Investigational Site
Zhengzhou, Henan, 450052

Other trials in China

Argentina5 sites

Novo Nordisk Investigational Site
Capital Federal, 1405
Novo Nordisk Investigational Site
Capital Federal, C1056ABJ
Novo Nordisk Investigational Site
Chacabuco, B6740ELF
Novo Nordisk Investigational Site
Córdoba, 5000
Novo Nordisk Investigational Site
Córdoba, X5006IKK

Other trials in Argentina

About this study

Official title: A 20 Week Randomised, Multinational, Open Labelled, 2 Armed, Parallel Group Comparison of Twice Daily Subject Driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Versus Twice Daily Investigator-driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Both in Combination With Metformin in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin Analogues

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: biphasic insulin aspart 30
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

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

biphasic insulin aspart 30Drug
Administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued.

Study groups in NCT01427920
Study group	Role	What they receive
Subject-driven titration BIAsp 30 (BID) + metformin	Experimental	The subjects performed the titration of BIAsp 30 dose. Receives: Drug: biphasic insulin aspart 30
Investigator-driven titration BIAsp 30 (BID) + metformin	Active comparator	The investigator performed the titration of BIAsp 30 dose. Receives: Drug: biphasic insulin aspart 30

What is being measured

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

Change in HbA1c (Glycosylated Haemoglobin) - FAS
Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in full analysis set (FAS).
Measured: Week 0, week 20
Change in HbA1c (Glycosylated Haemoglobin) - PP
Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in per protocol (PP) analysis set.
Measured: Week 0, week 20

Secondary outcomes (5)

Change in Fasting Plasma Glucose (FPG) (Central Laboratory Values)
Estimated mean change from baseline in FPG after 20 Weeks of treatment
Measured: Week 0, week 20
Number of Treatment Emergent Hypoglycaemic Episodes
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of trial product, and no later than one day after product administration. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Measured: Week 0 to week 20
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.
Measured: Week 0
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.
Measured: Week 4
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.
Measured: Week 20

Timeline

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

Sep 2011Jul 2012

First posted2 Sep 2011 (estimated)
Study startSep 2011
Primary completionJul 2012
Study completionJul 2012

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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 348 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01427920
Sponsor's protocol ID: BIASP-3878
Other IDs: 2010-024303-27, U1111-1118-4096
Acronym: SimpleMix™
Status last verified: Jan 2017
First submitted: 31 Aug 2011
Last updated: 24 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Gao Y, Luquez C, Lynggaard H, Andersen H, Saboo B. The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration. Curr Med Res Opin. 2014 Dec;30(12):2483-92. doi: 10.1185/03007995.2014.960512. Epub 2014 Sep 29.
PubMed 25180608

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 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 20 Week Randomised, Multinational, Open Labelled, 2 Armed, Parallel Group Comparison of Twice Daily Subject Driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Versus Twice Daily Investigator-driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Both in Combination With Metformin in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin Analogues
ClinicalTrials.gov ID: NCT01427920
Acronym / sponsor ID: SimpleMix™ / BIASP-3878
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 348 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Sep 2011
Primary completion: Jul 2012 (actual)
Study completion: Jul 2012 (actual)
First posted: 2 Sep 2011 (estimated)
Results: Posted 12 Sep 2013

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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Subject-driven titration BIAsp 30 (BID) + metformin	Experimental	Drug: biphasic insulin aspart 30The subjects performed the titration of BIAsp 30 dose.
Investigator-driven titration BIAsp 30 (BID) + metformin	Active comparator	Drug: biphasic insulin aspart 30The investigator performed the titration of BIAsp 30 dose.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Diagnosed with type 2 diabetes for a minimum of 12 months prior to Visit 1 (screening)
Currently treated with a basal insulin analogue for at least 3 months prior to Visit 1 (screening)
Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to Visit 1 (screening)
HbA1c higher or equal to 7.0% and below or equal to 10.0% (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Body Mass Index (BMI) below or equal to 40.0 kg/m^2

Key exclusion criteria (5 listed)

Treatment with any thiazolidinedione (TZD) and glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to Visit 1 (screening)
Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Impaired kidney function with serum creatinine above or equal to 133 micromol/L (1.5 mg/dL) for males and above or equal to 124 micromol/L (1.4 mg/dL) for females (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure higher or equal to 180 mmHg and/or diastolic blood pressure higher or equal to 100 mmHg)
Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations) or bolus insulin. Previous use of pre-mixed or bolus insulin products was allowed only in case of hospitalisation or a severe condition requiring intermittent use of pre-mixed or bolus insulin products for less than 14 consecutive days, but not during the last 3 months prior to screening visit (Visit 1)

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
biphasic insulin aspart 30Administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued.	Drug	Investigator-driven titration BIAsp 30 (BID) + metformin, Subject-driven titration BIAsp 30 (BID) + metformin

Primary outcome

Change in HbA1c (Glycosylated Haemoglobin) - FAS
Time frame: Week 0, week 20
Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in full analysis set (FAS).
Change in HbA1c (Glycosylated Haemoglobin) - PP
Time frame: Week 0, week 20
Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in per protocol (PP) analysis set.

5 secondary outcomes

Change in Fasting Plasma Glucose (FPG) (Central Laboratory Values)
Time frame: Week 0, week 20
Number of Treatment Emergent Hypoglycaemic Episodes
Time frame: Week 0 to week 20
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
Time frame: Week 0
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
Time frame: Week 4
Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score
Time frame: Week 20

Results and safety

Results posted to the registry on 12 Sep 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Subject-driven	174	165
Investigator-driven	174	157

Primary outcome: Change in HbA1c (Glycosylated Haemoglobin) - FAS

Time frame: Week 0, week 20. Least squares mean (Standard Error). Unit: percentage of glycosylated haemoglobin

Measure	Subject-driven n = 169	Investigator-driven n = 166
Value	-0.72 (0.08)	-0.97 (0.08)

Subject-driven vs Investigator-driven: Estimated treatment difference, Mean: 0.25 (95% CI 0.04 to 0.46), Regression, Linear

Population analysed: Full analysis set (FAS) - analysis included endpoint derived after 20 Weeks of treatment and missing data was imputed using last observation carried forward (LOCF) where any post-baseline measurements were available. 13 subjects did not contribute to the statistical analysis after Week 20.

Primary outcome: Change in HbA1c (Glycosylated Haemoglobin) - PP

Time frame: Week 0, week 20. Least squares mean (Standard Error). Unit: percentage of glycosylated haemoglobin

Measure	Subject-driven n = 164	Investigator-driven n = 160
Value	-0.71 (0.08)	-0.98 (0.08)

Subject-driven vs Investigator-driven: Estimated treatment difference, Mean: 0.26 (95% CI 0.05 to 0.48), Regression, Linear

Population analysed: Per protocol (PP) analysis set - analysis included subjects exposed to BIAsp 30 for more than 12 weeks without any major protocol violations. 24 subjects did not contribute to the statistical analysis after Week 20.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were captured from the time of consent until 20 weeks of treatment, and if needed, were followed-up after the final visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Subject-driven	2 of 174 (1.1%)	0 of 174 (0%)	Not reported
Investigator-driven	3 of 173 (1.7%)	0 of 173 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25180608Gao Y, Luquez C, Lynggaard H, Andersen H, Saboo B. The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration. Curr Med Res Opin. 2014 Dec;30(12):2483-92. doi: 10.1185/03007995.2014.960512. Epub 2014 Sep 29.
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

41 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing biphasic insulin aspart 30 in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 41 sites in 6 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 8 inclusion and 5 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 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in India, Poland, Spain, United Kingdom, China and 1 more country. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 12 Sep 2013). 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?

Change in HbA1c (Glycosylated Haemoglobin) - FAS (time frame: Week 0, week 20). The study lists 2 primary outcomes in all. 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 NCT01427920, 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 24 Feb 2017.