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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01519674




Registration number
NCT01519674
Ethics application status
Date submitted
24/01/2012
Date registered
27/01/2012
Date last updated
24/02/2017

Titles & IDs
Public title
Treatment Intensification With Biphasic Insulin Aspart 30 in Subjects With Type 2 Diabetes Inadequately Controlled on Sitagliptin and Metformin
Scientific title
A 24 Week Randomised, Open Label, 3 Parallel-group Comparison of Once and Twice Daily Biphasic Insulin Aspart (BIAsp) 30 Plus Sitagliptin and Twice Daily BIAsp 30, All in Combination With Metformin in Insulin naïve Type 2 Diabetic Subjects Inadequately Controlled on Sitagliptin and Metformin
Secondary ID [1] 0 0
U1111-1125-0850
Secondary ID [2] 0 0
BIASP-3963
Universal Trial Number (UTN)
Trial acronym
SIT2MIX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 0 0
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - biphasic insulin aspart 30
Treatment: Drugs - biphasic insulin aspart 30
Treatment: Drugs - sitagliptin
Treatment: Drugs - metformin

Active comparator: BIAsp 30 BID + sitagliptin + metformin -

Active comparator: BIAsp 30 BID + metformin -

Active comparator: BIAsp 30 OD + sitagliptin + metformin -


Treatment: Drugs: biphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) twice daily. Individually adjusted dose.

Treatment: Drugs: biphasic insulin aspart 30
BIAsp 30 will be injected subcutaneously (under the skin) once daily. Individually adjusted dose.

Treatment: Drugs: sitagliptin
Subjects will continue on their pre-trial sitagliptin treatment.

Treatment: Drugs: metformin
Subjects will continue on their pre-trial metformin treatment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Timepoint [1] 0 0
Week 0 to Week 24
Secondary outcome [1] 0 0
Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%)
Timepoint [1] 0 0
After 24 weeks of treatment
Secondary outcome [2] 0 0
Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c = 6.5%)
Timepoint [2] 0 0
After 24 weeks of treatment
Secondary outcome [3] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG)
Timepoint [3] 0 0
Week 0 to Week 24
Secondary outcome [4] 0 0
Prandial Plasma Glucose (PPG) Increments at Breakfast
Timepoint [4] 0 0
After 24 weeks of treatment
Secondary outcome [5] 0 0
Prandial Plasma Glucose (PPG) Increments at Lunch.
Timepoint [5] 0 0
After 24 weeks of treatment
Secondary outcome [6] 0 0
Prandial Plasma Glucose (PPG) Increments at Dinner.
Timepoint [6] 0 0
After 24 weeks of treatment
Secondary outcome [7] 0 0
Prandial Plasma Glucose (PPG) Overall Mean Increment.
Timepoint [7] 0 0
After 24 weeks of treatment
Secondary outcome [8] 0 0
Adverse Events (AEs)
Timepoint [8] 0 0
Week 0 to Week 24
Secondary outcome [9] 0 0
Number of Treatment Emergent Hypoglycaemic Episodes (Nocturnal and Day-time) Classified Both According to the American Diabetes Association (ADA) Definition and to an Additional Definition for Minor Episodes.
Timepoint [9] 0 0
Week 0 to Week 24
Secondary outcome [10] 0 0
Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes.
Timepoint [10] 0 0
Week 0 to Week 24

Eligibility
Key inclusion criteria
* Diagnosed with type 2 diabetes for a minimum of 6 months prior to screening (Visit 1)
* Stable treatment with a total daily dose of at least 1000 mg of metformin (with or without additional oral anti-diabetic drugs (OADs) treatment). The metformin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
* Stable treatment with a total daily dose of at least 100 mg sitagliptin. The sitagliptin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
* Subject is insulin-naïve (never previously treated with insulin). (However, short term insulin use due to intermittent illness of up to 14 days or insulin treatment for gestational diabetes is allowed)
* HbA1c (glycosylated haemoglobin) between 7.0 to 10.0 % (53-86 mmol/mol) (both inclusive) by central laboratory analysis demonstrating inadequate control on sitagliptin and metformin (with or without other OADs)
* Body Mass Index (BMI) below or equal to 40.0 kg/m^2
* Able and willing to eat at least 2 meals (breakfast and dinner) every day during the trial
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with thiazolidinedione (TZD) or glucagon-like-peptide-1 (GLP-1) receptor agonist within the last 3 months prior to screening (Visit 1)
* Cardiac disease within the last 6 months prior to screening (Visit 1), defined as: decompensated heart failure New York Heart Association (NYHA) class III or IV; unstable angina pectoris; or myocardial infarction
* Severe hypertension, systolic blood pressure equal to or above 180 mm Hg or diastolic blood pressure equal to or above 100 mm Hg, after 5 minutes rest in the sitting position using mean value of 3 measurements at screening (Visit 1)
* Anticipated change of dose of any systemic treatment with products, which in the trial physician's opinion could interfere with glucose metabolism (e.g., systemic corticosteroids)
* Clinically significant diseases (except for conditions associated with type 2 diabetes) which, in the trial physician's opinion may confound the results of the trial or pose additional risk in administering trial product(s)
* Impaired hepatic function as indicated by aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) above 2.5 times the upper normal range, according to central laboratory reference ranges
* Impaired renal function as indicated by serum creatinine levels equal to or above 133 micromol/L (1.5 mg/dL) for males and equal to or above 124 micromol/L (1.4 mg/dL) for females or estimated creatinine clearance below 60 mL/min, based on the Cockroft & Gault formula and according to local practise for metformin use

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2013
Sample size
Target
Accrual to date
Final
582
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Broadmeadow
Recruitment hospital [2] 0 0
Novo Nordisk Investigational Site - Coffs Harbour
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Caba
Country [3] 0 0
Argentina
State/province [3] 0 0
Mar del Plata
Country [4] 0 0
Argentina
State/province [4] 0 0
Morón
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Brazil
State/province [6] 0 0
Brasília
Country [7] 0 0
Brazil
State/province [7] 0 0
Curitiba
Country [8] 0 0
Brazil
State/province [8] 0 0
Fortaleza
Country [9] 0 0
Brazil
State/province [9] 0 0
Porto Alegre
Country [10] 0 0
Greece
State/province [10] 0 0
Alexandroupolis
Country [11] 0 0
Greece
State/province [11] 0 0
Athens
Country [12] 0 0
Greece
State/province [12] 0 0
Thessaloniki
Country [13] 0 0
India
State/province [13] 0 0
Andhra Pradesh
Country [14] 0 0
India
State/province [14] 0 0
Gujarat
Country [15] 0 0
India
State/province [15] 0 0
Karnataka
Country [16] 0 0
India
State/province [16] 0 0
Kerala
Country [17] 0 0
India
State/province [17] 0 0
Maharashtra
Country [18] 0 0
India
State/province [18] 0 0
Punjab
Country [19] 0 0
India
State/province [19] 0 0
Tamil Nadu
Country [20] 0 0
India
State/province [20] 0 0
Uttar Pradesh
Country [21] 0 0
India
State/province [21] 0 0
West Bengal
Country [22] 0 0
India
State/province [22] 0 0
New Delhi
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Goyang
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Jeonju
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Pusan
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Pyungchon-Dong 896, Dongan-Gu
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Suwon
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Ulsan
Country [30] 0 0
Malaysia
State/province [30] 0 0
Penang
Country [31] 0 0
Malaysia
State/province [31] 0 0
Seremban
Country [32] 0 0
Portugal
State/province [32] 0 0
Coimbra
Country [33] 0 0
Portugal
State/province [33] 0 0
Lisboa
Country [34] 0 0
Portugal
State/province [34] 0 0
Matosinhos
Country [35] 0 0
Portugal
State/province [35] 0 0
Porto
Country [36] 0 0
Thailand
State/province [36] 0 0
Bangkok
Country [37] 0 0
Thailand
State/province [37] 0 0
Chiang Mai
Country [38] 0 0
Thailand
State/province [38] 0 0
Khon Kaen
Country [39] 0 0
Turkey
State/province [39] 0 0
Antalya
Country [40] 0 0
Turkey
State/province [40] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial is conducted in Asia, Europe, Oceania and South America. The aim of this clinical trial is to generate data demonstrating how to intensify diabetes treatment using BIAsp 30 (biphasic insulin aspart 30) by adding or substituting BIAsp 30 to sitagliptin in various regimens for type 2 patients inadequately controlled on sitagliptin and metformin (with or without other oral anti-diabetic drugs (OADs)).

The trial is conducted as a phase 4 trial in the majority of the participating countries. However, in some countries the trial is conducted as phase 3b.
Trial website
https://clinicaltrials.gov/study/NCT01519674
Trial related presentations / publications
Linjawi S, Sothiratnam R, Sari R, Andersen H, Hiort LC, Rao P. The study of once- and twice-daily biphasic insulin aspart 30 (BIAsp 30) with sitagliptin, and twice-daily BIAsp 30 without sitagliptin, in patients with type 2 diabetes uncontrolled on sitagliptin and metformin-The Sit2Mix trial. Prim Care Diabetes. 2015 Oct;9(5):370-6. doi: 10.1016/j.pcd.2014.11.001. Epub 2014 Dec 3.
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Registry (GCR, 1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01519674