Clinical trial NCT01519674: Treatment Intensification With Biphasic Insulin Aspart 30 in Subjects With Type 2 Diabetes Inadequately Controlled on Sitagliptin and Metformin
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2012-01-27
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0 to Week 24
Secondary outcomes:
measure: Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c < 7.0%)
timeFrame: After 24 weeks of treatment
measure: Responder for HbA1c, Proportion of Subjects Achieving Pre-defined HbA1c Targets (HbA1c ≤ 6.5%)
timeFrame: After 24 weeks of treatment
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Week 0 to Week 24
measure: Prandial Plasma Glucose (PPG) Increments at Breakfast
timeFrame: After 24 weeks of treatment
measure: Prandial Plasma Glucose (PPG) Increments at Lunch.
timeFrame: After 24 weeks of treatment
measure: Prandial Plasma Glucose (PPG) Increments at Dinner.
timeFrame: After 24 weeks of treatment
measure: Prandial Plasma Glucose (PPG) Overall Mean Increment.
timeFrame: After 24 weeks of treatment
measure: Adverse Events (AEs)
timeFrame: Week 0 to Week 24
measure: 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.
timeFrame: Week 0 to Week 24
measure: Change From Baseline in Patient Reported Outcome by Use of the Treatment Related Impact Measure - Diabetes.
timeFrame: Week 0 to Week 24
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mar del Plata
country: Argentina
facility: Novo Nordisk Investigational Site
city: Morón
country: Argentina
facility: Novo Nordisk Investigational Site
city: Broadmeadow
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Brasília
country: Brazil
facility: Novo Nordisk Investigational Site
city: Curitiba
country: Brazil
facility: Novo Nordisk Investigational Site
city: Fortaleza
country: Brazil
facility: Novo Nordisk Investigational Site
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
city: Alexandroupolis
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Calicut
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Trivandrum
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Nagpur
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Amritsar
country: India
facility: Novo Nordisk Investigational Site
state: Punjab
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Trichy
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kanpur
country: India
facility: Novo Nordisk Investigational Site
state: Uttar Pradesh
city: Noida
country: India
facility: Novo Nordisk Investigational Site
state: Uttar Pradesh
city: Varanasi
country: India
facility: Novo Nordisk Investigational Site
state: Uttar Pradesh
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: New Delhi
country: India
facility: Novo Nordisk Investigational Site
city: Goyang
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Jeonju
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Pusan
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Pyungchon-Dong 896, Dongan-Gu
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Suwon
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Ulsan
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Penang
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Seremban
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Coimbra
country: Portugal
facility: Novo Nordisk Investigational Site
city: Lisboa
country: Portugal
facility: Novo Nordisk Investigational Site
city: Lisboa
country: Portugal
facility: Novo Nordisk Investigational Site
city: Lisboa
country: Portugal
facility: Novo Nordisk Investigational Site
city: Matosinhos
country: Portugal
facility: Novo Nordisk Investigational Site
city: Porto
country: Portugal
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Chiang Mai
country: Thailand
facility: Novo Nordisk Investigational Site
city: Khon Kaen
country: Thailand
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: 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.