Download Preparation of an Observational Study Report

NovoMix® 30
Study ID: BIAsp-3557
Observational Study Report
Report Abstract
2
Date:
Version:
Status:
Page:
02-Nov-2010
2
Final
1 of 4
Abstract
Study Registration ID-number:
ClinicalTrials.gov Identifier:
NCT00699179
EudraCT-number
NA
TITLE OF STUDY
EFFECTIVE – EFFicacious glycaEmia Control, Treatment goal achIevement Very
simplE with NovoMix® 30:
A single-country, multicentre, prospective, open label, non-controlled,
observational, 26-week study in Serbian patients using NovoMix® 30 (biphasic
insulin aspart 30) for treatment of Diabetes Mellitus in everyday clinical practice
INVESTIGATOR(S)
Aleksandrić Svetlana, Anđelić -Jelić Marina, Anđelković Zoran, Bećarević-Basta
Zagorka, Beljić Teodora, Burić Bogdan, Čaparević Zorica, Ćilerdžić Lazić Tatjana,
Ćirić Kovina, Cvetičanin Anica, Dekić Jasna, Desnica Nikola, Đorđević Jovanka,
Dragović Tamara, Đurić-Pejović Branka, Đurović Suzana, Dželetović Gordana,
Hajduković Zoran, Ilić Sanja, Ilić Tatjana, Ilić Vesna, Jelić Svetlana, Jeremić
Ljiljana, Jojić Biljana, Kitaresku Đorđe, Kostić Nada, Kulović- Manojlović Svetlana
Lazarević Prvoslav, Malenković Jelica, Manov Nebojša, Marinković Bogdana,
Marković Marija, Marošanin Olga, Medić Violeta, Medin-Davidović Mila, Mihajlović
Slovenka, Milenković Koviljka, Mileusnić Đurdev Miroslava, Miljević Jovan,
Milošević - Matić Gordana, Milovanović Bratislav, Milović Mirjana, Miludinović
Gordana, Mišić Svetislav, Miškeljin Milinko, Mitić Andelka, Mitov Slavoljub,
Mitrović-Perišić Nataša, Mujagić Muradija, Naumović Jasna, Nedeljković Milinka,
Nenadović Radmila, Nikolić Vera, Pavlović Jovica, Perovic Milan, Popović Mira,
Popović Srđan, Prvulović Snežana, Pudar Georgina, Radosavljević Branislava,
Radulović Ljubivoje, Ristić Dafina, Selea Anujka, Softić Suad, Spasić Slađana,
Sretenović Nikola, Srnka Jasmina, Stefanović Ljiljana, Stefanović Nikola,
Stoiljković Miroljub, Stoiljković-Tomić Olivera, Stojanović Dejan, Stojanović
Snežana, Stojčić Dragana, Stošic Srdjan, Suljić Muamer, Tavčar Ivan, ToljićŠuluburić Dušica, Vasilić Kokotović Olivera, Vekić Ana, Veličković Rada, Veličković
Sonja, Vircburger Miroslav, Živković Milan, Živojinović Dragana, Zlatković Silva,
Zogović Mirjana, Vlade Veličković, Rozajlija Kormanjoš Senti, Tatjana Koić
Prašević, Snežana Đorđević, Dragana Belović- Milovanović, Goran Janjić,
Snežana Grozdanović, Olgica Obradović, Bodiroga Tanja, Antić Slobodan, Burazor
Zorka, Dimić Dragan, Đorđević Dušan, Karapandžić Katarina, Kocić Radivoj,
Kostić Sonja, Pešić Milica, Radenković Saša, Radojković Danijela, Ristić - Potić
Radmila, Strahinjić Tijana, Šaranac Ljiljana, Veličković Mirjana, Velojić Golubović Milena, Vukadinović Selena, Vukanović Živka, Živić Saša, Pejčić Filip,
Atanasković Zorica, Obradović Ljiljana, Aleksić Aleksandar, Đorđević Miodrag,
Đinđić Ljiljana, Jovanović Miroljub, Lalić Nebojša, Jotić Aleksandra, Miličić Tanja,
Lukić Ljiljana, Zamaklar Miroslava, Lalić Katarina, Dragašević Mirjana, Rajković
Nataša, Drašković Danijela, Popović Ljilljana, Micić Dragan, Kendereški
Aleksandra, Šumarac Dumanović Mirjana, Pejković Stamenković Danica, Cvijović
Goran, Zorić Svetlana, Popović Srđan, Srećković Dimitrijević Vesna, Gostiljac
Draško, Milić Gordana, Nišić Tanja, Ilić Miroljub, Damjanović Svetozar, Petakov
Milan, Macut Đuro, Popović Vera, Đurović Marina, Miljić Dragana, Trbojević Božo,
Žarković Miloš, Ćirić Jasmina, Beleslin Biljana, Stojković Mirjana, Savić Slavica,
Drezgić Milka, Vujović Svetlana, Ivović Miomira, Tančić Milina, Pavlović Miloš,
Ćirić Slavica, Josipović Aleksandra, Popović Dragana, Đomlija Radojka, Peruško
Stojanović Radmila, Bjekić Jelica, Rašić Milutinović Zorica, Gluvić Zoran, Popović
Radinović Vesna, Tica Jelena, Vujović Marina, Nedeljković Milinka, Marošanin
Novo
Nordisk
NovoMix® 30
Study ID: BIAsp-3557
Observational Study Report
Report Abstract
Date:
Version:
Status:
Page:
02-Nov-2010
2
Final
2 of 4
Olga, Bogićević Zlata, Bugarčić Stanić Olgica, Mrdović Sonja, Vilus Ljubica,
Pavlović Marina, Stanković Zoran, Jovanović Miroljub, Đukić Aleksandar,
Metiljević Slobodanka, Bajović Ljiljna, Mladenović Violeta, Đokić Ivana, Petrović
Jelena, Bubonja Dragana, Stojanović Miroslav, Stojanović Jasmina, Mitić Milica,
Milosavljević Rada, Davidović Vesna, Krsmanović Rade, Milenković Dragoslav,
Vučković Zorica, Tomić Saša, Ristić Marija, Stošić Anđelka, Stevanović Radmila,
Stanojković Tatjana, Janko Marković, Pantelinac Pavle, Đilas Todorović Ljiljana,
Tatjana Ivković Lazar, Tešić Dragan, Stokić Edita, Medić-Stojanoska Milica,
Mitrović Milena, Mak Karaba Irena, Radisavljević Zorica, Pejin Radoslav, Dragana
Tomić Naglić, Stojšić Dragan, Milan Uzelac, Biljana Nikolić, Mile Novković,
Snežana Polovina, Klara Tucić-Nemet, Opsenica-Skendžić Mira, Karadžić Katica
STUDY SITE(S)
69 Serbian sites were included in the study.
PUBLICATIONS
NA
STUDY PERIOD
DEVELOPMENT PHASE
8 January 2008 to 29 December 2009
Observational Study
OBJECTIVES
Primary Objective: The primary objective of this study is to evaluate the
glycaemic control as measured by HbA1c using NovoMix® 30 (biphasic insulin
aspart 30) for treatment of Type 1 or Type 2 Diabetes Mellitus under normal
clinical practice conditions in Serbia
Secondary Objectives:
• To evaluate level of glycaemic control by percentage of patients to reach
HbA1c < 7.5% for Type 1 Diabetes Mellitus, < 7.0% and ≤ 6.5% for Type
2 Diabetes Mellitus, at approximately 12 weeks and 26 weeks of
treatment, as per National Guideline for Clinical Practice for Type 1 and
Type 2 Diabetes Mellitus and American Diabetes Association (ADA)
recommendations for HbA1C targets.
• Glucose variability as measured by FPG at approximately 12 weeks and
26 weeks of treatment
• Postprandial glycaemic control as measured by PPG at approximately 12
weeks and 26 weeks of treatment
• Insulin dose and number of injections at approximately 12 weeks and 26
weeks of treatment
• Oral antidiabetic concomitant drug therapy dosage at approximately 12
weeks and 26 weeks of treatment, and eventual discontinuation of the
oral antidiabetic drug therapy during the study
• Body weight and waist circumference at approximately 12 weeks and 26
weeks of treatment
• Number of major hypoglycaemic events during 4 weeks proceeding
routine visits at approximately 12 weeks and 26 weeks of treatment
• Number of adverse drug reactions (ADR) after approximately 12 weeks
and 26 weeks of treatment
METHODOLOGY
This was a single-country, multicentre, prospective, open label, non-controlled,
observational, 26-week study in patients using NovoMix® 30 (biphasic insulin
aspart 30) for the treatment of Type 1 or Type 2 Diabetes Mellitus in Serbia.
NUMBER OF PARTICIPANTS PLANNED AND ANALYSED
A sample size of approximately and up to 3000 patients is proposed to be
included in order to reflect the post-authorisation experience with insulin
analogue (biphasic insulin aspart 30) when used under normal clinical practice
conditions in Serbia. The full analysis set (FAS) consisted of 2308 participants.
Novo
Nordisk
NovoMix® 30
Study ID: BIAsp-3557
Observational Study Report
Report Abstract
Date:
Version:
Status:
Page:
02-Nov-2010
2
Final
3 of 4
The extended effectiveness analysis set (EEAS) consists of 2256 participants.
DIAGNOSIS AND MAIN CRITERIA FOR INCLUSION
Patients treated by Serbian physicians who prescribe insulin. Any patient with
Type 1 or Type 2 Diabetes Mellitus who has inadequeate glycaemic control after
being treated with human insulins for (at least) last 6 months, evaluated by
HbA1c>7%, and upon endocrinologist or internist opinion is eligible for the
study. The selection of the patients will be at the discretion of the individual
physician based on clinical judgement, prior to study start.
TEST PRODUCT, DOSE AND MODE OF ADMINISTRATION
NovoMix® 30 (biphasic insulin aspart 30) 3 ml FlexPen® pre-filled pen (100
U/ml). NovoMix® 30 (biphasic insulin aspart 30) manufactured by Novo Nordisk
A/S, DK-2880 Bagsværd, Denmark.
DURATION OF TREATMENT
Planned study duration was 26 weeks. The actual treatment duration during this
study was between 2 weeks and 6 months.
CRITERIA FOR EVALUATION - EFFECTIVENESS
HbA1c, Preprandial glycemia, Postprandial glycaemic control, Oral antidiabetic
concomitant drug therapy dosage, Body weight, waist circumference
CRITERIA FOR EVALUATION - SAFETY
Insulin dose and number of injections, Oral antidiabetic concomitant drug
therapy dosage, Number of major hypoglycaemic events and Number of adverse
drug reactions.
STATISTICAL METHODS
Statistical testing (comparison of before and after biphasic insulin aspart 30)
was performed with paired t-tests for continuous variables like mean HbA1c,
mean FPG, mean PPG, mean weight and mean waist circumference. No interim
analysis was performed. Comparison of number of hypoglycaemic events before
and after biphasic insulin aspart 30 was performed with Wicoxon signed rank
test.
DEMOGRAPHY OF STUDY POPULATION
The mean age was 60.5 years. Fifty-eight (58%) of the patients was female.
The mean weight was 81.2 kg and the mean BMI was 28.6 kg/m2. The mean
duration of diabetes Type 2 was 12.4 years, the mean HbA1c value was 9.68 %
and the mean Preprandial glycemia in the FAS was 10.64 mmol/L. Most patients
suffered from diabetes Type 2(>=95.5%). The median duration of having
diabetes Type 2 was 11-12 years.
EFFECTIVENESS RESULTS
Overall HbA1c percentages decreased significantly with 1.25% and 2.03% after
12 and 26 weeks respectively (both p<0.0001). About 15% of the patients with
Type 2 diabetes achieved HbA1c values below 7.0 % after 26 weeks of
treatment. Seven (7%) percent of the patients reached even lower levels that
were equal or below 6.5 %. In addition, at the end of the study FPG values had
decreased sigificantly (p<0.0001) with 3.43 mmol/l and
postprandial glycaemia after breakfast decrease significantly (p<0.0001) with
4.24 mmol/l.
Novo
Nordisk
NovoMix® 30
Study ID: BIAsp-3557
Observational Study Report
Report Abstract
Date:
Version:
Status:
Page:
02-Nov-2010
2
Final
4 of 4
SAFETY RESULTS
Most of the patients used NovoMix® twice daily (68.1% at 12 weeks and 58.9%
at 26 weeks). The number of subjects with a three times a day regimen
increased to 36.6% at the end of the study. A significant mean increase
(p<0.0001) in recommended dose of 4.6 U/ml was observed during the study.
The mean actual dose at the end of the study was 48.2 U/ml. Additional
oral antihyperglycemic therapy was given for 67% of the patient. This percent
increased to 74% at the final visit (26 weeks). Most of these patients took
Metformin (up to 69% of all patients at the end of the study).
No adverse drug reactions were reported. The number of hypoglaemic events
observed by individual subjects decreased significantly (p-value<0.0001) and
the total number of subjects experiencing these events decreased from 19% to
7.4%.
CONCLUSIONS
The beneficial effect of NovoMix® 30 is confirmed with this study. At the end of
the study, the patients showed significant decreases in HbA1c values from
baseline (p<0.0001) of 2.03%. Around 15% of the patients with Type 2
diabetes achieved target HbA1c value <7.0% and 6.6% ≤ 6.5%. In addition,
FPG values decreased sigificantly (p<0.0001) with 3.43 mmol/l and
postprandial glycaemia (PPG) after breakfast (p<0.0001) with 4.24 mmol/L.
Moreover, slight but significant decreases were observed in weight (-0.84 kg)
and waist circumference (-1.2 cm). Finally, the number of hypoglaemic events
observed by individual subjects decreased significantly (p-value<0.0001) and
the total number of subjects experiencing these events decreased from 19% to
7.4%.
The study was conducted in accordance with the Declaration of Helsinki, Oct.
2008 and Good Pharmacoepidemiology Practice, Rev. 2: Apr. 2007.
Novo
Nordisk