A randomized, two-armed, parallel, double-blind, active-controlled, non-inferiority clinical trial to compare efficacy and safety of test-liraglutide (CinnaGen Co., Iran) to innovator liraglutide product (Victoza®, Novo Nordisk, Denmark) in patients with type II diabetes (T2D)
Comparing the efficacy and safety of Cinnagen liraglutide and Novo Nordisk Victoza® in type II diabetes patients
Design
randomized, two-armed, parallel, double-blind, active-controlled, non-inferiority clinical trial of 300 type II diabetes patients
Settings and conduct
2 cities (Tehran and Karaj) and 16 centers will participate in this study. The patients will be included in the study after declaring informed consent and meeting specific inclusion/exclusion criteria. Initially, the patients will be given a randomization code and will be allocated randomly to one of the two intervention groups. The study drugs will be used in exact identical shape, box, and labels so the investigator, the patient, and data analyzer will be completely unaware of the drug which certain patient has received. Subsequently, the patient will be injected daily and Evaluation and clinical examination will be performed in 7 visits and will be monitored for 6 months after the first injection.
Participants/Inclusion and exclusion criteria
Type II diabetes patients receiving maximum dose metformin and at least half of maximum dose insulin-secretagogues; 30–65 years old; 7.5≤HbA1c<10; BMI: 20-45 Kg/m2 and informed consent; no Hypersensitivity to liraglutide or any formulation component, no Insulin treatment during the previous 3 months; Impaired liver or renal function:Uncontrolled hypertension; Malignancy;History or family history of Medullary Thyroid Carcinoma or Multiple endocrine neoplasia syndrome type 2; History of pancreatic cancer and pancreatitis; Recent MI; Pregnancy or Previous exposure to exenatide or liraglutide.
Intervention groups
either liraglutide (cinnagen) or victoza group receive 0.6 mg/day subcutaneous liraglutide for a week and then 1.2 mg/day up to 3 weeks and finally 1.8 mg/day to the end of week 26
Main outcome variables
Change in HbA1c after 26 weeks of treatment
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N15
Registration date:2019-09-13, 1398/06/22
Registration timing:registered_while_recruiting
Last update:2019-09-13, 1398/06/22
Update count:3
Registration date
2019-09-13, 1398/06/22
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2019-06-10, 1398/03/20
Expected recruitment end date
2020-11-10, 1399/08/20
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A randomized, two-armed, parallel, double-blind, active-controlled, non-inferiority clinical trial to compare efficacy and safety of test-liraglutide (CinnaGen Co., Iran) to innovator liraglutide product (Victoza®, Novo Nordisk, Denmark) in patients with type II diabetes (T2D)
Public title
Comparing Efficacy and Safety of CinnaGen-liraglutide Versus Victoza® in Patients with Type II Diabetes
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Subjects with Type II diabetes treated with two oral glucose-lowering agents (OGLAs; Metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues) with at least half of the maximum dose for that agent for equal or greater than 3 months
30–65 years of age
HbA1c equal or greater than 7.5 and smaller than 10
Body mass index (BMI) of 20-45 kg/m2
Exclusion criteria:
Lack of consent for being in the trial and not complying with 26-weeks follow-up period
Hypersensitivity to liraglutide or any component of the formulation (excipients include Disodium phosphate dehydrate, Propylene glycol, Phenol, Water for injection)
Insulin treatment during the previous 3 months (except short-term treatment for intercurrent illness)
Impaired liver function (alanine aminotransferase concentrations equal to or greater than 2.5 times upper normal range).
Impaired renal function (eGFR smaller than 60 mL/min/1.73 m2)
Uncontrolled hypertension (equal or greater than 160/100 mmHg)
Malignancy
Using any drugs apart from OGLAs likely to affect glucose concentrations, including androgens, hyperglycemia-associated agents, hypoglycemia-associated agents, MAO inhibitors, quinolone antibiotics, salicylates (Anti-inflammatory dose).
Treatment with dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors)
Treatment with systemic corticosteroids within last three months
History or family history of Medullary Thyroid Carcinoma (MTC)
Multiple endocrine neoplasia syndrome type 2 (MEN2)
History of pancreatic cancer and pancreatitis
History of recent MI within 3 months, uncontrolled CHF, and unstable Angina
History or known case of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy
pregnancy
Previous exposure to exenatide or liraglutide.
Age
From 30 years old to 65 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
300
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization plan of the patients will be carried out centrally using an R-CRAN software version 3.2.3. Blocks (with the size 2 or 4) will be made using permuted block randomization for a total of 300 patients (1:1 allocation ratio). After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of first name, first two letters of surname) and 4 numbers (center code). Moreover, the described code is followed by study unique identification code consisting of first two letters of the generic name of the investigational product and study phase number, respectively (LI3), and four numbers (corresponding to the randomization number), e.g. ABCD0001LI3-0001.
The randomization number will be assigned in a consecutive way.
Blinding (investigator's opinion)
Double blinded
Blinding description
The medication compartment of both Victoza® and test-liraglutide (CinnaGen) will be placed in similar pen-injector containers, in a way that they cannot be differentiated by the appearance. Additionally, people who review the results and analyze the data will be blinded to patients’ allocation to treatment arms.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
1
Registry name
ClinicalTrial.gov
Secondary trial Id
NCT03421119
Registration date
2018-02-02, 1396/11/13
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Iran University of Medical Sciences
Street address
Near Milad Tower, Shahid Hemmat Highway
City
Tehran
Province
Tehran
Postal code
1449614535
Approval date
2019-01-23, 1397/11/03
Ethics committee reference number
IR.IUMS.REC.1396.31731
2
Ethics committee
Name of ethics committee
Ethics Committee of Alborz University of Medical Sciences
Adverse events with special focus on the incidence, severity, and duration of gastrointestinal disturbances, nausea, vomiting, diarrhea; kidney function (BUN, SCr), liver function (ALT, AST, ALP), serum levels of Amylase and Lipase, tachycardia/palpitation, and antibody formation
Liraglutide (produced by CinnaGen Co.) pen-injector (18 mg/3 ml), subcutaneous injection of 0.6 mg every day for one week, followed by a dose of 1.2 mg per day for up to three weeks. Then, 1.8 mg daily subcutaneous injection will be performed until the end of week 26.
Category
Treatment - Drugs
2
Description
Victoza® (produced by Novo Nordisk Company) pen-injector (18 mg/3 ml), subcutaneous injection of 0.6 mg every day for one week, followed by a dose of 1.2 mg per day for up to three weeks. Then, 1.8 mg daily subcutaneous injection will be performed until the end of week 26.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Institute of Endocrinology and Metabolism Research andTraining Center
Full name of responsible person
Mohammad Ebrahim Khamseh
Street address
Behafarin ST, Karimkhan AVE, Vali-asr Sq
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 8894 5246
Fax
+98 21 8894 5173
Email
m.e.khamseh@gmail.com
2
Recruitment center
Name of recruitment center
Dr Esteghamati Office
Full name of responsible person
Alireza Esteghamati
Street address
Unit 13, 2nd floor, ebne sina Building, before shariati St, motahhari St
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 8841 7918
Fax
Email
Esteghamati@tums.ac.ir
3
Recruitment center
Name of recruitment center
Dr Mohajerani Office
Full name of responsible person
Mohammadreza Mohajeri Tehrani
Street address
No.103, Shokr-allah St, In front of Tehran Heart Center, North Kargar Ave
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 8802 5450
Email
Mrmohajeri@tums.ac.ir
4
Recruitment center
Name of recruitment center
Shahid Rajaei Hospital
Full name of responsible person
Zahra Ghaem maghami
Street address
Valiasr Ave, Niayesh Intersection
City
tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 2392 2197
Email
zahra_ghaem2000@yahoo.com
5
Recruitment center
Name of recruitment center
Dr Monavari Office
Full name of responsible person
Arezou monavari
Street address
No. 11, Bahar Medical building, Shahid taheri Alley, Bahar Ave
City
karaj
Province
Alborz
Postal code
1593748711
Phone
+98 26 3225 6438
Email
Dr_a_mon@yahoo.com
6
Recruitment center
Name of recruitment center
Taban Clinic
Full name of responsible person
Ramin malbousbaf
Street address
No.100, End of Derakhti Blvd, Dadman Blvd, Shahrak-e-Qarb
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 2237 7250
Email
ramin_baf@yahoo.com
7
Recruitment center
Name of recruitment center
Dr Zamanzadeh Office
Full name of responsible person
Mehran Zaman zadeh
Street address
No.10, third floor, Tooran(135) medical building, West hoveyzeh St, North Sohrevardi
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 8874 7090
Email
dr_mzamanzadeh@yahoo.com
8
Recruitment center
Name of recruitment center
Dr Hossein Panah Office
Full name of responsible person
Farhad hosein panah
Street address
No. 178, Lower Tehran Clinic, Ghaem Magham Street
City
Tehran
Province
Tehran
Postal code
1593748711
Phone
+98 21 4425 7406
Email
Farhad.hosseinpanah@gmail.com
9
Recruitment center
Name of recruitment center
Dr Khannakhjavani Office
Full name of responsible person
Manouchehr Khan Nakhjavani
Street address
No. 82, Fajr Street (Jam), Motahhari Street
City
Tehran
Province
Tehran
Postal code
1487474884
Phone
+98 21 8883 0323
Email
nakhjavanim@tums.ac.ir
10
Recruitment center
Name of recruitment center
Personal Office
Full name of responsible person
Amir Kamran Nikoosokhan
Street address
First Floor, No. 17, Shohada Alley, Above Motahhari, Mirzaee Shirazi Street
City
Tehran
Province
Tehran
Postal code
1493846644
Phone
+98 21 8872 8237
Email
amirkamranniko@yahoo.com
11
Recruitment center
Name of recruitment center
Lolagar Hospital
Full name of responsible person
Zahra Banazadeh
Street address
South Khosh street, diabetes st
City
Tehran
Province
Tehran
Postal code
1492374646
Phone
+98 21 6683 5000
Email
zbanazadeh01@gmail.com
12
Recruitment center
Name of recruitment center
Personal Office
Full name of responsible person
Hassan Ganjizadeh
Street address
No. 52, Fathi Shaghaghi Street, Yousef Abad
City
Tehran
Province
Tehran
Postal code
1539474621
Phone
+98 21 8810 9722
Email
hganjizadeh@gmail.com
13
Recruitment center
Name of recruitment center
Shohadaye Yaft Abad Hospital
Full name of responsible person
Mitra Najafipour Moghadam
Street address
South Al Ghadir Boulevard, Al Ghadir Square, Moallem Square,