Protocol summary
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Study aim
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Comparing the efficacy and safety of Cinnagen liraglutide and Novo Nordisk Victoza® in type II diabetes patients
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Design
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randomized, two-armed, parallel, double-blind, active-controlled, non-inferiority clinical trial of 300 type II diabetes patients
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Settings and conduct
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2 cities (Tehran and Karaj) and 17centers 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.
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Participants/Inclusion and exclusion criteria
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Subjects with type 2 diabetes treated for ≥3 months with a stable metformin dose of ≥1500mg and at least half the maximum dose of a insulin secretagogues agent; 18–80years old; 7≤HbA1c≤10.5; 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 MEN syndrome type 2; History of pancreatic cancer and pancreatitis; Recent MI; Pregnancy or Previous exposure to exenatide or liraglutide.
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Intervention groups
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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
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Main outcome variables
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Change in HbA1c after 26 weeks of treatment
General information
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Reason for update
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Protocol changes:Blood test and antidrug antibody presence evaluating (week 0 week 12 and week 26)
HbA1c equal or greater than 7 and equal or smaller than 10.5
18–80years of age
Subjects with type 2 diabetes treated for ≥ 3 months with a stable metformin dose of ≥1500 mg and at least half the maximum dose of a sulfonylurea or non-sulfonylurea insulin secretagogues agent(Half of maximum dose)
breast-feeding Female who intends to become pregnant during the clinical trial period
Dr. Mahsan Seifoddin-Melli Bank Hospital
Dr. Mohammad Khaledi- Lolagar Hospital
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20150303021315N15
Registration date:
2019-09-13, 1398/06/22
Registration timing:
registered_while_recruiting
Last update:
2020-09-29, 1399/07/08
Update count:
3
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Registration date
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2019-09-13, 1398/06/22
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2019-06-10, 1398/03/20
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Expected recruitment end date
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2021-05-02, 1400/02/12
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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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)
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Public title
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Comparing Efficacy and Safety of CinnaGen-liraglutide Versus Victoza® in Patients with Type II Diabetes
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Subjects with type 2 diabetes treated for ≥ 3 months with a stable metformin dose of ≥1500 mg and at least half the maximum dose of a sulfonylurea or non-sulfonylurea insulin secretagogues agent(Half of maximum dose)
18–80years of age
HbA1c equal or greater than 7 and equal or smaller than 10.5
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).
Current use of a dipeptidyl peptidase-4 inhibitor (DPP-4i)
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, uncontrolled CHF, and unstable Angina within last 3 months
History or known case of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy
Pregnancy or breast-feeding
Female who intends to become pregnant during the clinical trial period
Previous exposure to exenatide or liraglutide.
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Age
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From 18 years old to 80 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
300
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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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.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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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, The center researcher and the patient are not aware of the drug grouping.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Secondary Ids
1
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Registry name
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ClinicalTrial.gov
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Secondary trial Id
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NCT03421119
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Registration date
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2018-02-02, 1396/11/13
Ethics committees
1
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Ethics committee
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Approval date
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2019-01-23, 1397/11/03
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Ethics committee reference number
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IR.IUMS.REC.1396.31731
2
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Ethics committee
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Approval date
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2019-06-15, 1398/03/25
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Ethics committee reference number
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IR.ABZUMS.REC.1398.052
Health conditions studied
1
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Description of health condition studied
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type 2 diabetes
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ICD-10 code
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E11
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ICD-10 code description
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Type 2 diabetes mellitus
Primary outcomes
1
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Description
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Change in HbA1c after 26 weeks of treatment
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Timepoint
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Screening, baseline, week 12, and week 26
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Method of measurement
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By High-performance liquid chromatography (HPLC)
Secondary outcomes
1
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Description
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Percentages of subjects achieving HbA1c < 7.0%
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Timepoint
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Screening, baseline, week 12, and week 26
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Method of measurement
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-By High-performance liquid chromatography(HPLC)
2
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Description
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Percentages of subjects achieving HbA1c ≤ 6.5%
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Timepoint
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Screening, baseline week 12, and week 26
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Method of measurement
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By High-performance liquid chromatography(HPLC)
3
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Description
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Changes in body weight
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Timepoint
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Screening, baseline week 12, and week 26
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Method of measurement
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Scales
4
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Description
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Changes in mean FBS
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Timepoint
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Baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
5
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Description
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Changes in mean PPBS
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Timepoint
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Baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
6
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Description
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Changes in Systolic Blood Pressure
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Timepoint
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Screening, baseline, week 4, week 8, week 12, and week 26
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Method of measurement
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Medical examination
7
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Description
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Changes in Diastolic Blood Pressure
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Timepoint
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Screening, baseline, week 4, week 8, week 12, and week 26
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Method of measurement
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Medical examination
8
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Description
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Changes in Lipid profiles
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Timepoint
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Baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
9
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Description
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Change in Pulse Rate
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Timepoint
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Screening, baseline, week 4, week 8, week 12, and week 26
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Method of measurement
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Medical examination
10
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Description
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Change in eGFR
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Timepoint
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Screening, baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
11
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Description
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Change in ALT
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Timepoint
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Screening, Baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
12
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Description
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Change in liver AST
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Timepoint
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Baseline, week 12, and week 26
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Method of measurement
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Laboratory Test
13
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Description
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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
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Timepoint
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Screening, baseline, week 4, week 8, week 12, week 16, week 20, and week 26
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Method of measurement
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evaluation adverse events and adverse drug reaction
14
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Description
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Change in quality of life
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Timepoint
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Baseline, week 12 and week 26
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Method of measurement
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EQ5D questionnaire
15
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Description
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Medication adherence
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Timepoint
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Baseline, week 12 and week 26
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Method of measurement
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Morisky questionnaire
16
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Description
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Cost-effectiveness
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Timepoint
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Baseline, week 4, week 8, week 12, week 16, week 20 and week 26
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Method of measurement
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Cost-effectiveness questionnaire
17
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Description
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Fear of injection
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Timepoint
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Baseline, week 12 and week 26
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Method of measurement
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D-FISQ questionnaire
Intervention groups
1
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Description
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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.
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Category
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Treatment - Drugs
2
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Description
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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.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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CinnaGen Company
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available