Comparing Efficacy and Safety of CinnaGen-liraglutide Versus Victoza® in Patients With Type II Diabetes

February 5, 2019 updated by: Cinnagen

A Phase III, Randomized, Parallel, Double-blind, and Non-inferiority Clinical Trial to Compare Efficacy and Safety of CinnaGen-liraglutide to Innovator Liraglutide Product (Victoza®) in Patients With Type II Diabetes (T2D)

The purpose of this study is to compare the efficacy and safety of liraglutide produced by CinnaGen company and Novo Nordisk liraglutide (Victoza®) in subjects with type II diabetes. Patients with Type II diabetes treated with two oral glucose-lowering agents for ≥ 3 months, aged between 30 to 65 years, HbA1c equal or greater than 7.5 and lower than 10, and BMI between 25 to 45 were included in this study.

This study is a phase III, randomized, two-armed, parallel, double-blind, active-controlled, and non-inferiority clinical trial. Patients who enter the trial will be randomly allocated (1:1 ratio) to receive subcutaneous 1.8 mg daily injections of either Victoza® or CinnaGen-liraglutide. Doses of liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks up to 1.8 mg/day from the beginning of the fifth week. Patients continue to receive 1.8 mg/day liraglutide until the end 26th week.

The primary objective of this study is to assess non-inferiority of CinnaGen-liraglutide to reference liraglutide in terms of efficacy in patients with T2D. The secondary objectives of this study are to further compare the efficacy of CinnaGen-liraglutide to reference liraglutide and to assess the safety of CinnaGen-liraglutide to reference liraglutide.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to compare the efficacy and safety of liraglutide produced by CinnaGen company with Novo Nordisk liraglutide (Victoza®) in subjects with type II diabetes. Patients with Type II diabetes treated with two oral glucose-lowering agents for ≥ 3 months, aged between 30 to 65 years, HbA1c equal or greater than 7.5 and lower than 10, and BMI between 25 to 45 will be included in this study. This study is a phase III, randomized, two-armed, parallel, double-blind, active-controlled, and non-inferiority clinical trial. Patients who enter the trial will be randomly allocated (1:1 ratio) to receive subcutaneous 1.8 mg daily injections of either Victoza® or CinnaGen-liraglutide. Doses of liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks up to 1.8 mg/day from the beginning of the fifth week. Patients continue to receive 1.8 mg/day liraglutide until the end of 26th week.

Physical examinations and vital signs will be evaluated for patients at baseline, and at weeks 4, 8, 12 and 26 visits. Laboratory parameters will be assessed at baseline, week 12 and 26. The incidence of adverse events will be evaluated based on patients' reports, vital signs, physical examinations, and laboratory tests.

Before initiation, the trial will be reviewed by food and drug administration of Iran. The protocol, electronic case report form (eCRF), information for patients and informed consent form will be submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.

In this study, no patient will be recruited without informed consent. All the informed consent forms which will be signed by the patients will have two copies so that patients can receive a copy of it.

Determination of sample size:

Group sample sizes of 120 and 120 achieve 80% power to detect non-inferiority using a one-sided, two-sample t-test with a non-inferiority margin of -0.4. The true difference between the means is assumed to be zero. The significance level (alpha) of the test is 0.025. The data are drawn from populations with standard deviations of 1.1 and considering a drop-out rate of 20% total sample size required is 300 patients.

Data Quality Assurance:

CinnaGen Company conducts clinical trials according to procedures that incorporate the ethical principles of GCP. Accurate and reliable data collection is assured by verification and cross-check of the eCRFs against the patient's records by clinical monitors, and the maintenance of a drug-dispensing log by the center.

CRO coordinators and sponsor attend the SIV (Site Initiation Visit) meetings. Protocol and GCP principles will be reviewed by coordinating investigator of each site, and also the needed information for completing eCRF forms will be explained.

Monitoring by CRO is performed in 30% and 70% of study progress and at the end of the study. In the monitoring sessions some sponsor personnel audit the process. During the monitoring process, CRO coordinator checks all eCRFs and confirms them to the source documents, and for required cases, the query form will be filled out.

The temperature of the refrigerator containing the medicines is checked and recorded by data logger which will be monitored regularly by the auditor.

CRO coordinator will verify drug accountability data and information about the proper time for patients' injections, and sponsor staff rechecks it.

After monitoring, problems are reported by monitor and auditor to the trial centers.

Blinding:

In order to prevent the influence of knowing intervention group on study results, the patients and those who assess the study outcomes will remain unaware of allocation to test- or reference-liraglutide.

For this purpose, patients and caregivers will be masked to allocated treatment by making reference and test products indiscernible by appearance. Medicines will be provided in a similar dosage form labeled with a unique code.

It should be noted that CRO personnel who enter data into eCRF and database and also the sponsoring personnel who monitor data entry are blinded. The study is double-blind and situations that might warrant breaking the code are defined in the protocol and include serious adverse events.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with Type 2 diabetes treated with maximum tolerable dose of two oral glucose-lowering agents (OGLAs; Metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues) for ≥ 3 months
  • 30-65 years of age
  • 7.5 ≤ HbA1c < 10
  • Body mass index (BMI) of 25-45 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 ≥ 2·5 times upper normal range).
  • Impaired renal function (eGFR < 60 mL/min/1.73 m2),
  • Uncontrolled hypertension (≥ 160/100 mmHg),
  • Malignancy
  • Used 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
  • 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
  • History or known case of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy
  • Pregnancy
  • Previous exposure to exenatide or liraglutide

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CinnaGen-liraglutide
CinnaGen-liraglutide (Liraglutide 6 MG/ML Pen Injector by CinnaGen Company) will be administered 1.8 mg/day subcutaneously. Doses of CinnaGen-liraglutide will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
Drug: Liraglutide 6 MG/ML Pen Injector
Patients in each arm will receive either CinnaGen-liraglutide or Victoza®. Both products will be provided as pen-injector.
Other Names:
  • CinnaGen-liraglutide, Victoza
Drug: Metformin
Patients who were receiving metformin with maximum tolerable dose prior to study will continue to receive it during the study.
Other Names:
  • Metformin Hydrochloride
Drug: Sulfonylurea/non-sulfonylurea insulin secretagogues
Patients who were receiving Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose prior to study will continue to receive it during the study.
Other Names:
  • Sulfonylurea or non-sulfonylurea insulin secretagogues
Active Comparator: Victoza®
Victoza® (Liraglutide 6 MG/ML Pen Injector by Novo Nordisk Company) will be administered 1.8 mg/day subcutaneously. Doses of Victoza® will be up-titrated from 0.6 mg/day in the first week to 1.2 mg/day in the second, third and fourth weeks, up to 1.8 mg/day from the start of the fifth week to the end of 26th week. Patients in this group will continue to receive metformin along with a Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose.
Drug: Liraglutide 6 MG/ML Pen Injector
Patients in each arm will receive either CinnaGen-liraglutide or Victoza®. Both products will be provided as pen-injector.
Other Names:
  • CinnaGen-liraglutide, Victoza
Drug: Metformin
Patients who were receiving metformin with maximum tolerable dose prior to study will continue to receive it during the study.
Other Names:
  • Metformin Hydrochloride
Drug: Sulfonylurea/non-sulfonylurea insulin secretagogues
Patients who were receiving Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose prior to study will continue to receive it during the study.
Other Names:
  • Sulfonylurea or non-sulfonylurea insulin secretagogues

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HbA1c
Time Frame: 26 weeks
The primary outcome of this study is to assess changes in HbA1c in both treatment arms
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HbA1c < 7.0%
Time Frame: 26 weeks
Percentages of subjects achieving HbA1c < 7.0% is measured in both treatment arms
26 weeks
HbA1c ≤ 6.5%
Time Frame: 26 weeks
Percentages of subjects achieving HbA1c ≤ 6.5% is measured in both treatment arms
26 weeks
Body weight
Time Frame: 26 weeks
Changes in body weight is measured in both treatment arms
26 weeks
Fasting blood sugar
Time Frame: 26 weeks
Changes in FBS is measured in both treatment arms
26 weeks
Postprandial glucose
Time Frame: 26 weeks
Changes in mean PPG is measured in both treatment arms
26 weeks
Systolic blood pressure
Time Frame: 26 weeks
Changes in SBP (mmHg) is measured in both treatment arms
26 weeks
Diastolic blood pressure
Time Frame: 26 weeks
Changes in DBP (mmHg) is measured in both treatment arms
26 weeks
Lipid profiles
Time Frame: 26 weeks
Changes in Lipid profiles is measured in both treatment arms
26 weeks
Pulse Rate
Time Frame: 26 weeks
Changes in PR is measured in both treatment arms
26 weeks
estimated Glomerular Filtration Rate
Time Frame: 26 weeks
Changes in eGFR is measured in both treatment arms
26 weeks
Liver enzymes
Time Frame: 26 weeks
Changes in AST and ALT is measured in both treatment arms
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cinnagen

Investigators

  • Principal Investigator: Mohammad Ebrahim Khamseh, Professor, Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 20, 2019

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

January 29, 2018

First Submitted That Met QC Criteria

January 29, 2018

First Posted (Actual)

February 5, 2018

Study Record Updates

Last Update Posted (Actual)

February 6, 2019

Last Update Submitted That Met QC Criteria

February 5, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LIR.CIN.MK95

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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