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

NCT03421119 | Unknown Phase 3

• 1 other identifier: LIR.CIN.MK95
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

type 2 diabetes; liraglutide; efficacy; safety

Outcome Measures

Primary Outcomes (1)

• HbA1c

  The primary outcome of this study is to assess changes in HbA1c in both treatment arms

  26 weeks

Secondary Outcomes (11)

• HbA1c < 7.0%

  26 weeks

• HbA1c ≤ 6.5%

  26 weeks

• Body weight

  26 weeks

• Fasting blood sugar

  26 weeks

• Postprandial glucose

  26 weeks

Study Arms (2)

CinnaGen-liraglutide

EXPERIMENTAL

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; Drug: Metformin; Drug: Sulfonylurea/non-sulfonylurea insulin secretagogues

Victoza®

ACTIVE COMPARATOR

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; Drug: Metformin; Drug: Sulfonylurea/non-sulfonylurea insulin secretagogues

Interventions

Liraglutide 6 MG/ML Pen Injector DRUG

Patients in each arm will receive either CinnaGen-liraglutide or Victoza®. Both products will be provided as pen-injector.

Also known as: CinnaGen-liraglutide, Victoza

CinnaGen-liraglutide; Victoza®

Metformin DRUG

Patients who were receiving metformin with maximum tolerable dose prior to study will continue to receive it during the study.

Also known as: Metformin Hydrochloride

CinnaGen-liraglutide; Victoza®

Sulfonylurea/non-sulfonylurea insulin secretagogues DRUG

Patients who were receiving Sulfonylurea/non-sulfonylurea insulin secretagogues with maximum tolerable dose prior to study will continue to receive it during the study.

Also known as: Sulfonylurea or non-sulfonylurea insulin secretagogues

CinnaGen-liraglutide; Victoza®

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age
• ≤ HbA1c \< 10
• Body mass index (BMI) of 25-45 kg / m2

You may not qualify if:

• 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

Sponsors & Collaborators

• Cinnagen: lead

Related Publications (6)

• Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009 Jan;32(1):84-90. doi: 10.2337/dc08-1355. Epub 2008 Oct 17.

  PMID: 18931095 BACKGROUND

• Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S; LEAD-1 SU study group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med. 2009 Mar;26(3):268-78. doi: 10.1111/j.1464-5491.2009.02666.x.

  PMID: 19317822 BACKGROUND

• Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L; LEAD-4 Study Investigators. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care. 2009 Jul;32(7):1224-30. doi: 10.2337/dc08-2124. Epub 2009 Mar 16.

  PMID: 19289857 BACKGROUND

• Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simo R; Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia. 2009 Oct;52(10):2046-55. doi: 10.1007/s00125-009-1472-y. Epub 2009 Aug 14.

  PMID: 19688338 BACKGROUND

• Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L; LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009 Jul 4;374(9683):39-47. doi: 10.1016/S0140-6736(09)60659-0. Epub 2009 Jun 8.

  PMID: 19515413 BACKGROUND

• Esteghamati A, Zamanzadeh M, Malek M, Khaledi M, Monavari A, Najafi L, Banazadeh Z, Malboosbaf R, Aghili R, Mahdikhah S, Ganjizadeh-Zavereh H, Kafi H, Hosseinpanah F, Khamseh ME. Efficacy and Safety of a Biosimilar Liraglutide (Melitide(R)) Versus the Reference Liraglutide (Victoza(R)) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial. Diabetes Ther. 2023 Nov;14(11):1889-1902. doi: 10.1007/s13300-023-01462-w. Epub 2023 Sep 14.

  PMID: 37707701 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Study Officials

• Mohammad Ebrahim Khamseh, Professor

  Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Somayeh Amini, PharmD

CONTACT

00989398079606; amini.s@orchidpharmed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: February 5, 2018
• Study Start: June 20, 2019
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 6, 2019

Record last verified: 2019-02