Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin

NCT01169779 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC11321U1111-1116-8938
• Study Type: interventional
• Target: 391
• Locations: 4 countries
• Sites: 35

Brief Summary

The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010) in comparison to placebo, as an add-on treatment to metformin with or without sulfonylurea, over a period of 24 weeks of treatment. The primary objective is to assess the effects on glycemic control of lixisenatide (AVE0010) in comparison to placebo as an add-on treatment to metformin with or without sulfonylurea in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. The secondary objectives are to assess the effects of lixisenatide over 24 weeks on percentage of patients reaching HbA1c less than (\< ) 7 percent (%) or HbA1c less than or equal to (\<=) 6.5%, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and glucose excursion during standardized meal test, body weight; to evaluate safety, tolerability, pharmacokinetic (PK) and anti-lixisenatide antibody development.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24

  Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.

  Baseline, Week 24

Secondary Outcomes (7)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

  Baseline, Week 24

• Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24

  Baseline, Week 24

• Change From Baseline in Body Weight at Week 24

  Baseline, Week 24

• Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24

  Week 24

• Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24

  Week 24

Other Outcomes (2)

• Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24

  Baseline, Week 24

• Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia

  First dose of study drug up to 3 days after the last dose administration

Study Arms (2)

Lixisenatide

EXPERIMENTAL

1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24.

Drug: Lixisenatide (AVE0010); Device: Pen auto-injector; Drug: Metformin; Drug: Sulfonylurea

Placebo

PLACEBO COMPARATOR

1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24.

Drug: Placebo; Device: Pen auto-injector; Drug: Metformin; Drug: Sulfonylurea

Interventions

Lixisenatide (AVE0010) DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Lixisenatide

Placebo DRUG

Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Placebo

Pen auto-injector DEVICE

Also known as: OptiClik®

Lixisenatide; Placebo

Metformin DRUG

Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.

Lixisenatide; Placebo

Sulfonylurea DRUG

Sulfonylurea if given at screening, to be continued up to Week 24. In patients with a screening HbA1c \<8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values. In patients with a screening HbA1c \>=8%, the dose is not to be changed at randomization. In any case, after Week 12, sulfonylurea is to be continued at a stable dose.

Lixisenatide; Placebo

Eligibility Criteria

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

You may qualify if:

• \- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin alone or metformin with sulfonylurea at the time of the screening visit

You may not qualify if:

• HbA1c \<7% or greater than (\>) 10% at screening
• At the time of screening age \< legal age of majority
• Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
• Type 1 diabetes mellitus
• Treatment with metformin not at a stable dose of at least 1.0 gram per day or more than 1.5 gram per day for at least 3 months prior to screening visit
• In case of treatment with sulfonylurea, if the sulfonylurea dosage is less than the maximum effective dose (that is, half of the maximum recommended dose according to local labeling), or is not at a stable (unchanged) dose for at least 3 months prior to screening
• FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
• History of hypoglycemia unawareness
• Body mass index \<=20 kilogram per square meter (kg/m\^2)
• Weight change of \>5 kg during the 3 months preceding the screening visit
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease or patients considered by the investigator at high risk for acute pancreatitis (for example, with known history of biliary gallstone\[s\], or with very high triglyceride level \[\>=5.65 mmol/L\]) at the time of screening
• Personal or family history of medullary thyroid cancer or genetic conditions that predispose to medullary thyroid cancer (for example, multiple endocrine neoplasia syndromes);
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization

Sponsors & Collaborators

• Sanofi: lead

Study Sites (35)

Investigational Site Number 156011

Beijing, 100034, China

Location

Investigational Site Number 156012

Beijing, 100101, China

Location

Investigational Site Number 156019

Beijing, 100191, China

Location

Investigational Site Number 156002

Beijing, 100700, China

Location

Investigational Site Number 156003

Beijing, 100730, China

Location

Investigational Site Number 156009

Beijing, 100730, China

Location

Investigational Site Number 156001

Beijing, 100853, China

Location

Investigational Site Number 156036

Changchun, 130041, China

Location

Investigational Site Number 156016

Changsha, 410008, China

Location

Investigational Site Number 156015

Changsha, 410011, China

Location

Investigational Site Number 156006

Chengdu, 610041, China

Location

Investigational Site Number 156032

Chengdu, 610072, China

Location

Investigational Site Number 156010

Dalian, 116027, China

Location

Investigational Site Number 156004

Guangzhou, 510080, China

Location

Investigational Site Number 156008

Guangzhou, 510080, China

Location

Investigational Site Number 156025

Guangzhou, 510630, China

Location

Investigational Site Number 156031

Haikou, 57028, China

Location

Investigational Site Number 156014

Harbin, 150001, China

Location

Investigational Site Number 156029

Hefei, 230022, China

Location

Investigational Site Number 156013

Qingdao, 266003, China

Location

Investigational Site Number 156007

Shanghai, 200003, China

Location

Investigational Site Number 156030

Shanghai, 200065, China

Location

Investigational Site Number 156020

Shenyang, 110004, China

Location

Investigational Site Number 156035

Suzhou, 215004, China

Location

Investigational Site Number 156033

Taiyuan, 030001, China

Location

Investigational Site Number 156037

Tianjin, 300052, China

Location

Investigational Site Number 156022

Xi'an, 710032, China

Location

Investigational Site Number 156023

Xi'an, 710061, China

Location

Investigational Site Number 344001

Hong Kong, Hong Kong

Location

Investigational Site Number 344003

Hong Kong, Hong Kong

Location

Investigational Site Number 344002

Shatin, Nt, Hong Kong

Location

Investigational Site Number 458001

Kelantan, 16150, Malaysia

Location

Investigational Site Number 458003

Kuala Lumpur, 59100, Malaysia

Location

Investigational Site Number 458002

Putrajaya, 62250, Malaysia

Location

Investigational Site Number 764002

Bangkok, 10400, Thailand

Location

Related Publications (2)

• Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, Lv X, Tian H, Jin Kui Y, Su B, Shang S, Niemoeller E. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014 Nov;30(8):726-35. doi: 10.1002/dmrr.2541.

  PMID: 24639432 RESULT

• Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.

  PMID: 27252787 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-us@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 23, 2010
• First Posted: July 26, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 13, 2016
• Results First Posted: October 13, 2016

Record last verified: 2016-08

Locations

MY (3); TH (1); HK (3); CN (28)