Clinical trial NCT01169779: Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin
Official title: Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-07-26
Enrollment: 391
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The study duration for each patient is 27 weeks +/- 10 days (up to 2 weeks screening + 1 week run-in + 24 weeks double-blind treatment + 3 days follow-up).

Eligibility criteria: Inclusion criteria:

- 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

Exclusion criteria:

* 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
* Known history of drug or alcohol abuse within 6 months prior to the time of screening
* Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure (SBP) or diastolic blood pressure (DBP) \>180 millimeter of mercury (mmHg) or \>95 mmHg, respectively
* Laboratory findings at the time of screening: amylase and/or lipase: \>3 times upper limit of normal (ULN); hemoglobin \<11 gram/deciliter and/or neutrophils \<1500 per cubic millimeter (mm\^3) and/or platelets \<100 000/mm\^3; calcitonin \>20 picogram per milliliter (5.9 picomole per liter) ; and positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
* Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, or vital signs at the time of screening that, in the judgment of the investigator or any sub-investigator, precludes safe completion of the study or constrains efficacy assessment
* Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as attending scheduled visits, being able to do self-injections; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
* Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin and sulfonylurea (for example, alpha-glucosidase inhibitor, thiazolidinedione, glucagon-like peptide -1 \[GLP-1\], receptor agonist, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
* Use of any investigational drug within 3 months prior to screening;
* Participation in a previous study with lixisenatide
* Renal impairment defined with creatinine \>1.4 mg/dL in women and creatinine \>1.5 mg/dL in men
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
* Allergic reaction to any GLP-1 agonist in the past (for example, exenatide, liraglutide) or to metacresol
* Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (\>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator

Primary outcomes:
measure: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Weight at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
timeFrame: Week 24
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
timeFrame: Week 24
measure: Change From Baseline in Glucose Excursion at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
timeFrame: Baseline up to Week 24
Other outcomes:
measure: Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration
Locations:
city: Beijing
country: China
facility: Investigational Site Number 156011
city: Beijing
country: China
facility: Investigational Site Number 156012
city: Beijing
country: China
facility: Investigational Site Number 156019
city: Beijing
country: China
facility: Investigational Site Number 156002
city: Beijing
country: China
facility: Investigational Site Number 156003
city: Beijing
country: China
facility: Investigational Site Number 156009
city: Beijing
country: China
facility: Investigational Site Number 156001
city: Changchun
country: China
facility: Investigational Site Number 156036
city: Changsha
country: China
facility: Investigational Site Number 156016
city: Changsha
country: China
facility: Investigational Site Number 156015
city: Chengdu
country: China
facility: Investigational Site Number 156006
city: Chengdu
country: China
facility: Investigational Site Number 156032
city: Dalian
country: China
facility: Investigational Site Number 156010
city: Guangzhou
country: China
facility: Investigational Site Number 156004
city: Guangzhou
country: China
facility: Investigational Site Number 156008
city: Guangzhou
country: China
facility: Investigational Site Number 156025
city: Haikou
country: China
facility: Investigational Site Number 156031
city: Harbin
country: China
facility: Investigational Site Number 156014
city: Hefei
country: China
facility: Investigational Site Number 156029
city: Qingdao
country: China
facility: Investigational Site Number 156013
city: Shanghai
country: China
facility: Investigational Site Number 156007
city: Shanghai
country: China
facility: Investigational Site Number 156030
city: Shenyang
country: China
facility: Investigational Site Number 156020
city: Suzhou
country: China
facility: Investigational Site Number 156035
city: Taiyuan
country: China
facility: Investigational Site Number 156033
city: Tianjin
country: China
facility: Investigational Site Number 156037
city: Xi'An
country: China
facility: Investigational Site Number 156022
city: Xi'An
country: China
facility: Investigational Site Number 156023
city: Hong Kong
country: Hong Kong
facility: Investigational Site Number 344001
city: Hong Kong
country: Hong Kong
facility: Investigational Site Number 344003
city: Shatin, Nt
country: Hong Kong
facility: Investigational Site Number 344002
city: Kelantan
country: Malaysia
facility: Investigational Site Number 458001
city: Kuala Lumpur
country: Malaysia
facility: Investigational Site Number 458003
city: Putrajaya
country: Malaysia
facility: Investigational Site Number 458002
city: Bangkok
country: Thailand
facility: Investigational Site Number 764002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.