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Trial · Interventional

CompletedPhase 3Results postedRegistry data

24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine

Short name GetGoal-Duo1

NCTNCT00975286 (opens ClinicalTrials.gov in a new tab)Other idEFC10781Other idEudraCT : 2008-007335-40

Overview

Status
Completed
Phase
Phase 3
Enrollment
446 participants (actual)
Sponsor
Sanofi · Industry
Design
Randomized · Double masking
Countries
26 countries

United States, Argentina, Brazil, Canada, Chile, Colombia, Czechia, Denmark, Estonia, France, Germany, Hungary, India, Israel, Italy, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russia, South Africa, Sweden, Taiwan, Ukraine

Start
Oct 2009
Primary completion
Aug 2011
Completion
Aug 2011
First posted
11 Sept 2009 (estimated)
Last update posted
11 Oct 2016 (estimated)
Conditions
Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2009201020112012
  1. Ph 3

    GetGoal-Duo1

    NCT00975286

    Oct 2009 to Aug 2011

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidinediones (TZDs), over a period of 24 weeks of treatment. The primary objective is to assess the effects of lixisenatide in comparison to placebo, when added to insulin glargine and metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. The secondary objectives are to assess the effects of lixisenatide on the percentage of patients reaching HbA1c less than (\<) 7 percent (%) and less than or equal to (\<=) 6.5%, plasma glucose (fasting, postprandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses, to evaluate safety and tolerability (including anti-lixisenatide antibody assessment), and to assess the impact on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated.

Interventions

  • Lixisenatide (AVE0010)Drug
  • PlaceboDrug
  • Insulin glargineDrug
  • Pen auto-injectorDevice
  • MetforminDrug
  • Thiazolidinedione (TZD)Drug

Arms2

  • Experimental

    Lixisenatide

    2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.

  • Placebo comparator

    Placebo

    2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.

Primary outcomes1

Outcomes the sponsor listed as primary.

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

    Time frame · Baseline, Week 24

    Registry description

    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 14 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 assessment for at least 1 efficacy variable, were required.

Secondary outcomes(10)
  1. Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24

    Time frame · Baseline, Week 24

    Registry description

    The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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 assessment for at least 1 efficacy variable, were required.

  2. Change From Baseline in Glucose Excursion at Week 24

    Time frame · Baseline, Week 24

    Registry description

    Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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 assessment for at least 1 efficacy variable, were required.

  3. Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24

    Time frame · Baseline, Week 24

    Registry description

    Patients recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime once in a week and the average value for the 7-time points was calculated. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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 assessment for at least 1 efficacy variable, were required.

  4. Change From Baseline in Body Weight at Week 24

    Time frame · Baseline, Week 24

    Registry description

    Change was calculated by subtracting baseline value from Week 24 value. 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 assessment for at least 1 efficacy variable, were required.

  5. Change From Baseline in Average Insulin Glargine Daily Dose at Week 24

    Time frame · Baseline, Week 24

    Registry description

    Change was calculated by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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 assessment for at least 1 efficacy variable, were required.

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

    Time frame · Baseline, Week 24

    Registry description

    Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day 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 assessment for at least 1 efficacy variable, were required.

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

    Time frame · Week 24

    Registry description

    The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 14 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 assessment for at least 1 efficacy variable, were required.

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

    Time frame · Week 24

    Registry description

    The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 14 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 assessment for at least 1 efficacy variable, were required.

  9. Percentage of Patients Requiring Rescue Therapy During the Double-blind Period

    Time frame · Baseline up to Week 24

    Registry description

    Routine fasting SMPG, central laboratory FPG and HbA1c values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG and HbA1c were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>200 milligram/deciliter (mg/dL) (11.1 mmol/L) or HbA1c \>9%, from Week 8 to Week 24: fasting SMPG/FPG \>180 mg/dL (10.0 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

  10. Change From Baseline in Treatment Satisfaction Score (Sum of Items 1, 4, 5, 6, 7 and 8 of DTSQ) at Week 24

    Time frame · Baseline, Week 24

    Registry description

    Change was calculated by subtracting baseline value from Week 24 value. DTSQ: 8-item questionnaire to assess treatment satisfaction and patient perception of hyper and hypoglycemia. Each question (Q) scored on a Likert scale from 0 to 6. Six items (Q1 and 4-8; higher score = more satisfaction) measured treatment satisfaction and were summed to calculate treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied). Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively and lower scores represented good perceived blood glucose control. 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 assessment for at least 1 efficacy variable, were required.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 24

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

GroupValue (percentage of hemoglobin)Spread
Placebo-0.400.092
Lixisenatide-0.710.091
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 24

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

GroupValue (mmol/L)Spread
Placebo0.080.481
Lixisenatide-3.090.482
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Glucose Excursion at Week 24

GroupValue (mmol/L)Spread
Placebo-0.330.461
Lixisenatide-3.420.462
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24

GroupValue (mmol/L)Spread
Placebo-0.080.179
Lixisenatide-0.470.178
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Body Weight at Week 24

GroupValue (kilogram)Spread
Placebo1.160.330
Lixisenatide0.280.331
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Average Insulin Glargine Daily Dose at Week 24

GroupValue (units per day)Spread
Placebo5.341.256
Lixisenatide3.101.260
Secondary outcomeLeast squares mean· Baseline, Week 24

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

GroupValue (mmol/L)Spread
Placebo0.460.214
Lixisenatide0.340.213
Other pre specified outcomeNumber· Baseline, Week 24

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

GroupValue (percentage of participants)
Placebo3.2
Lixisenatide5.1

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Placebo2-step initiation regimen of volume matching placebo.–10 / 22381 / 223
Lixisenatide2-step initiation regimen of lixisenatide.–17 / 223127 / 223

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies6

Studies that cite this trial.

Studies with results

4 studies on this page

PubMed tag: none · 2023

2 results

Impact of Type 2 Diabetes Duration on the Efficacy and Safety of Add-on Lixisenatide in Asian Individuals Receiving Basal Insulin: A Pooled Analysis.

Yao et al. 2023Diabetes therapy : research, treatment and education of diabetes and related disorders

PMID 36809495PMC10064411DOI 10.1007/s13300-023-01369-6PUB-36809495

Free to read · publisher termsCC BY-NC2 results

PubMed tag: none · 2020

2 results

Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data.

Davidson et al. 2020Clinical diabetes and endocrinologycited by 5

PMID 31956422PMC6961286DOI 10.1186/s40842-019-0088-5PUB-31956422

CC BY2 results

Indexing hint: Randomized controlled trial · 2013

7 results

Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1).

Riddle et al. 2013Diabetes carecited by 217

PMID 23564915PMC3747901DOI 10.2337/dc12-2462PUB-23564915

Free to read · publisher termsCC BY-NC-ND7 results

Indexing hint: Randomized controlled trial · 2013

10 results

Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L).

Riddle et al. 2013Diabetes carecited by 239

PMID 23628617PMC3747925DOI 10.2337/dc12-2454PUB-23628617

Free to read · publisher termsCC BY-NC-ND10 results

More studies

2 studies on this page

Indexing hint: Observational study · 2018

Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes.

Rosenstock et al. 2018Diabetes, obesity & metabolismcited by 14

PMID 29974618PMC6282993DOI 10.1111/dom.13462PUB-29974618

Free to read · publisher termsCC BY-NC-ND
Read at source

Indexing hint: Meta-analysis (pooled) · 2014

Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis.

Charbonnel et al. 2014Journal of diabetes and its complicationscited by 39

PMID 25130920DOI 10.1016/j.jdiacomp.2014.07.007PUB-25130920

Full text at the publisher
Publisher page

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria: \- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with insulin glargine and metformin 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 * Metformin not at a stable dose of at least 1.5 gram per day for at least 3 months prior to the screening visit * Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea (SU) and TZDs (for example, alpha glucosidase inhibitor, other glucagon like peptide-1 \[GLP-1\] receptor agonists, dipeptidyl peptidase-IV \[DPP-IV\] inhibitors, insulin etc.) within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit * History of hypoglycemia unawareness * Body Mass Index (BMI) less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2) * History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes) * History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening * Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion 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 * 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 such as active malignant tumor or other major systemic diseases, presence of clinically significant diabetic retinopathy 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 or diastolic blood pressure \>180 millimeter of mercury (mmHg) or \>110 mmHg, respectively * Laboratory findings at the time of screening: amylase and/or lipase, alanine aminotransferase \>3 times upper limit of the normal (ULN) laboratory range; total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter and/or neutrophils \<1500 per cubic millimeter (mm\^3) and/or platelets \<100 000/mm\^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody, positive serum pregnancy test in females of childbearing potential; and calcitonin \>=20 picogram per milliliter (pg/mL) (5.9 picomole per milliliter \[pmol/L\]) * 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 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, patient being investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol etc.) * Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening * Use of any investigational drug within 3 months prior to screening * Renal impairment defined with serum creatinine \> 1.4 mg/dL in women and \> 1.5 mg/dL in men * History of hypersensitivity to insulin glargine or to any of the excipients * 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 * Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide) * Allergic reaction to any GLP-1 receptor agonist in the past (for example, exenatide, liraglutide) or to metacresol * Additional exclusion criteria during or at the end of the run-in phase before randomization: informed consent withdrawal (patient who was not willing to continue or failed to return), mean fasting SMPG calculated from the self-measurements for the 7 days prior to Visit 12 (Week -1) was \>140 mg/dL (7.8 mmol/L) and HbA1c measured at Visit 12 (Week -1) is \<7% or \>9%, amylase and/or lipase \> 3 times the ULN at Visit 12 (Week -1), patients with fasting plasma glucose (FPG) above the threshold value described for rescue (that is, FPG \>240 mg/dL \[13.3 mmol/L\]), patients with any adverse event, which, by the judgment of the Investigator precludes the inclusion in the double-blind randomized treatment phase, and lack of compliance to protocol or to insulin glargine treatment during the run-in phase

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