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Efficacy and Safety of Lixisenatide Versus Placebo on Top of Basal Insulin and/or Oral Antidiabetic Treatment in Older Type 2 Diabetic Patients (GetGoal-O)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01798706
First received: February 22, 2013
Last updated: October 14, 2016
Last verified: October 2016
  Purpose

Primary objective:

- To evaluate the effect of lixisenatide versus placebo over a period of 24 weeks on glycemic control, as evaluated by glycosylated hemoglobin (HbA1c) reduction, in older type 2 diabetes participants (T2DM) who are inadequately controlled with their current anti-diabetic treatment regimen.

Main secondary objective:

- To assess the safety and tolerability of lixisenatide compared to placebo in older T2DM participants (including occurrence of documented (Plasma Glucose PG < 60 mg/dL) symptomatic hypoglycemia and gastrointestinal side effects).

Other secondary objectives:

  • To assess the effect of lixisenatide compared to placebo after 24-week treatment on:

    • Fasting plasma glucose (FPG);
    • During liquid standardized breakfast meal challenge test : 2 hour- Postprandial Plasma Glucose (PPG) and Plasma Glucose Excursion;
    • 7-point Self-monitored plasma glucose (SMPG) profile;
    • Body weight;
    • Change in total daily dose of basal insulin (if taken);
    • Percentage of participants requiring rescue therapy
    • Safety and tolerability;
  • To assess lixisenatide pharmacokinetic profile;
  • To assess anti-lixisenatide antibody development.

Condition Intervention Phase
Type 2 Diabetes
Drug: Lixisenatide (AVE0010)
Drug: Placebo
Drug: Antidiabetic background therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter, 24 Week Study Assessing the Safety and Efficacy of Lixisenatide in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Diabetes Treatment Regimen

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Absolute Change in HbA1c From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed=participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.


Secondary Outcome Measures:
  • Change in 2-Hour PPG From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.

  • Change in Average 7-point SMPG Profiles From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug.

  • Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.

  • Change in FPG From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug.

  • Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
    Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) 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 after Week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >270 mg/dL (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >9%.

  • Change in Plasma Glucose Excursions From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Plasma glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the liquid standardized breakfast meal test, before study drug administration. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.

  • Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy) [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Change in basal insulin dose was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.

  • Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia [ Time Frame: First dose of study drug up to 3 days after the last dose administration (maximum of 171 days) ] [ Designated as safety issue: Yes ]
    Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.

  • Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug.

  • Percentage of Participants With Gastrointestinal Disorders [ Time Frame: Up to Day 171 ] [ Designated as safety issue: Yes ]

Enrollment: 350
Study Start Date: June 2013
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lixisenatide
Lixisenatide 10 mcg once daily (QD) for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg.
Drug: Lixisenatide (AVE0010)

Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning

Route of administration: Subcutaneous injection

Other Name: Lyxumia
Drug: Antidiabetic background therapy
Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide >10 mg, gliclazide >160 mg), meglitinides (except repaglinide >6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin.
Placebo Comparator: Placebo
Placebo (matched to lixisenatide) QD for 24 Weeks.
Drug: Placebo

Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning

Route of administration: Subcutaneous injection

Drug: Antidiabetic background therapy
Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide >10 mg, gliclazide >160 mg), meglitinides (except repaglinide >6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin.

Detailed Description:
Approximately 31 weeks including 24 week treatment period.
  Eligibility

Ages Eligible for Study:   70 Years and older   (Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Older participants, aged 70 years and above, with T2DM inadequately controlled on their current anti-diabetic pharmaceutical treatment regimen.
  • Signed written informed consent.

Exclusion criteria:

  • At screening HbA1c ≤7.0% or >10% (Acknowledging that the threshold of 7% may not be appropriate for all older participants and that this was the responsibility of the investigator to include the participant based on an individual evaluation of the expected benefits of better glycemic control versus risk of hypoglycemia).
  • At screening participants on both basal insulin and sulfonylurea or basal insulin and meglitinides.
  • At screening FPG >250 mg/dL (>13.9 mmol/L).
  • Type 1 diabetes mellitus or history of ketoacidosis within one year prior to the screening visit.
  • Type 2 diabetes mellitus diagnosed less than 1 year prior to screening.
  • Anti-diabetic treatment not at a stable regimen or initiated within the last 3 months prior to screening.
  • Treatment within the 3 months preceding the screening with other anti-diabetic agent than allowed background therapy. Allowed therapy includes metformin, sulfonylurea (except glibenclamide >10mg, gliclazide >160mg), meglitinides (except repaglinide >6mg), pioglitazone and basal insulin and should follow local product circulars and labeling restrictions for the study population.
  • Participants who had been on an approved or an investigational Glucagon-like peptide 1 (GLP-1) medication (exenatide, liraglutide, lixisenatide or others).
  • History of severe hypoglycemia associated with symptoms unawareness or results in unconsciousness/coma/seizure in the 6 months prior to screening.
  • BMI <22 or >40 kg/m^2.
  • Malnutrition assessed clinically by the investigator or any sub-investigator and by Mini-Nutritional Assessment-Short Form (MNA-SF) score <12 in countries (the judgment of the investigator prevails on questionnaires scores).
  • Cognitive disorder and dementia assessed clinically by the investigator or any sub investigator and by Mini Mental State Examination (MMSE) score <24 (the judgment of the investigator prevails on questionnaires scores), or any neurologic disorder that affected the participant's ability to participate in the study.
  • Participant who had a glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease (MDRD) formula <30ml/min/1.73m^2).
  • Participant with severe or uncontrolled disease, or any clinically significant abnormality identified on physical examination or investigational clinical procedure that, in the judgment of the investigator or any sub-investigator, would preclude safe completion of the study or constrains efficacy assessment.
  • Laboratory findings at the time of screening:

    • Amylase and/or lipase: >3 times the upper limit of the normal (ULN) laboratory range
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times ULN
    • Calcitonin >20 pg/mL (5.9 pmol/L).
  • Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e. worsening) and not controlled (i.e. prolonged nausea and vomiting) gastroesophageal reflux disease within 6 months prior to screening.
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease.
  • Personal or immediate family history of medullary thyroid cancer or genetic conditions that predisposed to medullary thyroid cancer (e.g., multiple endocrine neoplasia syndromes).

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01798706

  Hide Study Locations
Locations
United States, California
Investigational Site Number 840010
La Jolla, California, United States, 92037
Investigational Site Number 840015
Norwalk, California, United States, 90650
United States, Florida
Investigational Site Number 840003
Miami, Florida, United States, 33156
Investigational Site Number 840012
Miami, Florida, United States, 33156
United States, Iowa
Investigational Site Number 840002
Des Moines, Iowa, United States, 50314
United States, Maryland
Investigational Site Number 840008
Oxon Hill, Maryland, United States, 20745
Investigational Site Number 840004
Rockville, Maryland, United States, 20852
United States, Mississippi
Investigational Site Number 840017
Biloxi, Mississippi, United States, 39531
United States, Nebraska
Investigational Site Number 840009
Omaha, Nebraska, United States, 68131
United States, North Carolina
Investigational Site Number 840016
Salisbury, North Carolina, United States, 28144
United States, North Dakota
Investigational Site Number 840006
Fargo, North Dakota, United States, 58103
United States, Ohio
Investigational Site Number 840014
Canal Fulton, Ohio, United States, 44614
United States, Utah
Investigational Site Number 840011
St. George, Utah, United States, 84790
United States, Wisconsin
Investigational Site Number 840007
Milwaukee, Wisconsin, United States, 53209
Australia
Investigational Site Number 036002
Box Hill, Australia, 3128
Investigational Site Number 036006
Brookvale, Australia, 2100
Investigational Site Number 036004
Camperdown, Australia, 2050
Investigational Site Number 036005
Gosford, Australia, 2250
Investigational Site Number 036001
Heidelberg, Australia, 3081
Investigational Site Number 036003
Parkville, Australia, 3050
Bulgaria
Investigational Site Number 100002
Plovdiv, Bulgaria, 4002
Investigational Site Number 100005
Plovdiv, Bulgaria, 4002
Investigational Site Number 100003
Sofia, Bulgaria, 1632
Investigational Site Number 100004
Stara Zagora, Bulgaria, 6000
Investigational Site Number 100001
Varna, Bulgaria, 9000
Canada
Investigational Site Number 124003
Hamilton, Canada, L8L 5G8
Investigational Site Number 124007
London, Canada, N6B 2E3
Investigational Site Number 124002
Sherbrooke, Canada, J1H 5N4
Investigational Site Number 124001
St-Romuald, Canada, G6W 5M6
Investigational Site Number 124005
Vancouver, Canada, V5Z 1M9
Investigational Site Number 124006
Vancouver, Canada, V5Z 1M9
Investigational Site Number 124008
Westmount, Canada, H3Z 1E5
Investigational Site Number 124004
Winnipeg, Canada, R3E 3P4
Denmark
Investigational Site Number 208005
Esbjerg, Denmark, 6700
Investigational Site Number 208001
København Nv, Denmark, 2400
Investigational Site Number 208004
København S, Denmark, 2300
Investigational Site Number 208002
Slagelse, Denmark, 4200
Investigational Site Number 208003
Svendborg, Denmark, 5700
Germany
Investigational Site Number 276005
Dresden, Germany, 01307
Investigational Site Number 276004
Essen, Germany, 45359
Investigational Site Number 276002
München, Germany, 80639
Investigational Site Number 276001
Münster, Germany, 48145
Investigational Site Number 276006
Pirna, Germany, 01796
Investigational Site Number 276007
Pohlheim, Germany, 35415
Investigational Site Number 276008
Potsdam, Germany, 14469
Investigational Site Number 276003
Saarlouis, Germany, 66740
Norway
Investigational Site Number 578001
Hønefoss, Norway, 3515
Investigational Site Number 578005
Kongsvinger, Norway, 2212
Investigational Site Number 578003
Oslo, Norway
Investigational Site Number 578006
Stavanger, Norway, 4095
Investigational Site Number 578004
Trondheim, Norway, 7012
Peru
Investigational Site Number 604001
Arequipa, Peru
Investigational Site Number 604011
Lima, Peru, 27
Investigational Site Number 604005
Lima, Peru, LIMA 10
Investigational Site Number 604003
Lima, Peru, LIMA 14
Investigational Site Number 604006
Lima, Peru, LIMA 31
Investigational Site Number 604002
Lima, Peru
Investigational Site Number 604007
Lima, Peru
Investigational Site Number 604008
Piura, Peru
Poland
Investigational Site Number 616004
Gdansk, Poland, 80-858
Investigational Site Number 616003
Krakow, Poland, 31-024
Investigational Site Number 616001
Poznan, Poland, 61-665
Investigational Site Number 616002
Ruda Slaska, Poland, 41-709
Investigational Site Number 616006
Szczecin, Poland, 70-506
South Africa
Investigational Site Number 710003
Cape Town, South Africa, 7500
Investigational Site Number 710002
Cape Town, South Africa, 7530
Investigational Site Number 710004
Somerset West, South Africa, 7130
Spain
Investigational Site Number 724001
Alcira, Spain, 46600
Investigational Site Number 724005
Barcelona, Spain, 08035
Investigational Site Number 724006
Hostalets De Balenyà, Spain, 08550
Investigational Site Number 724003
Madrid, Spain, 28046
Investigational Site Number 724002
Sanlúcar De Barrameda, Spain, 11540
Investigational Site Number 724004
Santiago De Compostela, Spain, 15706
Sweden
Investigational Site Number 752006
Göteborg, Sweden, 405 45
Investigational Site Number 752007
Härnösand, Sweden, 871 82
Investigational Site Number 752002
Lund, Sweden, 22221
Investigational Site Number 752004
Malmö, Sweden, 211 52
Investigational Site Number 752003
Stockholm, Sweden, 111 57
Investigational Site Number 752001
Stockholm, Sweden, 171 76
United Kingdom
Investigational Site Number 826003
Bexhill-On-Sea, United Kingdom, TN39 4SP
Investigational Site Number 826001
Glasgow, United Kingdom
Investigational Site Number 826002
Irvine, United Kingdom, KA12 0AY
Investigational Site Number 826004
Trowbridge, United Kingdom, BA14 8QA
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01798706     History of Changes
Other Study ID Numbers: EFC12703  2012-003292-19  U1111-1132-9156 
Study First Received: February 22, 2013
Results First Received: August 22, 2016
Last Updated: October 14, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 09, 2016