Clinical trial NCT01798706: Efficacy and Safety of Lixisenatide Versus Placebo on Top of Basal Insulin and/or Oral Antidiabetic Treatment in Older Type 2 Diabetic Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-02-26
Enrollment: 350
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Approximately 31 weeks including 24 week treatment period.

Eligibility 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.

Primary outcomes:
measure: Absolute Change in HbA1c From Baseline to Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change in 2-Hour PPG From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Average 7-point SMPG Profiles From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in FPG From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period
timeFrame: Baseline up to Week 24
measure: Change in Plasma Glucose Excursions From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy)
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration (maximum of 171 days)
measure: Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia
timeFrame: Week 24
measure: Percentage of Participants With Gastrointestinal Disorders
timeFrame: Up to Day 171
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Investigational Site Number 840010
state: California
city: Norwalk
country: United States
facility: Investigational Site Number 840015
state: California
city: Miami
country: United States
facility: Investigational Site Number 840003
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840012
state: Florida
city: Des Moines
country: United States
facility: Investigational Site Number 840002
state: Iowa
city: Oxon Hill
country: United States
facility: Investigational Site Number 840008
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840004
state: Maryland
city: Biloxi
country: United States
facility: Investigational Site Number 840017
state: Mississippi
city: Omaha
country: United States
facility: Investigational Site Number 840009
state: Nebraska
city: Salisbury
country: United States
facility: Investigational Site Number 840016
state: North Carolina
city: Fargo
country: United States
facility: Investigational Site Number 840006
state: North Dakota
city: Canal Fulton
country: United States
facility: Investigational Site Number 840014
state: Ohio
city: St. George
country: United States
facility: Investigational Site Number 840011
state: Utah
city: Milwaukee
country: United States
facility: Investigational Site Number 840007
state: Wisconsin
city: Box Hill
country: Australia
facility: Investigational Site Number 036002
city: Brookvale
country: Australia
facility: Investigational Site Number 036006
city: Camperdown
country: Australia
facility: Investigational Site Number 036004
city: Gosford
country: Australia
facility: Investigational Site Number 036005
city: Heidelberg
country: Australia
facility: Investigational Site Number 036001
city: Parkville
country: Australia
facility: Investigational Site Number 036003
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 100002
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 100005
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100003
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 100004
city: Varna
country: Bulgaria
facility: Investigational Site Number 100001
city: Hamilton
country: Canada
facility: Investigational Site Number 124003
city: London
country: Canada
facility: Investigational Site Number 124007
city: Sherbrooke
country: Canada
facility: Investigational Site Number 124002
city: St-Romuald
country: Canada
facility: Investigational Site Number 124001
city: Vancouver
country: Canada
facility: Investigational Site Number 124005
city: Vancouver
country: Canada
facility: Investigational Site Number 124006
city: Westmount
country: Canada
facility: Investigational Site Number 124008
city: Winnipeg
country: Canada
facility: Investigational Site Number 124004
city: Esbjerg
country: Denmark
facility: Investigational Site Number 208005
city: København Nv
country: Denmark
facility: Investigational Site Number 208001
city: København S
country: Denmark
facility: Investigational Site Number 208004
city: Slagelse
country: Denmark
facility: Investigational Site Number 208002
city: Svendborg
country: Denmark
facility: Investigational Site Number 208003
city: Dresden
country: Germany
facility: Investigational Site Number 276005
city: Essen
country: Germany
facility: Investigational Site Number 276004
city: München
country: Germany
facility: Investigational Site Number 276002
city: Münster
country: Germany
facility: Investigational Site Number 276001
city: Pirna
country: Germany
facility: Investigational Site Number 276006
city: Pohlheim
country: Germany
facility: Investigational Site Number 276007
city: Potsdam
country: Germany
facility: Investigational Site Number 276008
city: Saarlouis
country: Germany
facility: Investigational Site Number 276003
city: Hønefoss
country: Norway
facility: Investigational Site Number 578001
city: Kongsvinger
country: Norway
facility: Investigational Site Number 578005
city: Oslo
country: Norway
facility: Investigational Site Number 578003
city: Stavanger
country: Norway
facility: Investigational Site Number 578006
city: Trondheim
country: Norway
facility: Investigational Site Number 578004
city: Arequipa
country: Peru
facility: Investigational Site Number 604001
city: Lima
country: Peru
facility: Investigational Site Number 604011
city: Lima
country: Peru
facility: Investigational Site Number 604005
city: Lima
country: Peru
facility: Investigational Site Number 604003
city: Lima
country: Peru
facility: Investigational Site Number 604006
city: Lima
country: Peru
facility: Investigational Site Number 604002
city: Lima
country: Peru
facility: Investigational Site Number 604007
city: Piura
country: Peru
facility: Investigational Site Number 604008
city: Gdansk
country: Poland
facility: Investigational Site Number 616004
city: Krakow
country: Poland
facility: Investigational Site Number 616003
city: Poznan
country: Poland
facility: Investigational Site Number 616001
city: Ruda Slaska
country: Poland
facility: Investigational Site Number 616002
city: Szczecin
country: Poland
facility: Investigational Site Number 616006
city: Cape Town
country: South Africa
facility: Investigational Site Number 710003
city: Cape Town
country: South Africa
facility: Investigational Site Number 710002
city: Somerset West
country: South Africa
facility: Investigational Site Number 710004
city: Alcira
country: Spain
facility: Investigational Site Number 724001
city: Barcelona
country: Spain
facility: Investigational Site Number 724005
city: Hostalets De Balenyà
country: Spain
facility: Investigational Site Number 724006
city: Madrid
country: Spain
facility: Investigational Site Number 724003
city: Sanlúcar De Barrameda
country: Spain
facility: Investigational Site Number 724002
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724004
city: Göteborg
country: Sweden
facility: Investigational Site Number 752006
city: Härnösand
country: Sweden
facility: Investigational Site Number 752007
city: Lund
country: Sweden
facility: Investigational Site Number 752002
city: Malmö
country: Sweden
facility: Investigational Site Number 752004
city: Stockholm
country: Sweden
facility: Investigational Site Number 752003
city: Stockholm
country: Sweden
facility: Investigational Site Number 752001
city: Bexhill-On-Sea
country: United Kingdom
facility: Investigational Site Number 826003
city: Glasgow
country: United Kingdom
facility: Investigational Site Number 826001
city: Irvine
country: United Kingdom
facility: Investigational Site Number 826002
city: Trowbridge
country: United Kingdom
facility: Investigational Site Number 826004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Meneilly GS, Roy-Duval C, Alawi H, Dailey G, Bellido D, Trescoli C, Manrique Hurtado H, Guo H, Pilorget V, Perfetti R, Simpson H; GetGoal-O Trial Investigators. Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial. Diabetes Care. 2017 Apr;40(4):485-493. doi: 10.2337/dc16-2143. Epub 2017 Feb 10.