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

NCT ID: NCT01798706

Last Updated: 2017-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2015-02-28

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Lixisenatide (AVE0010)

Intervention Type: DRUG

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

Route of administration: Subcutaneous injection

Antidiabetic background therapy

Intervention Type: DRUG

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

Placebo (matched to lixisenatide) QD for 24 Weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Route of administration: Subcutaneous injection

Antidiabetic background therapy

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Lyxumia

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.

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840010

La Jolla, California, United States

Investigational Site Number 840015

Norwalk, California, United States

Investigational Site Number 840003

Miami, Florida, United States

Investigational Site Number 840012

Miami, Florida, United States

Investigational Site Number 840002

Des Moines, Iowa, United States

Investigational Site Number 840008

Oxon Hill, Maryland, United States

Investigational Site Number 840004

Rockville, Maryland, United States

Investigational Site Number 840017

Biloxi, Mississippi, United States

Investigational Site Number 840009

Omaha, Nebraska, United States

Investigational Site Number 840016

Salisbury, North Carolina, United States

Investigational Site Number 840006

Fargo, North Dakota, United States

Investigational Site Number 840014

Canal Fulton, Ohio, United States

Investigational Site Number 840011

St. George, Utah, United States

Investigational Site Number 840007

Milwaukee, Wisconsin, United States

Investigational Site Number 036002

Box Hill, , Australia

Investigational Site Number 036006

Brookvale, , Australia

Investigational Site Number 036004

Camperdown, , Australia

Investigational Site Number 036005

Gosford, , Australia

Investigational Site Number 036001

Heidelberg, , Australia

Investigational Site Number 036003

Parkville, , Australia

Investigational Site Number 100002

Plovdiv, , Bulgaria

Investigational Site Number 100005

Plovdiv, , Bulgaria

Investigational Site Number 100003

Sofia, , Bulgaria

Investigational Site Number 100004

Stara Zagora, , Bulgaria

Investigational Site Number 100001

Varna, , Bulgaria

Investigational Site Number 124003

Hamilton, , Canada

Investigational Site Number 124007

London, , Canada

Investigational Site Number 124001

Saint Romuald, , Canada

Investigational Site Number 124002

Sherbrooke, , Canada

Investigational Site Number 124005

Vancouver, , Canada

Investigational Site Number 124006

Vancouver, , Canada

Investigational Site Number 124008

Westmount, , Canada

Investigational Site Number 124004

Winnipeg, , Canada

Investigational Site Number 208005

Esbjerg, , Denmark

Investigational Site Number 208001

København NV, , Denmark

Investigational Site Number 208004

København S, , Denmark

Investigational Site Number 208002

Slagelse, , Denmark

Investigational Site Number 208003

Svendborg, , Denmark

Investigational Site Number 276005

Dresden, , Germany

Investigational Site Number 276004

Essen, , Germany

Investigational Site Number 276002

München, , Germany

Investigational Site Number 276001

Münster, , Germany

Investigational Site Number 276006

Pirna, , Germany

Investigational Site Number 276007

Pohlheim, , Germany

Investigational Site Number 276008

Potsdam, , Germany

Investigational Site Number 276003

Saarlouis, , Germany

Investigational Site Number 578001

Hønefoss, , Norway

Investigational Site Number 578005

Kongsvinger, , Norway

Investigational Site Number 578003

Oslo, , Norway

Investigational Site Number 578006

Stavanger, , Norway

Investigational Site Number 578004

Trondheim, , Norway

Investigational Site Number 604001

Arequipa, , Peru

Investigational Site Number 604011

Lima, , Peru

Investigational Site Number 604005

Lima, , Peru

Investigational Site Number 604003

Lima, , Peru

Investigational Site Number 604006

Lima, , Peru

Investigational Site Number 604002

Lima, , Peru

Investigational Site Number 604007

Lima, , Peru

Investigational Site Number 604008

Piura, , Peru

Investigational Site Number 616004

Gdansk, , Poland

Investigational Site Number 616003

Krakow, , Poland

Investigational Site Number 616001

Poznan, , Poland

Investigational Site Number 616002

Ruda Śląska, , Poland

Investigational Site Number 616006

Szczecin, , Poland

Investigational Site Number 710003

Cape Town, , South Africa

Investigational Site Number 710002

Cape Town, , South Africa

Investigational Site Number 710004

Somerset West, , South Africa

Investigational Site Number 724001

Alzira, , Spain

Investigational Site Number 724005

Barcelona, , Spain

Investigational Site Number 724006

Hostalets de Balenyà, , Spain

Investigational Site Number 724003

Madrid, , Spain

Investigational Site Number 724002

Sanlúcar de Barrameda, , Spain

Investigational Site Number 724004

Santiago de Compostela, , Spain

Investigational Site Number 752006

Gothenburg, , Sweden

Investigational Site Number 752007

Härnösand, , Sweden

Investigational Site Number 752002

Lund, , Sweden

Investigational Site Number 752004

Malmo, , Sweden

Investigational Site Number 752003

Stockholm, , Sweden

Investigational Site Number 752001

Stockholm, , Sweden

Investigational Site Number 826003

Bexhill-on-Sea, , United Kingdom

Investigational Site Number 826001

Glasgow, , United Kingdom

Investigational Site Number 826002

Irvine, , United Kingdom

Investigational Site Number 826004

Trowbridge, , United Kingdom

Countries

United States; Australia; Bulgaria; Canada; Denmark; Germany; Norway; Peru; Poland; South Africa; Spain; Sweden; United Kingdom

References

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.

Reference Type: RESULT

PMID: 28188240 (View on PubMed)

Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

Reference Type: DERIVED

PMID: 39963952 (View on PubMed)

Other Identifiers

2012-003292-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1132-9156

Identifier Type: OTHER

Identifier Source: secondary_id

EFC12703

Identifier Type: -

Identifier Source: org_study_id