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

Type 2 Diabetes Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01798706
• Other study ID #: EFC12703
• Secondary ID: 2012-003292-19U1
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2013
• Last updated: February 11, 2016
• Start date: June 2013
• Est. completion date: February 2015

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary objective:

• To evaluate the effect of lixisenatide versus placebo over a period of 24 weeks on glycemic control, as evaluated by HbA1c reduction, in older type 2 diabetes patients (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 patients (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- 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 patients requiring rescue therapy

• Safety and tolerability

• To assess lixisenatide pharmacokinetic profile

• To assess anti-lixisenatide antibody development.

Description:

Approximately 31 weeks including 24 week treatment period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 70 Years and older

Eligibility

Inclusion criteria :

• Older patients, 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 patients and that this is the responsibility of the investigator to include the patient based on an individual evaluation of the expected benefits of better glycemic control versus risk of hypoglycemia)

• At screening patients 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 antidiabetic agent than allowed background therapy. Allowed therapy includes metformin, sulfonylurea [except glibenclamide >10mg, glicazide >160mg], meglitinides [except repaglinide >6mg], pioglitazone and basal insulin and should follow local product circulars and labeling restrictions for the study population. .

• Patients who have been on an approved or an investigational 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/m²

• Malnutrition assessed clinically by the investigator or any sub-investigator and by 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 MMSE score <24 (the judgment of the investigator prevails on questionnaires scores), or any neurologic disorder that will affect the patient's ability to participate in the study

• Patient who have an eGFR (using the Modification of Diet in Renal Disease {MDRD} formula <30ml/min/1.73m2

• Patients 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

• ALT or 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 (ie, worsening) and not controlled (ie, 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 predisposes to medullary thyroid cancer (eg, multiple endocrine neoplasia syndromes)

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• lixisenatide (AVE0010)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• placebo
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• antidiabetic therapy
Background therapy, if given to be continued on a stable dose, may include: Basal insulin, metformin, sulfonylurea (except glibenclamide>10mg, gliclazide>160 mg), meglitinides (except repaglinide> 6mg) and/or pioglitazone.

Locations

Country	Name	City	State
Australia	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
Bulgaria	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
Canada	Investigational Site Number 124003	Hamilton
Canada	Investigational Site Number 124007	London
Canada	Investigational Site Number 124002	Sherbrooke
Canada	Investigational Site Number 124001	St-Romuald
Canada	Investigational Site Number 124005	Vancouver
Canada	Investigational Site Number 124006	Vancouver
Canada	Investigational Site Number 124008	Westmount
Canada	Investigational Site Number 124004	Winnipeg
Denmark	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
Germany	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
Norway	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
Peru	Investigational Site Number 604001	Arequipa
Peru	Investigational Site Number 604002	Lima
Peru	Investigational Site Number 604003	Lima
Peru	Investigational Site Number 604005	Lima
Peru	Investigational Site Number 604006	Lima
Peru	Investigational Site Number 604007	Lima
Peru	Investigational Site Number 604011	Lima
Peru	Investigational Site Number 604008	Piura
Poland	Investigational Site Number 616004	Gdansk
Poland	Investigational Site Number 616003	Krakow
Poland	Investigational Site Number 616001	Poznan
Poland	Investigational Site Number 616002	Ruda Slaska
Poland	Investigational Site Number 616006	Szczecin
South Africa	Investigational Site Number 710002	Cape Town
South Africa	Investigational Site Number 710003	Cape Town
South Africa	Investigational Site Number 710004	Somerset West
Spain	Investigational Site Number 724001	Alcira
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
Sweden	Investigational Site Number 752006	Göteborg
Sweden	Investigational Site Number 752007	Härnösand
Sweden	Investigational Site Number 752002	Lund
Sweden	Investigational Site Number 752004	Malmö
Sweden	Investigational Site Number 752001	Stockholm
Sweden	Investigational Site Number 752003	Stockholm
United Kingdom	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 States	Investigational Site Number 840017	Biloxi	Mississippi
United States	Investigational Site Number 840014	Canal Fulton	Ohio
United States	Investigational Site Number 840002	Des Moines	Iowa
United States	Investigational Site Number 840006	Fargo	North Dakota
United States	Investigational Site Number 840010	La Jolla	California
United States	Investigational Site Number 840003	Miami	Florida
United States	Investigational Site Number 840012	Miami	Florida
United States	Investigational Site Number 840007	Milwaukee	Wisconsin
United States	Investigational Site Number 840015	Norwalk	California
United States	Investigational Site Number 840009	Omaha	Nebraska
United States	Investigational Site Number 840008	Oxon Hill	Maryland
United States	Investigational Site Number 840004	Rockville	Maryland
United States	Investigational Site Number 840016	Salisbury	North Carolina
United States	Investigational Site Number 840011	St. George	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in HbA1c		week 24	No
Secondary	Change from baseline in fasting Plasma Glucose (FPG)		week 24	No
Secondary	Change in 2-hour PPG and plasma glucose excursions (2-hour postprandial plasma glucose - FPG) during the liquid standardized breakfast meal test from baseline		week 24	No
Secondary	Change in 7-point Self-Monitored plasma glucose (SMPG) profile (i.e, the average and each time point of the 7 points) from baseline		week 24	No
Secondary	Change in body weight from baseline		week 24	No
Secondary	Change in total daily basal insulin dose from baseline for patients taking basal insulin		week 24	No
Secondary	Percentage of patients requiring rescue therapy during the 24-week double-blind treatment period		week 24	No
Secondary	Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)		week 24	Yes
Secondary	Severe hypoglycemia		week 24	Yes
Secondary	Gastrointestinal side effects		week 24	Yes