Postprandial Glucodynamic Response to Insulin Glargine/Lixisenatide Fixed Ratio Combination in Japanese Patients With Type 2 Diabetes Mellitus

A Randomized, Open Label, Placebo-controlled, 4-sequence, 4-period, 4-treatment Crossover Study to Investigate the Postprandial Glucodynamic Response to Single Dose of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Japanese Patients With Type 2 Diabetes Mellitus

Primary Objective:

To assess the postprandial glucodynamic response to 2 doses of insulin glargine/lixisenatide fixed-ratio combination compared to placebo in Japanese patients with type 2 diabetes mellitus (T2DM).

Secondary Objectives:

• To assess the pharmacokinetics (PK) of lixisenatide following administration of 2 different doses of insulin glargine/lixisenatide fixed-ratio combination in Japanese patients with T2DM.
• To assess the postprandial glucodynamic response to insulin glargine/lixisenatide fixed-ratio combination compared to insulin glargine alone in Japanese patients with T2DM.
• To assess the safety and tolerability of insulin glargine/lixisenatide fixed-ratio combination in Japanese patients with T2DM.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010; Drug: Insulin glargine HOE901

Detailed Description

The total study duration per patient will be approximately 6 to 13 weeks that will consist of a 2-28 days of screening period, a 3-day treatment period, a 7-14 days of washout period, and 1-day end of study visit.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-Shi, Japan
    • Investigational Site Number 392001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Japanese male or female patients with T2DM diagnosed for at least 1 year prior to the time of screening as established in the medical history.
• Patients aged 20 to 75 years at screening.
• Body mass index ≤35 kg/m^2 at screening.
• Glycohemoglobin ≥7.0% and ≤10.0% at screening.
• Fasting C-peptide ≥0.6 ng/mL at screening.

Exclusion criteria:

• Diabetes other than T2DM.
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening.
• History of hypoglycemia unawareness.
• Hemoglobinopathy or hemolytic anemia.
• History of myocardial infarction, stroke, or heart failure, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease.
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment.
• Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes).
• If female, pregnancy or breast-feeding.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin glargine/ lixisenatide dose 1 Test 1; Test 1 will be administered thru subcutaneous (SC) injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition	Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010; Pharmaceutical form: solution Route of administration: subcutaneous
Experimental: Insulin glargine/ lixisenatide dose 2 Test 2; Test 2 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition	Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010; Pharmaceutical form: solution Route of administration: subcutaneous
Placebo Comparator: Placebo - Reference 1; Reference 1 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition	Drug: Placebo; Pharmaceutical form: solution Route of administration: subcutaneous
Other: Insulin glargine (Lantus) - Reference 2; Reference 2 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour pior to breakfast under fasted condition	Drug: Insulin glargine HOE901; Pharmaceutical form: solution Route of administration: subcutaneous; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measurement of plasma glucose concentrations	1 day (D1) in each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Measurement of serum insulin concentrations	1 day (D1) in each treatment period
Measurement of serum C-peptide concentrations	1 day (D1) in each treatment period
Measurement of plasma glucagon concentrations	1 day (D1) in each treatment period
Measurement of plasma lixisenatide concentrations	1 day (D1) in each treatment period
Number of patients with hypoglycemic events	Up to 2 weeks after each treatment
Number of patients with adverse events	Up to 2 weeks after each treatment
Measurement of anti-lixisenatide antibodies	2 days (prior to first dosing and end of study visit)
Measurement of anti-insulin antibodies	2 days (prior to first dosing and end of study visit)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Inoue M, Lorenz M, Muto H, Wesch R, Hashimoto Y. Effect of a single dose of insulin glargine/lixisenatide fixed ratio combination (iGlarLixi) on postprandial glucodynamic response in Japanese patients with type 2 diabetes mellitus: A phase I randomized trial. Diabetes Obes Metab. 2019 Aug;21(8):2001-2005. doi: 10.1111/dom.13757. Epub 2019 May 24.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: March 15, 2016
• First Submitted That Met QC Criteria: March 15, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Lixisenatide
• Other Study ID Numbers: PDY14115; U1111-1176-6235 (Other Identifier: UTN)