Clinical trial NCT02713477: Postprandial Glucodynamic Response to Insulin Glargine/Lixisenatide Fixed Ratio Combination in Japanese Patients With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-03-18
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Measurement of plasma glucose concentrations
timeFrame: 1 day (D1) in each treatment period
Secondary outcomes:
measure: Measurement of serum insulin concentrations
timeFrame: 1 day (D1) in each treatment period
measure: Measurement of serum C-peptide concentrations
timeFrame: 1 day (D1) in each treatment period
measure: Measurement of plasma glucagon concentrations
timeFrame: 1 day (D1) in each treatment period
measure: Measurement of plasma lixisenatide concentrations
timeFrame: 1 day (D1) in each treatment period
measure: Number of patients with hypoglycemic events
timeFrame: Up to 2 weeks after each treatment
measure: Number of patients with adverse events
timeFrame: Up to 2 weeks after each treatment
measure: Measurement of anti-lixisenatide antibodies
timeFrame: 2 days (prior to first dosing and end of study visit)
measure: Measurement of anti-insulin antibodies
timeFrame: 2 days (prior to first dosing and end of study visit)
Other outcomes:
Locations:
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.