A Bioequivalence Study Comparing Two Different Strengths Formulations of Insulin Lispro in Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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Primary Objective: To demonstrate bioequivalence between insulin lispro given as SAR342434, 200 Units/ml test formulation (T) and insulin lispro 100 Units/ml reference formulation (R) after a single subcutaneous (SC) dose Secondary Objectives: To assess the pharmacodynamic profiles and further pharmacokinetic characteristics of the test formulation (T) in comparison to the reference formulation (R) after a single SC dose To assess the safety and tolerability of the test and the reference formulation of insulin lispro

Detailed Description
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Study duration per participant is approximately 62 days including a screening period up to 28 days before first dose, 2 periods of 2 days, a wash out period of 5 to 18 days (preferred7 days) and an end of study visit 7 to 14 days after the last dose

Official Title
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A Randomized, Double-blind, Single-dose, 2-treatment, 2-period, 2-sequence Crossover Bioequivalence Study Comparing Two Different Strengths Formulations of Insulin Lispro Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Insulin Lispro SAR342434
* Drug: Insulin Lispro SAR342434


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or female patients, between 18 and 64 years of age, inclusive, with diabetes mellitus type 1 for more than one year Total insulin dose of <1.0 U/kg/day Fasting serum C-peptide <0.30 nmol/L at screening Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9%) at screening Stable insulin regimen for at least 2 months prior to study (day of insulin regimen switch, with respect to safety of the patient and scientific integrity of the study). Patients with anti-insulin antibody titer at screening ≤ 30.0 kU/L Body weight between 50.0 kg and 100.0 kg, inclusive, il male , and between 40.0 and 90.0 kg, inclusive, if female, Body Mass Index between 18 and 30.0 kg/m², inclusive Exclusion criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness or any history or presence of HIT-type II (heparin induced thrombocytopenia Type II) More than 1 episode of severe hypoglycemia resulting in coma/seizures or requiring assistance of another person, and/or hospitalization for diabetic ketoacidosis in the last 6 months before screening visit. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only, more than twice a month). Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20 mmHg within 3 minutes when changing from supine to standing position. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol If female, pregnancy (defined as positive β-HCG blood test), breast-feeding The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test (T)<br>Insulin Lispro (SAR342434), 200 Units/ml, single dose on day 1 of each period | Drug: Insulin Lispro SAR342434<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|
| Active Comparator: Reference (R)<br>Insulin Lispro Sanofi® ,100 Units/ml, single dose on day 1 of each period | Drug: Insulin Lispro SAR342434<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>* Other names: Insulin lispro Sanofi®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of pharmacokinetc (PK) parameter:INS-Cmax | Maximum Insulin (INS) concentration | 10 hours | 
| Assessment of PK parameter :INS-AUClast - | Area under INS concentration time curve from 0 to last measurable concentration - | 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter:INS-AUC | Area under INS concentration time curve from 0 to infinity | 10 hours | 
| Assessment of PK parameter:INS-tmax | Time to reach INS-Cmax | 10 hours | 
| Assessment of PK parameter:INS-t1/2z | INS terminal half life | 10 hours | 
| Assessment of pharmacodynamic (PD) parameter:GIR-AUC0-8 | Area under the Glucose Infusion Rate (GIR) time curve from 0 to 8 hours | 8 hours | 
| Assessment of PD parameter:GIR-max | Maximum smoothed GIR | 8 hours | 
| Assessment of PD parameter:GIR-tmax | Time to reach GIR-max | 8 hours | 
| Duration of blood glucose control | Duration of blood glucose control at or below 105 mg/dL | 8 hours | 
| Adverse Events | Number of participants with adverse events | Up to Day 62 |