A Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Doses of SAR438544 in Comparison to Placebo and Glucagon in Healthy Subjects and Type 1 Diabetes Mellitus Patients

Healthy subjects:

The total duration of study per subject is up to 4.5 weeks with 2 to 21 days screening
period, 1 day for treatment, and 7 days (+/- 1 day) follow-up after IMP administration.

T1DM patients:

The total duration of study per patient is up to 5.5 weeks with 3 to 28 days screening
period, 1 day for treatment, and 7 days (+/- 1 day) follow-up after IMP administration.

One or more interim analyses may be performed to support decisions for the next steps of the
study.

Inclusion criteria :

Healthy subjects:

- Male or female subjects, between 18 and 45 years of age, inclusive.

- Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0
kg, inclusive, if female, body mass index (BMI) between 18.0 and 30.0 kg/m^2,
inclusive.

- Certified as healthy by a comprehensive clinical assessment (detailed medical history
and complete physical examination).

- Female subject must use a double contraception method, including a highly effective
method of birth control, except if she has undergone sterilization defined as tubal
occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and
bilateral tubal ligation at least 3 months earlier or is postmenopausal.

- The accepted double contraception methods include the use of intrauterine device or
hormonal contraception started at least 30 days prior to the screening start and
continued for at least 3 months after IMP dosing in addition to one of the following
contraceptive options: (1) condom plus spermicide; (2) diaphragm plus spermicide or
cervical/vault cap plus spermicide. Menopause is defined as being amenorrheic for at
least 2 years with plasma FSH level >30 UI/L in women older than 40 years of age

- Having given written informed consent prior to undertaking any study-related
procedure.

- Not under any administrative or legal supervision.

- Male subject, whose partners are of childbearing potential (including lactating
women), must accept to use, during sexual intercourse, a double contraception method
according to the following algorithm: (condom, diaphragm or cervical cap, plus
spermicide) plus (intra-uterine device or hormonal contraceptive) from the inclusion
up to 3 months after the last dosing (except if sterilized).

- Male subject, whose partners are pregnant, must use, during sexual intercourse, a
condom from the inclusion up to 3 months after the last dosing.

- Male subject has agreed not to donate sperm from the inclusion up to 3 months after
the last dosing.

T1DM patients:

- Male or female patients, between 18 and 60 years of age, inclusive, with T1DM for at
least one year, as defined by the American Diabetes Association.

- Total (basal+short acting) daily insulin dose of <1.2 U/kg/day.

- Body weight between 50.0 and 110 kg, inclusive, the BMI between 18.5 and 30.0 kg/m^2,
inclusive.

- Fasting serum C-peptide <0.3 nmol/L.

- Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9%).

- Stable insulin regimen for at least 2 months prior to study and self-monitoring of
blood glucose before screening visit.

- Certified as otherwise healthy for T1DM by assessment of medical history and physical
examination (cardiovascular system, chest and lungs, thyroid, abdomen, nervous
system, skin and mucosae, and musculoskeletal system), unless the Investigator
considers any abnormality to be clinically irrelevant and not interfering with the
conduct of the study.

- Female subject must use a double contraception method, including a highly effective
method of birth control, except if she has undergone sterilization defined as tubal
occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and
bilateral tubal ligation at least 3 months earlier or is postmenopausal.

- The accepted double contraception methods include the use of intrauterine device or
hormonal contraception started at least 30 days prior to the screening start and
continued for at least 3 months after IMP dosing in addition to one of the following
contraceptive options: (1) condom plus spermicide; (2) diaphragm plus spermicide or
cervical/vault cap plus spermicide. Menopause is defined as being amenorrheic for at
least 2 years with plasma FSH level >30 UI/L in women older than 40 years of age.

- Having given written informed consent prior to undertaking any study-related
procedure.

- Not under any administrative or legal supervision.

- Male subject, whose partners are of childbearing potential (including lactating
women), must accept to use, during sexual intercourse, a double contraception method
according to the following algorithm: (condom, diaphragm or cervical cap, plus
spermicide) plus (intra-uterine device or hormonal contraceptive) from the inclusion
up to 3 months after the last dosing (except if sterilized).

- Male subject, whose partners are pregnant, must use, during sexual intercourse, a
condom from the inclusion up to 3 months after the last dosing.

- Male subject has agreed not to donate sperm from the inclusion up to 3 months after
the last dosing.

Exclusion criteria:

Healthy subjects:

- 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.

- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice
a month).

- Blood donation, any volume, within 2 months before inclusion.

- 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 any drug allergy or allergic disease that in the opinion of
the Investigator may interfere with subject safety or data integrity during the
study.

- History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per
day on a regular basis).

- Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during
the study.

- If female, pregnancy (defined as positive beta-human chorionic gonadotropin [β-HCG]
blood test), breast-feeding.

- Any medication (including St John's Wort) within 14 days before inclusion or within 5
times the elimination half-life or PD half-life of the medication, with the exception
of hormonal contraception or menopausal hormone replacement therapy; any vaccination
within the last 28 days and any biologics (antibody or its derivatives) given within
4 months before inclusion.

- Any subject who, in the judgment of the Investigator, is likely to be noncompliant
during the study, or unable to cooperate because of a language problem or poor mental
development.

- Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen,
anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and
2 antibodies (anti-HIV1 and anti HIV2 Ab) and human immunodeficiency virus 1 antigen
(HIV1 Ag).

- Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine, opiates).

- Positive alcohol breath test.

T1DM patients:

- Any history or presence of clinically relevant cardiovascular (includes ischemia,
atrioventricular [AV] block; arrhythmias), pulmonary, gastrointestinal, hepatic,
renal, metabolic (apart from diabetes mellitus type 1), hematological, neurological,
osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or
infectious disease, or signs of acute illness.

- 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 severe headaches and/or migraine, recurrent nausea and/or vomiting (more
than twice a month).

- Blood loss (>300 mL) within 3 months before inclusion.

- 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 any drug allergy or allergic disease that in the opinion of
the Investigator may interfere with patient safety or data integrity during the
study.

- 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 at
screening and before any treatment periods (defined as positive β-HCG urine test).

- Any patient who, in the judgment of the Investigator, is likely to be noncompliant
during the study, or unable to cooperate because of a language problem or poor mental
development.

- Positive result on any of the following tests: HBs Ag, anti-HCV Abs, anti-HIV1 and
anti-HIV2 Abs and HIV1 Ag.

- Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine, opiates).

- Positive alcohol breath test.

- Known hypersensitivity to glucagon, lactose or any other constituent in GlucaGen^®
HypoKit and SAR438544 and their excipients.

- Any contraindication from the use of glucagon:

- Pheochromocytoma

- Insulinoma and glucagonoma

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