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

NCT02625636 | Completed Phase 1

• 2 other identifiers: TDU14518U1111-1172-1152
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess the tolerability and safety of SAR438544 after single ascending subcutaneous (SC) doses in healthy subjects and in type 1 diabetes mellitus (T1DM) patients. Secondary Objective: To assess the preliminary pharmacodynamics (PD) and pharmacokinetic (PK) parameters of SAR438544 after single ascending SC doses in healthy subjects and in T1DM patients.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  Day 1 to Day 7 (+/- 1 day)

Secondary Outcomes (11)

• Assessment of PD parameter: continuous monitoring of blood glucose levels over a period of 6 hours post-dose

  Day 1

• Assessment of PD parameter: area under plasma concentration of the BG-time curve between investigational medicinal product (IMP) dosing and time t (BG-AUC0-t)

  Day 1

• Assessment of PD parameter: BG-maximum concentration (BG-Cmax)

  Day 1

• Assessment of PD parameter: BG-time to Cmax (BG-tmax)

  Day 1

• Assessment of PK parameter (recombinant glucagon and SAR438544): Cmax

  Day 1

Study Arms (6)

SAR438544 dose 1

EXPERIMENTAL

Single dose of SAR438544 given SC under fasting conditions

Drug: SAR438544

SAR438544 dose 2

EXPERIMENTAL

Single dose of SAR438544 given SC under fasting conditions

Drug: SAR438544

SAR438544 dose 3

EXPERIMENTAL

Single dose of SAR438544 given SC under fasting conditions

Drug: SAR438544

Placebo

PLACEBO COMPARATOR

Single dose of placebo given SC under fasting conditions

Drug: placebo

Glucagon

ACTIVE COMPARATOR

Single dose of glucagon given SC under fasting conditions

Drug: r-glucagon

SAR438544 Optional Dose

EXPERIMENTAL

Optional lower, intermediate, or higher dose of SAR438544 given SC under fasting conditions

Drug: SAR438544

Interventions

SAR438544 DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

SAR438544 Optional Dose; SAR438544 dose 1; SAR438544 dose 2; SAR438544 dose 3

placebo DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Placebo

r-glucagon DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: GlucaGen® HypoKit, glucagon

Glucagon

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 840001

Chula Vista, California, 91911, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 9, 2015
• Study Start: December 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 23, 2016

Record last verified: 2016-08

Locations

US (1)