Multiple Ascending Dose Study in Healthy Male Subjects and Overweight to Obese Male and Female Type 2 Diabetes Mellitus (T2DM) Patients

NCT02411825 | Completed Phase 1

• 3 other identifiers: TDR137002014-004216-10U1111-1163-1209
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess in healthy adult male subjects:

• The tolerability and safety of 21-day repeated subcutaneous (SC) doses of SAR425899 including two up titration steps.
• Pharmacokinetic (PK) parameters of SAR425899 after ascending repeated SC doses in plasma.
• Pharmacodynamic (PD) effects on fasting and postprandial plasma glucose, insulin, biomarkers of lipid metabolism and fibroblast growth factor 21 (FGF21). To assess in overweight to obese T2DM mellitus patients:
• The tolerability and safety after 28-day repeated SC doses of SAR425899 including 2 up titration steps.
• PK parameters of SAR425899 after ascending repeated SC doses in plasma and urine.
• PD effects on fasting and postprandial plasma glucose, insulin, C-peptide, incretin panel (total and active ghrelin, total peptide YY \[PYY\], total and active glucagon-like peptide -1 \[GLP-1\], glucagon and total gastric inhibitory polypeptide-1 \[GIP\]), body weight, FGF21, biomarkers of lipid metabolism and HbA1c.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Number of adverse events

  28 to 35 days

Secondary Outcomes (20)

• Changes in vital signs

  28 to 35 days

• Changes in physical examination

  28 to 35 days

• Changes in ECG

  28 to 35 days

• Changes in clinical laboratory parameters (hematology)

  28 to 35 days

• Changes in clinical laboratory parameters (biochemistry)

  28 to 35 days

Study Arms (4)

SAR425899 (healthy subjects)

EXPERIMENTAL

Once daily SC doses of SAR425899

Drug: SAR425899

Placebo (healthy subjects)

PLACEBO COMPARATOR

Once daily SC doses of placebo

Drug: placebo

SAR425899 (T2DM Patients)

EXPERIMENTAL

Once daily SC doses of SAR425899 and two up titration steps in each dose cohort with metformin as background therapy

Drug: SAR425899; Drug: metformin

Placebo (T2DM Patients)

PLACEBO COMPARATOR

Once daily SC doses of placebo and two up titration steps in each dose cohort with metformin as background therapy

Drug: placebo; Drug: metformin

Interventions

SAR425899 DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

SAR425899 (T2DM Patients); SAR425899 (healthy subjects)

placebo DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo (T2DM Patients); Placebo (healthy subjects)

metformin DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo (T2DM Patients); SAR425899 (T2DM Patients)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects:
• Males, between 18 and 55 years of age, inclusive.
• Body mass index (BMI) between 20.0 and 30.0 kg/m\^2, inclusive; body weight between 50.0 and 120.0 kg, inclusive.
• Certified as healthy by comprehensive clinical assessment (detailed medical history, complete physical examination). Comorbidities of higher weight (eg, mild impaired glucose tolerance, mild hypertension, mild hyperlipidemia) are permitted unless, per investigator, these conditions hamper participation.
• Normal vital signs after 10 minutes resting supine:
• mmHg \<systolic blood pressure (SBP) \<150 mmHg.
• mmHg \<diastolic blood pressure (DBP) \<100 mmHg.
• bpm \<heart rate (HR) \<100 bpm.
• Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position within; 120 ms \<PR \<220 ms, QRS \<120 ms, QTc ≤430 ms, normal ECG.
• Normal 24-hour Holter electrocardiography at screening.
• Laboratory parameters within normal range; however serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase), and total bilirubin (unless subject has Gilbert syndrome) should not exceed upper laboratory norm (ULN).
• T2DM patients:
• Males and females, 18-70 years of age.
• Body weight 50.0-150.0 kg, BMI 28.0 - 42.0 kg/m\^2.
• Normal vital signs supine:

You may not qualify if:

• Healthy subjects:
• History of clinically relevant disease/signs of acute illness.
• History of drug hypersensitivity/allergic disease.
• Smoking more than 5 cigarettes/day.
• T2DM patients:
• History/presence of clinically relevant disease/signs of acute illness not related to patient's metabolic status.
• History/presence of drug hypersensitivity or allergic disease.
• Smoking more than 5 cigarettes per day.
• If female, pregnancy/breast-feeding.
• Any intake of medication during treatment period and within 21 days before first dosing or within 5 times half-life of the medication, except: metformin, standard antihypertensive treatment, statins, acetyl salicylic acid.
• Thyroid hormone replacement is allowed if dose was stable for 3 months prior to screening.
• Individual background therapy, considered necessary for the patient's welfare, that could not be discontinued for the duration of the study, may be given at the discretion of the Investigator, with a stable dose (when possible) and only if its intake is unlikely to interfere with the investigational product.
• Treated with sulphonyl-ureas up to 3 months, proton pump inhibitors up to 1 week prior to dosing.
• Severe hypoglycemia resulting in seizure/unconsciousness/coma/hospitalization for diabetic ketoacidosis in last 3 months before screening.
• Persistent hyperglycemia not controlled by metformin/diet/exercise.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 276001

Berlin, 10117, Germany

Location

Related Publications (2)

• Visentin R, Schiavon M, Gobel B, Riz M, Cobelli C, Klabunde T, Dalla Man C. Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes. Diabetes Obes Metab. 2020 Apr;22(4):640-647. doi: 10.1111/dom.13939. Epub 2019 Dec 22.

  PMID: 31808298 DERIVED

• Tillner J, Posch MG, Wagner F, Teichert L, Hijazi Y, Einig C, Keil S, Haack T, Wagner M, Bossart M, Larsen PJ. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. Diabetes Obes Metab. 2019 Jan;21(1):120-128. doi: 10.1111/dom.13494. Epub 2018 Sep 16.

  PMID: 30091218 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

SAR425899; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: April 8, 2015
• Study Start: March 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 15, 2018

Record last verified: 2018-06

Locations

DE (1)