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

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ClinicalTrials.gov Identifier: NCT02411825
Recruitment Status : Completed
First Posted : April 8, 2015
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE March 24, 2015
First Posted Date  ICMJE April 8, 2015
Last Update Posted Date June 15, 2018
Study Start Date  ICMJE March 2015
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
Number of adverse events [ Time Frame: 28 to 35 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2015)
  • Changes in vital signs [ Time Frame: 28 to 35 days ]
  • Changes in physical examination [ Time Frame: 28 to 35 days ]
  • Changes in ECG [ Time Frame: 28 to 35 days ]
  • Changes in clinical laboratory parameters (hematology) [ Time Frame: 28 to 35 days ]
  • Changes in clinical laboratory parameters (biochemistry) [ Time Frame: 28 to 35 days ]
  • Changes in body temperature [ Time Frame: 28 to 35 days ]
  • Change from baseline in biomarkers (FGF21) [ Time Frame: 28 to 35 days ]
  • Change from baseline in biomarkers (lipid biomarker) [ Time Frame: 28 to 35 days ]
  • Change from baseline in biomarkers (incretins) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (AUC) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (Cmax) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (t1/2) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in urine (Ae0-24) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in urine (fe0-24) [ Time Frame: 28 to 35 days ]
  • Change from baseline in Body weight [ Time Frame: 28 to 35 days ]
  • Change from baseline in Fasting Blood Glucose [ Time Frame: 28 to 35 days ]
  • Change from baseline in Postprandial Blood Glucose [ Time Frame: 28 to 35 days ]
  • Change from baseline in postprandial Insulin [ Time Frame: 28 to 35 days ]
  • Change from baseline in postprandial C-peptide profiles [ Time Frame: 28 to 35 days ]
  • Change from baseline in HbA1c [ Time Frame: 28 to 35 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
  • Changes in vital signs [ Time Frame: 28 to 35 days ]
  • Changes in physical examination [ Time Frame: 28 to 35 days ]
  • Changes in ECG [ Time Frame: 28 to 35 days ]
  • Changes in clinical laboratory parameters (hematology) [ Time Frame: 28 to 35 days ]
  • Changes in clinical laboratory parameters (biochemistry) [ Time Frame: 28 to 35 days ]
  • Changes in body temperature [ Time Frame: 28 to 35 days ]
  • Change from baseline in biomarkers (FGF21) [ Time Frame: 28 to 35 days ]
  • Change from baseline in biomarkers (lipid biomarker) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (AUC) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (Cmax) [ Time Frame: 28 to 35 days ]
  • Assessment of pharmacokinetic parameters in blood (t1/2) [ Time Frame: 28 to 35 days ]
  • Change from baseline in Body weight [ Time Frame: 28 to 35 days ]
  • Change from baseline in Fasting Blood Glucose [ Time Frame: 28 to 35 days ]
  • Change from baseline in Postprandial Blood Glucose [ Time Frame: 28 to 35 days ]
  • Change from baseline in postprandial Insulin profiles [ Time Frame: 28 to 35 days ]
  • Change from baseline in postprandial C-peptide profiles [ Time Frame: 28 to 35 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multiple Ascending Dose Study in Healthy Male Subjects and Overweight to Obese Male and Female Type 2 Diabetes Mellitus (T2DM) Patients
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of Repeated Subcutaneous Doses of SAR425899 in Healthy Male Subjects and Overweight to Obese Patients With Type 2 Diabetes Mellitus
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.
Detailed Description The total study duration is approximately 10-15 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: SAR425899

    Pharmaceutical form: solution for injection

    Route of administration: subcutaneous

  • Drug: placebo

    Pharmaceutical form: solution for injection

    Route of administration: subcutaneous

  • Drug: metformin

    Pharmaceutical form: tablet

    Route of administration: oral

Study Arms  ICMJE
  • Experimental: SAR425899 (healthy subjects)
    Once daily SC doses of SAR425899
    Intervention: Drug: SAR425899
  • Placebo Comparator: Placebo (healthy subjects)
    Once daily SC doses of placebo
    Intervention: Drug: placebo
  • Experimental: SAR425899 (T2DM Patients)
    Once daily SC doses of SAR425899 and two up titration steps in each dose cohort with metformin as background therapy
    Interventions:
    • Drug: SAR425899
    • Drug: metformin
  • Placebo Comparator: Placebo (T2DM Patients)
    Once daily SC doses of placebo and two up titration steps in each dose cohort with metformin as background therapy
    Interventions:
    • Drug: placebo
    • Drug: metformin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 14, 2018)
76
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2015)
40
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

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:
  • 95 mmHg <systolic blood pressure (SBP) <150 mmHg.
  • 45 mmHg <diastolic blood pressure (DBP) <100 mmHg.
  • 50 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.
  • Diagnosis of T2DM for at least 1 year with stable metformin prior to inclusion; comorbidities related to T2DM but otherwise healthy.
  • Normal vital signs supine:
  • 95 mmHg < SBP <160 mmHg
  • 45 mmHg < DBP <100 mmHg
  • 50 bpm < HR <100 bpm
  • Normal standard 12-lead ECG in supine position unless abnormality is clinically irrelevant.
  • Laboratory parameters in normal range unless abnormality is clinically irrelevant or strongly associated with T2DM; total bilirubin not to exceed ULN.
  • Fasting plasma glucose ≥90 mg/dL.
  • HbA1c ≥6.5% and ≤8.5%.
  • Females: Sterilization at least 3 months before inclusion or postmenopausal.

Both:

  • Signed written informed consent.
  • Not supervised/confined for legal or administrative reasons.
  • Male subject with partner of childbearing potential (including lactating women) must use double contraception method.
  • Male subject with pregnant partner must use a condom up to 2 months after last dosing.
  • Male subject agreed not to donate sperm up to 2 months after last dosing.
  • Not undergoing physical training program/planning changes in activity; not vegetarian or following special diet.

Exclusion criteria:

Healthy subjects:

  • History of clinically relevant disease/signs of acute illness.
  • History of drug hypersensitivity/allergic disease.
  • Smoking more than 5 cigarettes/day.
  • Any medication within 14 days before inclusion or within 5 times elimination/pharmacodynamic half-life of the medication and during study; vaccination within last 28 days, biologics given within 4 months before inclusion.

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.
  • Vaccination within last 28 days, any biologics within 4 months before inclusion.
  • 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.
  • Diabetic neuropathy, retinopathy, nephropathy or renal impairment.
  • Hepatic impairment.
  • Unstable hypo- or hyperthyroidism.

Both:

  • Headaches/migraine.
  • Recurrent nausea/vomiting.
  • Blood donation within 1 month before inclusion.
  • Symptomatic postural hypotension, irrespective of decrease in BP, or asymptomatic postural hypotension defined as decrease in SBP ≥20 mmHg within 3 minutes when changing from supine to standing.
  • History/presence of drug or alcohol abuse.
  • Positive result: hepatitis B surface antigen, anti-hepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2 antibodies.
  • Any condition affecting gastric emptying or absorption from GI tract.
  • Surgically treated obesity, bariatric surgery.
  • Severe dyslipidemia with fasting triglycerides >450 mg/dL.
  • History of pancreatitis or pancreatectomy.
  • Amylase/lipase >3 ULN.
  • History of thyroid cancer or a genetic condition that predisposes to thyroid cancer.
  • Elevated basal calcitonin.

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02411825
Other Study ID Numbers  ICMJE TDR13700
2014-004216-10 ( EudraCT Number )
U1111-1163-1209 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP