Type 2 Diabetes MellitusPhase 1NCT02411825
Multiple Ascending Dose Study in Healthy Male Subjects and Overweight to Obese Male and Female Type 2 Diabetes Mellitus (T2DM) Patients
A Phase 1 study testing SAR425899 and metformin in people with Type 2 Diabetes Mellitus, run by Sanofi at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- SAR425899 and metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2015to Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Primary Objective:
To assess in healthy adult male subjects:
Read more
- 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.
Read the detailed description
The total study duration is approximately 10-15 weeks.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- SAR425899, placebo, metformin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR425899Drug
Pharmaceutical form: solution for injection
Route of administration: subcutaneous
placeboDrug
Pharmaceutical form: solution for injection
Route of administration: subcutaneous
metforminDrug
Pharmaceutical form: tablet
Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| SAR425899 (healthy subjects) | Experimental | Once daily SC doses of SAR425899 Receives: Drug: SAR425899 |
| Placebo (healthy subjects) | Placebo comparator | Once daily SC doses of placebo Receives: 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 Receives: 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 Receives: Drug: placebo; Drug: metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Measured: 28 to 35 days
Secondary outcomes (20)
Changes in vital signs
Measured: 28 to 35 days
Changes in physical examination
Measured: 28 to 35 days
Changes in ECG
Measured: 28 to 35 days
Changes in clinical laboratory parameters (hematology)
Measured: 28 to 35 days
Changes in clinical laboratory parameters (biochemistry)
Measured: 28 to 35 days
Changes in body temperature
Measured: 28 to 35 days
Change from baseline in biomarkers (FGF21)
Measured: 28 to 35 days
Change from baseline in biomarkers (lipid biomarker)
Measured: 28 to 35 days
Change from baseline in biomarkers (incretins)
Measured: 28 to 35 days
Assessment of pharmacokinetic parameters in blood (AUC)
Measured: 28 to 35 days
Assessment of pharmacokinetic parameters in blood (Cmax)
Measured: 28 to 35 days
Assessment of pharmacokinetic parameters in blood (t1/2)
Measured: 28 to 35 days
Assessment of pharmacokinetic parameters in urine (Ae0-24)
Measured: 28 to 35 days
Assessment of pharmacokinetic parameters in urine (fe0-24)
Measured: 28 to 35 days
Change from baseline in Body weight
Measured: 28 to 35 days
Change from baseline in Fasting Blood Glucose
Measured: 28 to 35 days
Change from baseline in Postprandial Blood Glucose
Measured: 28 to 35 days
Change from baseline in postprandial Insulin
Measured: 28 to 35 days
Change from baseline in postprandial C-peptide profiles
Measured: 28 to 35 days
Change from baseline in HbA1c
Measured: 28 to 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study startMar 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02411825
- Sponsor's protocol ID
- TDR13700
- Other IDs
- 2014-004216-10, U1111-1163-1209, 2014
- Status last verified
- Jun 2018
- First submitted
- 24 Mar 2015
- Last updated
- 15 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 31808298Tillner 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.
PubMed 30091218
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02411825
- Acronym / sponsor ID
- TDR13700
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Mar 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SAR425899 (healthy subjects) | Experimental | Drug: SAR425899Once daily SC doses of SAR425899 |
| Placebo (healthy subjects) | Placebo comparator | Drug: placeboOnce daily SC doses of placebo |
| SAR425899 (T2DM Patients) | Experimental | Drug: SAR425899, Drug: metforminOnce daily SC doses of SAR425899 and two up titration steps in each dose cohort with metformin as background therapy |
| Placebo (T2DM Patients) | Placebo comparator | Drug: placebo, Drug: metforminOnce daily SC doses of placebo and two up titration steps in each dose cohort with metformin as background therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- 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.
Key exclusion criteria (35 listed)
- 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.
- History/presence of clinically relevant disease/signs of acute illness not related to patient's metabolic status.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAR425899Pharmaceutical form: solution for injection Route of administration: subcutaneous | Drug | SAR425899 (T2DM Patients), SAR425899 (healthy subjects) |
| placeboPharmaceutical form: solution for injection Route of administration: subcutaneous | Drug | Placebo (T2DM Patients), Placebo (healthy subjects) |
| metforminPharmaceutical form: tablet Route of administration: oral | Drug | Placebo (T2DM Patients), SAR425899 (T2DM Patients) |
Primary outcome
Number of adverse events
Time frame: 28 to 35 days
20 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2018.
- Derived from this study: PubMed 31808298Visentin 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.
- Derived from this study: PubMed 30091218Tillner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SAR425899 and metformin in people with Type 2 Diabetes Mellitus, run by Sanofi at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events (time frame: 28 to 35 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02411825, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2018.