Type 2 Diabetes
Conditions
Interventions
Product Code: PG232
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: CPL207280-51
Current Sponsor code: CZ25
Other descriptive name: CPL207280-51
Concentration unit: mg milligram(s)
Sponsors
Celon Pharma SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Gender: Male or female. 2. Age:18 to 75. 3. Subject with diagnosed type 2 diabetes, managed with diet and exercise alone, or who failed to achieve adequate glycemic control on a stable dose of metformin (or other antidiabetic drug except insulin and sulphonylureas) prior to Visit 1.1 and willing to discontinue it at least 10 days prior to randomization (on Visit 1.2) and during the study. 4. Subject has fasting plasma glucose level less than or equal 180 mg/dL on Visit 1.1 and Visit 1.2 5. Subject has calculated HOMA-IR value less than or equal to 7 (seven) at screening Visit 1.1. 6. Subject has body-mass index (BMI): = 18.50 kg/m² and = 40.00 kg/m² (with less than a 10% variation between Visit 1.1 and 1.2). 7. Subject, should have a HbA1c concentration less than or equal to 8.0%. 8. Subject has not received treatment with weight-loss drugs within the 3 months prior to Visit 1.1. 9. Subject has a systolic blood pressure less than or equal to 160 mm Hg and a diastolic blood pressure of less than or equal to 100 mm Hg at Screening on Visit 1.1 and 1.2. 10. Subject has the clinical laboratory evaluations [including fasting clinical chemistry, hematology and complete urinalysis (excluding glucose results)] on Screening Visit 1.1 and 1.2 within the reference range for the testing laboratory, unless the investigator deems the out-of-range results to be not clinically significant. 11. Subject has negative test results for hepatitis B surface antigen and antibody to hepatitis C virus, negative RT-PCR test results for COVID-19, negative antibody to HIV virus and no known history of human immunodeficiency virus. 12. Subject is considered by the investigator to be in a good health (other than being diabetic) as determined during the medical history review, physical examination findings, electrocardiogram and vital sign results, and clinical laboratory evaluations. 13. Subject has Estimated Glomerular Filtration Rate (eGFR) greater than 60 mL/min/1.73m^2 on Visit 1.1. and 1.2. 14. A female is eligible to participate if she is not pregnant (negative serum pregnancy test at Visit 1.1), not breastfeeding, and at least 1 of the following conditions applies: • Not a woman of childbearing potential (a woman is considered to be of non childbearing potential if she is post-menopausal for at least 12 months or is surgically sterile [hysterectomy, bilateral oophorectomy, tubal ligation]). • Woman of childbearing potential, who agree to use contraceptive methods during the Treatment Period and for at least 28 days after the last dose of the study drug. • The following are acceptable contraceptive methods: bilateral tubal occlusion, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, male or female condom with spermicide; and cap, diaphragm, or sponge with spermicide. 15. Male subjects must agree to use a barrier method of contraceptive (condom + spermicide gel) during the study and for at least 90 days after the last dose of the study drug. 16. Subject has the ability and willingness to comply with the requirements and restrictions of the study protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Subject has a c-peptide value less than 0.5 nmol/l on Visit 1.1 or 1.2. 2. Subject has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy), thoracic, or non-peripheral vascular surgery within 6 months prior to Visit 1.1. 3. Subject has a history of cardiac arrhythmia, systolic dysfunction, congestive heart failure, angina, myocardial ischemia or infarction, or stroke within 1 year prior to screening Visit 1.1, or the presence of an abnormal ECG on Visit 1.1 or 1.2 that, in the investigator's opinion, is clinically significant. 4. Subject has a history of drug abuse or a history of alcohol abuse within 2 years prior to Visit 1.1. 5. Patent has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. This criterion does not apply to basal cell or stage I squamous cell carcinoma of the skin. 6. Subject has an alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase level above normal range for the testing laboratory, active liver disease, on Visit 1.1 or 1.2. 7. Subject has a total bilirubin greater or equal 2 mg/dL on Visit 1.1 or 1.2 8. Subject is/ was lifetime (except gestational diabetes period) on any insulin treatment or is/was on any sulphonylureas treatment within 3 months prior to Visit 1.1 or received other anti-diabetic treatment 10 days prior to Visit 1.2. 9. Subject has a history of proteinuria =300 mg/day on a 12- or 24-hour urine collection within last year or an albumin/creatinine ratio greater or equal 300 µg/mg on Visit 1.1 or 1.2. If elevated, the subject may be rescreened within 1 week, and may be included in study with agreement between Principal Investigator, the Celon Pharma SA and Medical Monitor. 10. Subject has a history of any clinically significant retinopathy, which is defined as more than moderate nonproliferative diabetic retinopathy, any stage of proliferative diabetic retinopathy or any history of laser-treated retinopathy. 11. Subject has clinically significant peripheral or autonomic neuropathy. 12. Subject has a lifetime history of ulcerative colitis or Crohn's disease, or has undergone gastric resection. 13. Subject has a history of a psychiatric disorder that, in Principal Investigator opinion, will affect the subject ability to participate in the study. 14. Subject has a lifetime history of angioedema. 15. Subject has an acute, clinically significant illness within 30 days prior to Visit 1.1 or any other condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study. 16. Subject is not able to comply with the study scheduled visits. 17. Subject is participating in another investigational study or has taken any investigational drug within 90 days prior to screening Visit 1.1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy in lowering the plasma glucose during the OGTT after 2 weeks of CPL207280 treatment;Secondary Objective: •To determine the change in fasting plasma glucose, insulin, proinsulin, c-peptide, glucagon level after 2 weeks of CPL207280 treatment. •To determine the efficacy in plasma glucose Cmax and 2 h plasma level lowering during OGTT after 2 weeks of CPL207280 treatment, •To determine the efficacy in increasing plasma insulin level during OGTT after 2 weeks of CPL207280 treatment, •To assess the safety and tolerability of CPL207280 administered for 14 days, •To assess the pharmacokinetic (PK) profile of CPL207280 administered for 14 days. ;Primary end point(s): •Change From Day -1 to Day 14 in plasma glucose, evaluated through area under the plasma glucose concentration-time curve (AUC0–3 h) during the OGTT.;Timepoint(s) of evaluation of this end point: At the end of the treatment phase on day 14. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change From Day -1 to Day 14 in plasma glucose maximal concentration (Cmax) level during the OGTT • Change From Day -1 to Day 14 in plasma glucose concentration at 2 h timepoint level during the OGTT • Change From Day 1 to Day 15 in Fasting Plasma Glucose (FPG) • Change From Day 1 to Day 15 in Fasting Plasma Insulin (FPI) • Change From Day 1 to Day 15 in Fasting Plasma Proinsulin • Change From Day 1 to Day 15 in Fasting Plasma c-peptide • Change From Day 1 to Day 15 in Fasting Plasma glucagon • Change From Day -1 to Day 14 in plasma insulin, evaluated through area under the plasma insulin concentration-time curve (AUC0–3 h) during the OGTT. • Change From Day -1 to Day 14 in plasma insulin maximal concentration (Cmax) level during the OGTT • Change From Day -1 to Day 14 in plasma insulin concentration at 2 h timepoint plasma level during the OGTT • Potential effect on HbA1C value after 14 days of CPL207280 treatment • Absolute change from Day -2 to Day 14 in homeostasis model assessment of ß-cell function (HOMA-ß) • Number of Patients Who Experienced at Least Once Adverse Event related to the study product • Number of Patients Who Experienced at Least Once Hyperglycemia Episode. • Number of Patients Who Discontinued Study Due to an AE related to the study product • Hematologic, clinical chemistry, and urinalysis results. • Electrocardiogram (ECG) results. • Change From pre-dose value to mean of post-dose values of Total Bile Acids (TBA) on Day 1 and 14 • CPL207280 maximum observed concentration (Cmax) • CPL207280 time corresponding to occurrence of Cmax (tmax) • CPL207280 AUC from time zero to infinity (AUC0-8) • CPL207280 apparent terminal elimination half-life (t1/2) • CPL207280 apparent clearance (CL/F) • CPL207280 apparent volume of distribution during terminal phase (Vz/F) • CPL207280 concentration immediately prior to dosing (Ctrough). ;Timepoint(s) of evaluation of this end point: During the double-blind treatm | — |
Countries
Poland
Contacts
Public ContactClinical Development Leader
Celon Pharma SA
Outcome results
None listed