Clinical trial NCT03317028: CS02 vs Placebo With Metformin in Type 2 Diabetes Mellitus (T2DM)
Official title: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of CS02 Tablet in Combination With Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: T2DM With Inadequate Glycemic Control
Lead sponsor: Center Laboratories, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-23
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to compare the efficacy and safety of 3 doses CS02 Tablet in combination with a stable dose of metformin monotherapy against CS02 PTM (placebo) Tablet in combination with a stable dose of metformin monotherapy over a 12 weeks treatment period in subjects with type 2 diabetes mellitus with inadequate glycemic control on metformin alone.


Eligibility criteria: Inclusion Criteria:

1. Subjects with diagnosis of type 2 diabetes mellitus at least 12 weeks prior to Visit 1;
2. Outpatient, either male or female, aged 20 years or older from Taiwan and aged 18 years or older from united States; all subjects are ≤75 years old;
3. Subjects with a stable diet and exercise program for ≧8 weeks prior to Visit 1;
4. Subjects with HbA1c value ≧7.0% and ≦10.0% at Visit 1;
5. Subjects with a stable dose of metformin monotherapy of ≥1500 mg/day at least 12 weeks before randomization (Visit 2);
6. Body mass index (BMI) between 20.0 and 45.0 kg/m2at Visit 1;
7. Subjects have adequate liver function, defined as serum total bilirubin≤1.5 times the upper limit of normal (uLN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤3 times uLN at Visit 1;
8. Subjects have estimated glomerular filtration rate (e-GFR)\* values of≧ 45ml/min/1.73m2 at Visit1;
9. Female subjects of childbearing potential， defined as women≤ 55 years old or history of amenorrhea ≤ 12 months prior to the study entry or not surgically sterile, must have a negative pregnancy test at Visit 1 and agree to use a highly effective contraceptive method during the study period;
10. Willing to provide a written informed consent form;
11. Willingness and ability to comply with treatment plans, scheduled visits, required laboratory tests, and other study procedures;

Exclusion Criteria:

1. Subjects with type 1 diabetes mellitus, secondary diabetes mellitus, or gestational diabetes;
2. Subjects with acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma at Visit 1 or Visit 2;
3. Subjects with hypotension (average systolic pressure \< 90 mm Hg\*) at Visit 1 or Visit 2;
4. Subjects with cardiogenic shock within 8 weeks prior to Visit 1;
5. Subjects with sick sinus syndrome, second- or third-degree atrioventricular block (AV block);
6. Subjects with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes);
7. Subjects with recurrence or history of transient ischemic attack or coronary artery bypass surgery;
8. Subjects with history of cerebrovascular attack, myocardial infarction, serious cardiac disease (New York Heart Association NYHA Class III to IV), left ventricular ejection fraction≦40% within 12 weeks prior to Visit 1, or those with cardiovascular disease or cerebrovascular disease that may affect the administration of IP tablets (CS02) or its safety assessment in the opinion of the investigator or sub-investigator;
9. Female subjects who are nursing or pregnant during the study period;
10. Subjects are on a weight loss program and not in the maintenance phase or have started a weight loss medication including but not limited to Orlistat, Phentermine, Osymia, or Belviq or have undergone bariatric surgery within 8 weeks prior to Visit 1 or any type of surgery planned during the study;
11. Subjects with a clinically severe gastrointestinal disorder including diabetic gastroparesis; irritable bowel disease; recurrent episodes of nausea, vomiting, diarrhea and abdominal pain within 12 weeks prior to Visit 1;
12. Subjects have a history or current of substance or alcohol abuse;
13. Subjects have uncontrolled psychiatric disorder(s);
14. Subjects are less than 5 years free of malignancy (except for cured basal cell carcinoma of skin and cured carcinoma in situ of the uterine cervix);
15. Subjects have participated in another clinical trial within the last 12 weeks prior to Visit 1;
16. Subjects who are considered unreliable as to medication compliance or adherence to scheduled appointments, or inappropriate for inclusion per investigators, judgments;

Primary outcomes:
measure: The HbA1c treatment effect among CS02 groups and the Placebo group
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas, Inc.
state: Arkansas
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Hialeah
country: United States
facility: The Community Research of South Florida
state: Florida
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans general Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital_Linkou
Study officials:
References:
citation: Wang CY, Huang KC, Lu CW, Chu CH, Huang CN, Chen HS, Lee IT, Chen JF, Chen CC, Chen CS, Hsieh CH, Tien KJ, Chien HY, Huang YY, Hsu JP, Shane GT, Chang AC, Wu YC, Sheu WH. A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes. J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4063-e4071. doi: 10.1210/clinem/dgac436.