Clinical trial NCT04700436: Efficacy and Safety of EzetimiBe/Rosuvastatin in Diabetic Dislipidemia With Hypertriglyceridaemia
Official title: A Multi-center, Randomized, Open-label, Active-controlled, Phase IV Clinical Trial to Evaluate the Efficacy and Safety of EzetimiBe/Rosuvastatin Diabetic Dislipidemia With Hypertriglyceridaemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Endocrine System Diseases
Nutritional and Metabolic Diseases
Diabetes Mellitus, Type 2
Dyslipidemias
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Gangnam Severance Hospital
First posted: 2021-01-07
Enrollment: 240
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG \> 200 mg/dL).

Detailed description: The purpose of this study is to compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG \> 200 mg/dL).

Eligibility criteria: Inclusion Criteria:

Screening (Visit 1) Inclusion Criteria

1. Korean men and women aged 40 to 75
2. Patients who have been diagnosed with type 2 diabetes based on clinical judgment and satisfy diabetes diagnosis criteria
3. Those who have no history of statin administration or who are receiving low- and moderate-intensity statin, and who have the following laboratory values on an empty stomach

   * Low density lipoprotein-cholesterol (LDL-C) ≥ 100 mg/dL (direct measurement result)
   * 200 mg/dL ≤ Triglyceride (TG) ≤ 499 mg/dL
4. Those with less than 9% HbA1C
5. Those who voluntarily agreed to participate in this clinical trial and signed a written ICF

Randomization (Visit 2) Inclusion Criteria

1. Persons with compliance 80% or more during Suvast tablet 5 mg Run-in period and with good TLC by investigator's judgment
2. LDL-C ≥ 70 mg/dL (direct measurement result) at baseline (visit 2)
3. Triglyceride (TG) ≥ 150 mg/dL at baseline (visit 2)

Exclusion Criteria:

1. Patients with hypersensitivity to the main ingredient (Ezetimibe or Rosuvastatin) and ingredients of IP
2. Pregnant and lactating women, and women and men of childbearing potential who do not agree to conduct appropriate contraception during clinical trial
3. Patients with Body Mass Index (BMI) \< 15 kg/ m2 or \> 35 kg/m2
4. Persons with the following medical history or surgical/interventional history

   * Atherosclerotic disease occurring within 24 weeks at screening
   * Myopathy including rhabdomyolysis
   * Patients who have had a history of drug or alcohol abuse, or who have met drug or alcohol abuse criteria within 1 year at screening
   * Major mental illness (depression, bipolar disorder, etc.)
   * Malignant tumor within 5 years at screening
5. Persons with the following comorbidities and laboratory abnormalities

   * CK ≥ 2 X ULN
   * Patients with severe hepatopathy (AST or ALT \> 5 X ULN)
   * Patients with unexplained persistent ALT elevation opinion or active liver disease
   * TSH (Thyroid stimulating hormone) \> 1.5 X ULN or those who do not maintain stable thyroid stimulating hormone level by investigator's judgment
   * Uncontrolled hypertension (greater than sitBP 160/100 mmHg at screening)
   * Renal disorder patients with severe renal failure (creatinine clearance (CLcr)
6. Those who have the following history of drug administration within 3 months at screening

   * Non-statin lipid modulators
   * Foods or drugs that affect lipid control
   * Systemic steroids
7. Those who are expected to administer contraindication drugs during clinical trial, including screening
8. Those who have persistent history of drinking within 1 week at clinical trial participation or who are unable to perform TLC due to continuous drinking during clinical trial
9. Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorptioin
10. Those who received other IPs or investigational medical devices within 30 days at screening
11. Patients judged to be ineligible to participate in clinical trial by investigator's decision

Primary outcomes:
measure: LDL-C change rate (percent, %)
timeFrame: Baseline and 16 weeks
measure: Triglyceride (TG) change rate (percent, %)
timeFrame: Baseline and 16 weeks
Secondary outcomes:
measure: Change rates (percent, %) of LDL-C and Triglyceride (TG)
timeFrame: Baseline and 4 weeks
measure: Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C
timeFrame: Baseline, 4 weeks, and 16 weeks
measure: Percent (%) of subjects with a 50% or more reduction in LDL-C level
timeFrame: 4 weeks and 16 weeks
measure: Percent (%) of subjects with LDL-C below 70 mg/dL
timeFrame: 4 weeks and 16 weeks
measure: Changes of lipoproteins (ApoA1, ApoB)
timeFrame: Baseline and 16 weeks
measure: Changes of lipoproteins (ApoB/ApoA1 ratio)
timeFrame: Baseline and 16 weeks
measure: Change of HOMA-IR
timeFrame: Baseline and 16 weeks
measure: Change of HbA1C (percentage, %)
timeFrame: Baseline, 4 weeks, and 16 weeks
measure: Change (mg/dL) of Fasting Plasma Glucose (FPG)
timeFrame: Baseline, 4 weeks, and 16 weeks
measure: Change (mg/dL) of hs-CRP
timeFrame: Baseline and 16 weeks
measure: Changes of plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) levels at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC
timeFrame: Baseline and 16 weeks
measure: On the graphs at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC, total Area Under the Curve (tAUC) of each plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL)
timeFrame: Baseline and 16 weeks
measure: Adverse event
timeFrame: Baseline and 16 weeks
measure: Blood pressure
timeFrame: Baseline and 16 weeks
measure: Pulse
timeFrame: Baseline and 16 weeks
measure: Electrocardiogram (12-lead ECG)
timeFrame: -4 weeks and 16 weeks
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Bucheon
country: Korea, Republic of
facility: The Catholic University of Korea, Bucheon St. Mary's Hospital
city: Cheonan
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Cheonan
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Yeongnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Gangdong
country: Korea, Republic of
facility: Kyung Hee University Hosipital at Gangdong
city: Goyang-si
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Goyang-si
country: Korea, Republic of
facility: Myongji Hospital
city: Guri-si
country: Korea, Republic of
facility: Hanyang University Guri Hospital
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Hwaseong-si
country: Korea, Republic of
facility: Hallym University Medical Center-Dongtan
city: Inchon
country: Korea, Republic of
facility: Inha University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Sŏngnam
country: Korea, Republic of
facility: Gachon University, Donginchoen Gil Hospital
city: Sŏngnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
affiliation: Principal Investigator
name: Kyong Soo Park, Dr.
role: PRINCIPAL_INVESTIGATOR
References: