Clinical trial NCT04141241: Phase 2a Study to Evaluate the Safety and Efficacy of PH100 Tablet in T2DM Patients With Recent Cardiovascular
Official title: Multi-center, Randomized, Double-blinded, Placebo-controlled, Parallel-design, 12-week, Therapeutic Exploratory, Phase 2a Study to Evaluate the Safety and Efficacy of PH100 Tablet in T2DM Patients With Recent Cardiovascular Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus With Circulatory Complciation
Keywords: T2DM with Recent Cardiovascular Complications
Lead sponsor: Bota Bio Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-10-28
Enrollment: 82
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This is a Multi-center, Randomized, Double-blinded, Placebo-controlled, Parallel-design, 12-Week, Therapeutic exploratory, Phase IIa Study which will patients with type 2 diabetes mellitus and recent cardiovascular complications.

Detailed description: After a screening, 114 patients will be stratified randomized in a 1:1:1 ratio to the 3 arms (PH100 800mg/day, PH100 1600mg/day, Placebo) to evaluate the safety and efficacy of PH100.

Subjects will visit the centers on Week 4, 8 and 12 during the entire 12-week treatment period.

Eligibility criteria: Inclusion Criteria:

1. Age \>= 19 years old
2. Subjects who have been treated for cardiovascular complications (stent insertion due to angina pectoris, myocardial infarction, cerebral ischemia, peripheral vascular disease) within 4 weeks prior to baseline
3. T2DM patients who diagnosed with type 2 diabetes prior to or above cardiovascular complications and have been taking oral hypoglycemic agents and/or receiving insulin treatment before the above complication occurred
4. Subjects taking a stable dose of statins and are anticipated to have no change in dose during the duration of the study
5. The following is confirmed through screening:

   * AST/ALT ≤ 2.5 X ULN
   * Creatinine ≤ 1.5 X ULN
   * Hemoglobin ≥ 10 g/dL
   * 6.5% ≤ HbA1c ≤ 11%
6. Women of child-bearing potential who have negative pregnancy testing results and have agreed to use appropriate measures of contraception\* during the duration of the study (\*appropriate contraception is defined as women of child-bearing potential, excluding women in whom more than 52 weeks have passed since their last period, using the following methods: surgical sterilization, intrauterine device, condoms, barrier contraceptives, absolute abstinence)
7. Subjects who have signed the informed consent form (or whose legal representative has signed) and who are deemed to be able to follow the requirements of the study

Exclusion Criteria:

1. T2DM patients, secondary DM patients, Gestational DM patients
2. Subjects who have a history of secondary hypertension or have a disease history of suspicious secondary hypertension. This includes but is not restricted to: aortic coarctation, primary hyperaldosteronism, renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.
3. Subjects taking anti-inflammatory agents including corticosteroids/NSAIDs (However, maximum 100mg of aspirin per day is allowed)
4. Subjects with chronic liver/renal disease or malignancy
5. Supplements containing kajime or kajime derivatives (e.g. Seapolynol, Fibroboost, Fibronol, Seanol Longevity Plus, Circulate, Alginol, PC Eckonia Cava, Seanol, Seanol-F, Seanol-EX, Seanol-TX, Venusen, Memories with Seanol-P, Astaxanthol, Brilliant Vision with Seanol-P, Gly-Control, Gyne-Andro-Plex, Lipid Balance, Seanol with Broccoraphanin, Marine D3, Botabio everyone, Botabio power, Botabio red, Botabio premium, Botabio Eplus) and related medications, or subjects who have a history of hypersensitivity to high iodine containing products (seaweed, shellfish, etc.)
6. Pregnant, breast-feeding subjects or subjects who have plans for pregnancy
7. Subjects who have taken supplements containing kajime or kajime derivatives within 4 weeks of baseline (e.g., Seapolynol, Fibroboost, Fibronol, Seanol Longevity Plus, Circulate, Alginol, PC Eckonia Cava, Seanol, Seanol-F, Seanol- EX, Seanol-TX, Venusen, Memories with Seanol-P, Astaxanthol, Brilliant Vision with Seanol-P, Gly-Control, Gyne-Andro-Plex, Lipid Balance, Seanol with Broccoraphanin, Marine D3, Botabio everyone, Botabio power, Botabio red, Botabio premium, Botabio Eplus)
8. Subjects who have participated in another clinical trial within 4 weeks of baseline and have taken other clinical trial medications
9. Subjects who have received treatment for or who test positive for HBsAg, HCV antibody, or HIV at baseline
10. Subjects who have an acute inflammatory disease other than cardiovascular complications within 4 weeks of baseline
11. Subjects who have gastrointestinal diseases that may affect the absorption, distribution, metabolism, and excretion of drugs (e.g. Crohn's disease) and subjects who have a history of gastrointestinal surgery (with the exception of appendectomy and hernia repair), or subjects with active gastritis, gastrointestinal/rectal bleeding, active inflammatory bowel disease within the past 12 months
12. Subjects with autoimmune disease (e.g. rheumatoid arthritis) or who require chronic anti-inflammatory treatment
13. Subjects with a history of drug or alcohol abuse
14. Subjects who are judged not to be appropriate for participation in the study or who have a medical condition that may have an influence on the study results

Primary outcomes:
measure: hs-CRP (high-sensitivity C-reactive protein)
timeFrame: Visit 2(Baseline Visit) vs Visit 5(week 12)
Secondary outcomes:
measure: hs-CRP
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8)
measure: hs-CRP: monthly rate of change
timeFrame: Between Visit 2(Baseline Visit) and Visit 3(week 4), Between Visit 3(week 4) and Visit 4(week 8), Between Visit 4(week 8) and Visit 5(week 12)
measure: Interleukin-6 (IL-6)
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Tumor Necrosis Factor-α (TNF- α)
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Malondialdehyde (MDA)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Oxidized Low Density Lipoprotein (Oxidized LDL)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Glutathione Peroxidase (GPX)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Superoxide Dismutase (SOD)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Total AntiOxidants (TAS)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: HbA1c
timeFrame: Visit1(screening), Visit 5(week 12)
measure: Adiponectin
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Free Fatty Acid
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: High Density Lipoprotein-cholesterol (HDL-C)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Low Density Lipoprotein-cholesterol (LDL-C)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Triglyceride (TG)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Total Cholesterol (TC)
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Homocysteine
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Fibrinogen
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: MACE (Major Adverse Cardiovascular Events)
timeFrame: Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Left Ventricular Ejection Fraction
timeFrame: Visit 2(Baseline Visit), Visit 5(week 12)
measure: Blood Pressure (Systolic Blood Pressure, Diastolic Blood Pressure)
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: BMI
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Waist-hip ratio
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: AE (Adverse Events)
timeFrame: Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Pulse
timeFrame: Visit 1(Screening), Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
measure: Body Temperature
timeFrame: Visit 1(Screening), Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Other outcomes:
Locations:
Study officials:
References: