Phase 2a Study to Evaluate the Safety and Efficacy of PH100 Tablet in T2DM Patients With Recent Cardiovascular (PH100_IIa)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus With Circulatory Complciation
• Intervention / Treatment: Drug: Ecklonia cava Phlorotannin

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose PH100: 800mg/day; PH100 (Ecklonia cava Phlorotannin) 200mg/tablet; PH100 2 tablets (400mg) and Placebo 2 tablets BID during 12wks	Drug: Ecklonia cava Phlorotannin; Drugs that have been administered prior to participation in this study that are not expected to affect the results of this study will be accepted at the investigator's discretion.; Other Names: PH100
Experimental: High Dose PH100: 1600mg/day; - PH100 4 tablets (800mg) BID during 12wks	Drug: Ecklonia cava Phlorotannin; Drugs that have been administered prior to participation in this study that are not expected to affect the results of this study will be accepted at the investigator's discretion.; Other Names: PH100
Placebo Comparator: Placebo; Placebo 200mg/tablet; Placebo 4 tablets BID during 12wks	Drug: Ecklonia cava Phlorotannin; Drugs that have been administered prior to participation in this study that are not expected to affect the results of this study will be accepted at the investigator's discretion.; Other Names: PH100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hs-CRP (high-sensitivity C-reactive protein)	Change in hs-CRP level compared to baseline after 12 weeks of investigational product administration	Visit 2(Baseline Visit) vs Visit 5(week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hs-CRP	Change in hs-CRP level compared to baseline after 4 weeks, 8 weeks of investigational product administration	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8)
hs-CRP: monthly rate of change	Change in hs-CRP level monthly	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)
Interleukin-6 (IL-6)	Change in IL-6 [Inflammatory Marker]	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Tumor Necrosis Factor-α (TNF- α)	Change in TNF- α [Inflammatory Marker]	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Malondialdehyde (MDA)	Change in MDA [Biomarkers of oxidative stress]	Visit 2(Baseline Visit), Visit 5(week 12)
Oxidized Low Density Lipoprotein (Oxidized LDL)	Change in Oxidized LDL [Biomarkers of oxidative stress]	Visit 2(Baseline Visit), Visit 5(week 12)
Glutathione Peroxidase (GPX)	Change in GPX [Biomarkers of oxidative stress]	Visit 2(Baseline Visit), Visit 5(week 12)
Superoxide Dismutase (SOD)	Change in SOD [Biomarkers of oxidative stress]	Visit 2(Baseline Visit), Visit 5(week 12)
Total AntiOxidants (TAS)	Change in TAS [Biomarkers of oxidative stress]	Visit 2(Baseline Visit), Visit 5(week 12)
HbA1c	Change in HbA1c level compared to Visit1(screening) after 12 weeks of investigational product administration	Visit1(screening), Visit 5(week 12)
Adiponectin	Change in Adiponectin level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration	Visit 2(Baseline Visit), Visit 5(week 12)
Free Fatty Acid	Change in Free Fatty Acid level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration	Visit 2(Baseline Visit), Visit 5(week 12)
High Density Lipoprotein-cholesterol (HDL-C)	Change in HDL-C level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration [Lipid Profile]	Visit 2(Baseline Visit), Visit 5(week 12)
Low Density Lipoprotein-cholesterol (LDL-C)	Change in LDL-C level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration [Lipid Profile]	Visit 2(Baseline Visit), Visit 5(week 12)
Triglyceride (TG)	Change in TG level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration [Lipid Profile]	Visit 2(Baseline Visit), Visit 5(week 12)
Total Cholesterol (TC)	Change in TC level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration [Lipid Profile]	Visit 2(Baseline Visit), Visit 5(week 12)
Homocysteine	Change in Homocysteine level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration	Visit 2(Baseline Visit), Visit 5(week 12)
Fibrinogen	Change in Fibrinogen level compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration	Visit 2(Baseline Visit), Visit 5(week 12)
MACE (Major Adverse Cardiovascular Events)	Incidence rate of MACE (Major Adverse Cardiovascular Events) during investigational product administration	Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Left Ventricular Ejection Fraction	Change in LVEFF compared to Visit 2(Baseline Visit) after 12 weeks of investigational product administration by Echocardiogram	Visit 2(Baseline Visit), Visit 5(week 12)
Blood Pressure (Systolic Blood Pressure, Diastolic Blood Pressure)	Change in SiSBP, SiDBP	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
BMI	Change in BMI	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Waist-hip ratio	Change in Waist-hip ratio	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
AE (Adverse Events)	[Safety and Tolerability] Incidence of AEs during investigational product administration	Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Pulse	[Safety and Tolerability] Check the Vital Sign (pulse) every visit schedule	Visit 1(Screening), Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)
Body Temperature	[Safety and Tolerability] Check the Vital Sign (body temperature) every visit schedule	Visit 1(Screening), Visit 2(Baseline Visit), Visit 3(week 4), Visit 4(week 8), Visit 5(week 12)

Collaborators and Investigators

• Sponsor: Bota Bio Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2016
• Primary Completion (Actual): May 4, 2018
• Study Completion (Actual): May 4, 2018

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: T2DM with Recent Cardiovascular Complications
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: BOTAB-DBCVC-PH100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No