To evaluate the efficacy and safety of TRC150094 as an Add On to Standard of Care in Improving Cardiovascular Risk in Subjects with Diabetes, Dyslipidemia and Hypertension
Scientific Title of Study
A Phase III Randomized, Double Blind, Parallel Group, Placebo Controlled, Multi-centre, Multinational Study to Evaluate Efficacy and Safety of TRC150094 as an Add On to Standard of Care in Improving Cardiovascular Risk in Subjects with Diabetes, Dyslipidemia and Hypertension
1. Male and female subjects in the age range 30-70 years (both inclusive)
2. BMI in the range 23-39 (inclusive) kg/m2
3. HbA1C ≥7.5 %
4. Stable therapy of ≤2 oral hypoglycemic agents for at least two months prior to screening at doses that are appropriate for the duration of the study in the judgment of the investigator.
5. Non HDL-cholesterol ≥ 160 mg/dL.
6. Mean Arterial Pressure (MAP) ≥100 mm Hg based on average of 24 hours’ambulatory blood pressure monitoring with or without anti-hypertensive treatment (subjects will have to be on stable dose of anti-hypertensive treatment for at least two months prior to screening); Dose should be appropriate for the
duration of the study in the judgment of the investigator.
7. Willing to give written informed consent
8. Ability to adhere to the study restrictions and assessments schedule
ExclusionCriteria
Details
1. Uncontrolled hypertension: SBP of ≥ 180 mm Hg and DBP ≥ 110 mmHg based on average of 24 hours’ ambulatory blood pressure monitoring.
2. HbA1C > 10 % at screening.
3. Serum triglycerides >400 mg/dL.
4. LDL-cholesterol >300 mg/dL or medical history/clinical evidence of familial hyperlipidemic disorder.
5. Subjects on Insulin or Sodium Glucose Co-Transporter 2 (SGLT2) inhibitors.
6. Acute coronary syndrome (ACS) or stroke or any revascularization within last 6 months.
7. Subjects having untreated thyroid dysfunction (TSH <0.3 or >5.5 μIU/mL) or hormone related obesity disorder.
8. Subjects with liver enzymes (SGOT, SGPT) more than 3X of upper limit of normal value.
9. eGFR <30 mL/min as evaluated by MDRD method
10. Seropositive for HIV, Hepatitis B or Hepatitis C.
11. History of alcohol or drug abuse, psychiatric disorder, any bleeding disorder, malignancy in last 3 years.
12. Pregnant or lactating women.
13. Female of childbearing potential, who are neither surgically sterilized nor willing to use reliable contraceptive methods (double barrier methods or intrauterine device).
14. Male subjects with partners of childbearing potential not willing to use reliable contraception methods.
15. Clinically significant abnormal physical findings, laboratory results, ECG findings and/or any other clinical observation or history during the screening examination, which would interfere with the objectives of the study.
16. Intake of any investigational drug within 3 months prior to the first dose of study drug.
17. In the opinion of the investigator, subject is unable to cooperate with any study procedures, unlikely to adhere to the study procedures, keep appointments, or plan to relocate during the study.
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Mean change in weighted average composite score of change in mean arterial pressure (MAP), non-HDL cholesterol and HbA1c from baseline to 24 weeks of treatment between arms
Mean change in Joint British Society recommendations on the prevention of cardiovascular disease 3rd iteration (JBS3) risk score at the end of 24 weeks of treatment between arms
Week 24
Secondary Outcome
Outcome
TimePoints
Mean change in MAP from baseline to 24 weeks of treatment
Mean change in non-HDL cholesterol from baseline to 24 weeks of treatment
Mean change in HbA1c from baseline to 24 weeks of treatment
Total Sample Size="1035" Sample Size from India="880" Final Enrollment numbers achieved (Total)= "1039" Final Enrollment numbers achieved (India)="986"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study will be a randomized, double blind, parallel group, placebo controlled, multi-centre, multinational study. All the study subjects will receive once daily dose of TRC150094 45 mg or placebo tablets. This dose level is based on the assessment of safety, efficacy and PK data obtained from Phase I and II studies.The study includes screening, randomization, 24 weeks in main study, 26 weeks in safety extension period and post treatment follow up visit, 4 weeks post completion of treatment period.Subjects completing 24 weeks of main study will be rolled over to safety extension phase of 26 weeks where they will continue to receive either test product, TRC150094 45 mg, or matching placebo according to their initial randomization in the study.
Subjects completing visit 7 (50 weeks ± 14 days of total treatment period) will not be further dispensed with study treatment as the subject has completed the safety extension period in the study. However, subject will need to visit study site for follow-up visit, 4 weeks post completion of study treatment.
In case, the last enrolled subject in the main study has completed 12 weeks’ study treatment (Visit 4, ± 7 days of treatment period), the subjects who are continuing in the safety extension phase will be informed to visit site as soon as possible on the next immediate available date. The subjects who are in the main study, will not be rolled over to the safety extension phase but shall complete total 24 weeks of treatment period.
Subjects continuing in safety extension phase post last enrolled subject completes 12 weeks of study treatment in the main study, should continue taking study medication and shall be asked to visit the site on the next immediate available date. The remaining study drug needs to be returned to site and accountability will be performed.
The subject will be discontinued from study treatment, in case the subject visits the site before 14 days of the next scheduled visit, no additional safety assessments will be done and safety evaluation of previous visit will be considered for analysis.
In case the subject visits the site within window period of upcoming scheduled visit, safety assessment for those subject will be performed as specified in the protocol for the scheduled visit.
All enrolled subjects will have to visit study site for follow up visit, 4 weeks post completion of treatment.