Safety and Efficacy Study of TRC150094 to Improve the CV Risk in Subjects With Diabetes, Dyslipidemia and Hypertension
- Registration Number
- NCT03254446
- Lead Sponsor
- Torrent Pharmaceuticals Limited
- Brief Summary
The phase III trial is designed with an aim of determining the efficacy of Investigational Product TRC150094 in concurrently reducing non-traditional risk factors for CV risk i.e., HbA1c, MAP and non-HDL cholesterol. This study will be a randomized, double blind, parallel group, placebo controlled, multi-centre, multinational study in 1250 subjects. All the study subjects will receive once daily dose of TRC150094 45 mg or placebo tablets in addition to their standard of care, for 24 weeks followed by roll over to a safety extension phase of 26 weeks.
- Detailed Description
TRC150094 is an Investigational Product for the treatment of CV risk associated with non-traditional risk factors ie, diabetes, hypertension and dyslipidemia, which acts by increasing the energy expenditure and restoring mitochondrial flexibility which is deranged in patients with these risk factors. Treatment with TRC150094 has shown clinically meaningful benefits in well-established contributors of CV risk i.e., insulin resistance and hyperglycemia, SBP as well as non-traditional risk factors i.e. non-HDL cholesterol and MAP, over and above standard of care.
The phase III trial is designed with an aim of determining the efficacy of TRC150094 in concurrently reducing non-traditional risk factors for CV risk i.e., HbA1c, MAP and non-HDL cholesterol. This study will be a randomized, double blind, parallel group, placebo controlled, multi-centre, multinational study in 1250 subjects. All the study subjects will receive once daily dose of TRC150094 45 mg or placebo tablets in addition to their standard of care, for 24 weeks followed by roll over to a safety extension phase of 26 weeks.
Primary Objective of the study is, To evaluate the efficacy of TRC150094 in improving cardiovascular (CV) risk in subjects with diabetes, dyslipidemia and hypertension Secondary Objectives of the study are,
1. To evaluate safety of TRC150094 in subjects with diabetes, dyslipidemia and hypertension
2. To evaluate extended safety profile of TRC150094 beyond 24 weeks of treatment in subjects with diabetes, dyslipidemia and hypertension
In this study there will be five visits at week 4, 12, 24, 36 and 50 after enrolment.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1250
- Male and female subjects in the age range 30-70 years (both inclusive)
- BMI in the range 23-39 (inclusive) kg/m2
- HbA1C ≥7.5 %
- 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.
- Non HDL-cholesterol ≥ 160 mg/dL.
- Mean Arterial Pressure (MAP) ≥100 mm Hg based on average of 24 hours' ambulatory blood pressure monitoring (ABPM) with or without antihypertensive 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.
- Willing to give written informed consent
- Ability to adhere to the study restrictions and assessments schedule
- Uncontrolled hypertension: SBP of ≥ 180 mm Hg and DBP ≥ 110 mmHg based on average of 24 hours' ambulatory blood pressure monitoring.
- HbA1C > 10 % at screening.
- Serum triglycerides >400 mg/dL.
- LDL-cholesterol >300 mg/dL or medical history/clinical evidence of familial hyperlipidemic disorder.
- Subjects on Insulin or Sodium Glucose Co-Transporter 2 (SGLT2) inhibitors.
- Acute coronary syndrome (ACS) or stroke or any revascularization within last 6 months.
- Subjects having untreated thyroid dysfunction (TSH <0.3 or >5.5 µIU/mL) or hormone related obesity disorder.
- Subjects with liver enzymes (SGOT, SGPT) more than 3X of upper limit of normal value.
- eGFR <30 mL/min as evaluated by Modification of Diet in Renal Disease (MDRD) method.
- Seropositive for HIV, Hepatitis B or Hepatitis C.
- History of alcohol or drug abuse, psychiatric disorder, any bleeding disorder, malignancy in last 3 years.
- Pregnant or lactating women.
- Female of childbearing potential, who are neither surgically sterilized nor willing to use reliable contraceptive methods (double barrier methods or intrauterine device).
- Male subjects with partners of childbearing potential not willing to use reliable contraception methods.
- 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.
- Intake of any investigational drug within 3 months prior to the first dose of study drug.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching Placebo Tablet to be administered orally once a day for 50 weeks TRC150094 45 mg TRC150094 TRC150094 45 mg Tablet to be administered orally once a day for 50 weeks
- Primary Outcome Measures
Name Time Method Change in mean arterial pressure (MAP), non-HDL cholesterol and HbA1c 24 Weeks 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
Change in Joint British Society recommendations on the prevention of cardiovascular disease 3rd iteration (JBS3) risk score 24 Weeks 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
- Secondary Outcome Measures
Name Time Method Change in non-HDL cholesterol 24 Weeks Mean change in non-HDL cholesterol from baseline to 24 weeks of treatment
Change in MAP 24 Weeks Mean change in MAP from baseline to 24 weeks of treatment
Change in HbA1c 24 Weeks Mean change in HbA1c from baseline to 24 weeks of treatment
Trial Locations
- Locations (21)
Ashirwad Hospital & Research Centre
🇮🇳Ulhasnagar, Maharashtra, India
De La Salle Heath Sciences Institute
🇵🇭Dasmariñas, Cavite, Philippines
Diabetes ,Thyroid and Endocrine Centre
🇮🇳Jaipur, Rajasthan, India
Davao Doctors Hospital
🇵🇭Davao City, Philippines
Angeles University Foundation Medical Center
🇵🇭Angeles City, Pampanga, Philippines
Indian Institute of Diabetes
🇮🇳Thiruvananthapuram, Kerala, India
Supe Heart and Diabetes Hospital and Research Centre,
🇮🇳Nashik, Maharashtra, India
Dayanand Medical College & Hospital
🇮🇳Ludhiana, Punjab, India
Apollo Hospitals, PR No. 3-5-836 to 838, Near Old MLA Quarters,
🇮🇳Hyderabad, Telangana, India
Government Medical College, Government Medical College Campus,
🇮🇳Calicut, Kerala, India
Rua Silva Jardim
🇧🇷São Bernardo Do Campo, SP, Brazil
Avenida Angélica
🇧🇷São Paulo, CEP, Brazil
Av. Farroupilha, 8001 Prédio 21, Recepção C, Bairro São José - Canoas/RS
🇧🇷Canoas, Brazil
Rua Coronel Aureliano de Camargo,905, Centro,
🇧🇷Tatuí, Brazil
Bangalore Diabetes Centre, No. 426, 4th Cross, 2nd block, kalyan nagar,
🇮🇳Bangalore, Karnataka, India
Lisie Hospital
🇮🇳Kochi, Kerala, India
Medipoint Hospitals Pvt. Ltd
🇮🇳Pune, Maharashtra, India
S.R Kalla Memorial Gastro and General Hospital
🇮🇳Jaipur, Rajasthan, India
St. Paul's Hospital
🇵🇭General Luna, Saint Iloilo City, Philippines
BAPS Pramukh Swami Hospital,
🇮🇳Sūrat, Gujarat, India
Comitê de ética em Pesquisa do Hospital Pró Cardíaco
🇧🇷Rio De Janeiro, Botafogo, Brazil