TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial
Deepa Joshi,1 Prashant GJ,1 Shohini Ghosh,1 Anookh Mohanan,1 Shashank Joshi,2 Viswanathan Mohan,3 Subhankar Chowdhury,4 Chaitanya Dutt,1 Nikhil Tandon5 1Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India; 2Lilavati Hospital, Mumbai, India; 3Dr. Mohan’s Diabetes Specialities Centre (Madras Diabe...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-02-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/trc150094-a-novel-mitochondrial-modulator-reduces-cardio-metabolic-ris-peer-reviewed-fulltext-article-DMSO |
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| author | Joshi D GJ P Ghosh S Mohanan A Joshi S Mohan V Chowdhury S Dutt C Tandon N |
| author_facet | Joshi D GJ P Ghosh S Mohanan A Joshi S Mohan V Chowdhury S Dutt C Tandon N |
| author_sort | Joshi D |
| collection | DOAJ |
| description | Deepa Joshi,1 Prashant GJ,1 Shohini Ghosh,1 Anookh Mohanan,1 Shashank Joshi,2 Viswanathan Mohan,3 Subhankar Chowdhury,4 Chaitanya Dutt,1 Nikhil Tandon5 1Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India; 2Lilavati Hospital, Mumbai, India; 3Dr. Mohan’s Diabetes Specialities Centre (Madras Diabetes Research Foundation), Tamil Nadu, India; 4Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India; 5Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Deepa Joshi, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel + 91 7971315571, Email deepajoshi@torrentpharma.comBackground: TRC150094, a novel mitochondrial modulator, reduces insulin resistance and is expected to improve the trinity of dysglycemia, dyslipidemia, and hypertension. In this multi-dose phase-2 study, we evaluated the safety and efficacy of TRC150094 in diabetic subjects with dyslipidemia receiving standard of care.Methods: A randomized, multicenter, double-blind, placebo-controlled, parallel-group, Phase 2 study was conducted in 225 subjects from July 2013 to August 2015. The key inclusion criteria were body mass index of 23– 35 kg/m2, age between 30 and 65 years, fasting glucose of ≥ 126 or glycated hemoglobin (HbA1c) of ≥ 6.4% stabilized on treatment with ≤ 2 oral hypoglycemic agents, apolipoprotein-B (apo-B) ≥ 100 mg/dL, serum triglyceride (TG) ≥ 150 mg/dL, systolic blood pressure (SBP) ≥ 130 mmHg, and diastolic blood pressure (DBP) ≥ 85 mmHg with/without antihypertensive treatment. The subjects were randomly assigned to one of three TRC150094 doses (25, 50, or 75 mg) or placebo for 24 weeks. The outcomes assessed included fasting plasma glucose (FPG), insulin, mean arterial blood pressure (MAP), and apoB. In addition, safety and tolerability were assessed.Results: A reduction for dose up to 50 mg was noted for FPG in the range of 13.9 to 21.7 mg/dL (p < 0.05 for TRC150094 25 and 50 mg), fasting insulin reduction in the range 2.7 to 6.0 mU/L (all doses, p > 0.05), and improved HOMA-IR (− 2.0 to − 2.5) (all doses, p > 0.05) compared to placebo after 24 weeks of treatment. Furthermore, a significant reduction in MAP in the range 3.1 to 4.2 mmHg (p < 0.05 for TRC150094 25 and 75 mg) was noted. In addition, TRC150094 treatment was weight neutral, had a favorable effect on lowering atherogenic lipid fractions, including non-HDL cholesterol (− 6.8 mg/dL at 50 mg dose). Adverse events were mild to moderate in nature and not dose-related. One adverse event not related to treatment led to the discontinuation of the study. Overall, TRC150094 was safe and well tolerated for up to 24 weeks.Conclusion: In this study, TRC150094 treatment in the dose range of 25 to 50 mg showed improvement in various components of CMBCD, ie, dysglycemia, dyslipidemia, and hypertension.Trial Registration: This study was registered in the Clinical Trial Registry of India. Trial registration number: CTRI/2013/03/003444. Date of registration: 4th March 2013.Keywords: cardiometabolic-based chronic disease, mitochondrial modulator, type 2 diabetes, non-HDL cholesterol, hypertension, dyslipidemia |
| first_indexed | 2024-04-10T18:33:09Z |
| format | Article |
| id | doaj.art-72d2960f2a324ba2b53c0c887bfeaf9a |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T18:33:09Z |
| publishDate | 2022-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-72d2960f2a324ba2b53c0c887bfeaf9a2023-02-02T02:30:54ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072022-02-01Volume 1561563173241TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical TrialJoshi DGJ PGhosh SMohanan AJoshi SMohan VChowdhury SDutt CTandon NDeepa Joshi,1 Prashant GJ,1 Shohini Ghosh,1 Anookh Mohanan,1 Shashank Joshi,2 Viswanathan Mohan,3 Subhankar Chowdhury,4 Chaitanya Dutt,1 Nikhil Tandon5 1Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India; 2Lilavati Hospital, Mumbai, India; 3Dr. Mohan’s Diabetes Specialities Centre (Madras Diabetes Research Foundation), Tamil Nadu, India; 4Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India; 5Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Deepa Joshi, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel + 91 7971315571, Email deepajoshi@torrentpharma.comBackground: TRC150094, a novel mitochondrial modulator, reduces insulin resistance and is expected to improve the trinity of dysglycemia, dyslipidemia, and hypertension. In this multi-dose phase-2 study, we evaluated the safety and efficacy of TRC150094 in diabetic subjects with dyslipidemia receiving standard of care.Methods: A randomized, multicenter, double-blind, placebo-controlled, parallel-group, Phase 2 study was conducted in 225 subjects from July 2013 to August 2015. The key inclusion criteria were body mass index of 23– 35 kg/m2, age between 30 and 65 years, fasting glucose of ≥ 126 or glycated hemoglobin (HbA1c) of ≥ 6.4% stabilized on treatment with ≤ 2 oral hypoglycemic agents, apolipoprotein-B (apo-B) ≥ 100 mg/dL, serum triglyceride (TG) ≥ 150 mg/dL, systolic blood pressure (SBP) ≥ 130 mmHg, and diastolic blood pressure (DBP) ≥ 85 mmHg with/without antihypertensive treatment. The subjects were randomly assigned to one of three TRC150094 doses (25, 50, or 75 mg) or placebo for 24 weeks. The outcomes assessed included fasting plasma glucose (FPG), insulin, mean arterial blood pressure (MAP), and apoB. In addition, safety and tolerability were assessed.Results: A reduction for dose up to 50 mg was noted for FPG in the range of 13.9 to 21.7 mg/dL (p < 0.05 for TRC150094 25 and 50 mg), fasting insulin reduction in the range 2.7 to 6.0 mU/L (all doses, p > 0.05), and improved HOMA-IR (− 2.0 to − 2.5) (all doses, p > 0.05) compared to placebo after 24 weeks of treatment. Furthermore, a significant reduction in MAP in the range 3.1 to 4.2 mmHg (p < 0.05 for TRC150094 25 and 75 mg) was noted. In addition, TRC150094 treatment was weight neutral, had a favorable effect on lowering atherogenic lipid fractions, including non-HDL cholesterol (− 6.8 mg/dL at 50 mg dose). Adverse events were mild to moderate in nature and not dose-related. One adverse event not related to treatment led to the discontinuation of the study. Overall, TRC150094 was safe and well tolerated for up to 24 weeks.Conclusion: In this study, TRC150094 treatment in the dose range of 25 to 50 mg showed improvement in various components of CMBCD, ie, dysglycemia, dyslipidemia, and hypertension.Trial Registration: This study was registered in the Clinical Trial Registry of India. Trial registration number: CTRI/2013/03/003444. Date of registration: 4th March 2013.Keywords: cardiometabolic-based chronic disease, mitochondrial modulator, type 2 diabetes, non-HDL cholesterol, hypertension, dyslipidemiahttps://www.dovepress.com/trc150094-a-novel-mitochondrial-modulator-reduces-cardio-metabolic-ris-peer-reviewed-fulltext-article-DMSOcardiometabolic-based chronic diseasemitochondrial modulatortype 2 diabetesnon-hdl cholesterolhypertensiondyslipidemia. |
| spellingShingle | Joshi D GJ P Ghosh S Mohanan A Joshi S Mohan V Chowdhury S Dutt C Tandon N TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial Diabetes, Metabolic Syndrome and Obesity cardiometabolic-based chronic disease mitochondrial modulator type 2 diabetes non-hdl cholesterol hypertension dyslipidemia. |
| title | TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial |
| title_full | TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial |
| title_fullStr | TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial |
| title_full_unstemmed | TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial |
| title_short | TRC150094, a Novel Mitochondrial Modulator, Reduces Cardio-Metabolic Risk as an Add-On Treatment: a Phase-2, 24-Week, Multi-Center, Randomized, Double-Blind, Clinical Trial |
| title_sort | trc150094 a novel mitochondrial modulator reduces cardio metabolic risk as an add on treatment a phase 2 24 week multi center randomized double blind clinical trial |
| topic | cardiometabolic-based chronic disease mitochondrial modulator type 2 diabetes non-hdl cholesterol hypertension dyslipidemia. |
| url | https://www.dovepress.com/trc150094-a-novel-mitochondrial-modulator-reduces-cardio-metabolic-ris-peer-reviewed-fulltext-article-DMSO |
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