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MATCHED Trial
" While medical guidelines recommend stringent blood pressure targets for diabetic patients, such as those studied in the MATCHED trial, achieving and maintaining these targets has proven to be extremely difficult. Although all classes of antihypertensive agents are effective at lowering blood pressure in diabetic patients, treatment has been further complicated by the fact that some major classes have been shown to have deleterious effects on glycemic control. The results from MATCHED demonstrate that MC-4232 not only provides clinically important blood pressure reduction beyond that of lisinopril alone, but also improves upon the glycemic and lipid control offered by current therapies. Based on this data, I believe MC-4232 could be an innovative new treatment that in addition to significant blood pressure reduction also offers metabolic benefits to patients with coexisting diabetes and hypertension.” - Yves Lacourci¸re MD, FRCP, FACP, Principle Investigator, MATCHED study, and Professor of Medicine, Laval University
Results from Blood Pressure Endpoints:
The results of MATCHED demonstrate the positive clinical effects of MC-4232 on primary and secondary blood pressure endpoints, including both systolic and diastolic measurements:
- The 300mg/20mg (MC-1/lisinopril) dose of MC-4232 had a statistically significant reduction of 12.0 mmHg (p<0.0001) from baseline over 8 weeks on the primary endpoint of mean daytime ambulatory systolic blood pressure (MDASBP).
- The 300mg/20mg dose of MC-4232 reduced MDASBP by 12.0 mmHg over 8 weeks as compared to a 7.5 mmHg reduction with lisinopril alone, equating to an additional 4.5 mmHg (p=0.13) reduction, demonstrating the improved antihypertensive effects of MC-4232 over lisinopril alone.
- In the secondary endpoint of reduction in mean daytime ambulatory diastolic blood pressure (MDADBP), the 300mg/20mg dose of MC-4232 reduced MDADBP by 7.5 mmHg over 8 weeks as compared to a 4.1 mmHg reduction with lisinopril alone, equating to an additional 3.4 mmHg (p=0.06) reduction, again demonstrating the improved antihypertensive effects of MC-4232 over lisinopril alone.
Results from Metabolic Endpoints:
The results of MATCHED also demonstrated the positive clinical effects of MC-4232 on primary and secondary metabolic endpoints, including glycemic control as measured by fasting serum glucose and glycated hemoglobin (HbA1c), as well as lipid control, after 16 weeks of treatment.
- The 300mg/20mg dose had a statistically significant reduction of 1.45 mmol/L (p=0.026) versus placebo on the primary endpoint of fasting serum glucose.
- In those patients with HbA1c greater than the prespecified level of 8.0%, the 300mg/20mg dose had an absolute reduction of 0.63% (p=0.27) compared to placebo. This exceeds the regulatory requirements in HbA1c reduction of ≥0.40% for antidiabetic therapeutics. The majority of the patients in the study were well controlled with current antidiabetic therapy, with less than 19% exceeding 8.0% HbA1c.
- In those patients with elevated triglycerides (>1.7mmol/L), the 300mg/20mg dose of MC-4232 provided a statistically significant reduction of triglyceride levels by .70 mmol/L (p=0.04) versus baseline.
On all key metabolic and blood pressure endpoints the 300mg/20mg and 1000mg/20mg doses of MC-4232 demonstrated comparable clinical efficacy. The study results also demonstrated that MC-4232 was safe and well tolerated at all dose levels.
Study Design
The MATCHED study ( MC-1 and ACE Therapeutic Combination for Hypertensive Diabetics) was designed as a Phase II trial to determine the optimal dose and endpoint for Phase III development of MC-4232. MATCHED was a randomized, parallel group, cross-over, double-blind, placebo-controlled comparison of 100, 300 or 1000 mg of MC-1 alone and in combination with 20 mg of lisinopril. The study results are based on a population of 120 patients with coexisting type II diabetes and hypertension from 12 sites across Canada. In order to minimize the carry-over effects of lisinopril, all patients were randomized in two different treatment sequences. Patients randomized in the first treatment sequence received an 8-week treatment with MC-4232 (20 mg of lisinopril and MC-1) or placebo and then an 8-week treatment with MC-1 alone or placebo. Patients randomized in the second treatment sequence received an 8-week treatment with MC-1 alone or placebo and then an 8-week treatment with MC-4232 or placebo. In each treatment sequence, all patients were randomized to MC-1 at one of the three prespecified dosages.
This trial was conducted under the guidance and direction of the internationally recognized hypertension specialist, Yves Lacourcière, MD, FRCP, FACP, Director of the Hypertension Research Unit, Centre Hospitalier de l'Université Laval Sainte-Foy, Québec. Dr. Lacourcière, one of North America's foremost experts in management of hypertension in difficult to treat patient groups, led a group of specialist investigators who enrolled patients at sites across Canada. Dr. Lacourcière has led numerous important hypertension studies and serves as a scientific advisor to several leading pharmaceutical companies.
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