A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin.

Curcumin, the bioactive component of turmeric, Curcuma longa has an exceptionally wide spectrum of activities including antioxidant, anti-inflammatory and anti-cancer properties, and is currently under different phases of clinical trials for various types of soft tissue cancers. However, although in vitro and animal studies have shown anticancer activities of curcumin for virtually all types of human cancers, its poor bioavailability in the human body has severely limited its application to these diseases. Methods to increase its oral bioavailability are a subject of intense current research. Reconstituting curcumin with the non-curcuminoid components of turmeric has been found to increase the bioavailability substantially. In the present clinical study to determine the bioavailability of curcuminoids, a patented formulation, BCM-95((R))CG was tested on human volunteer group. Normal curcumin was used in the control group. Curcumin content in blood was estimated at periodical intervals. After a washout period of two weeks the control group and drug group were crossed over BCM-95((R))CG and curcumin, respectively. It was also compared with a combination of curcumin-lecithin-piperine which was earlier shown to provide enhanced bioavailability. The results of the study indicate that the relative bioavailability of BCM-95((R))CG (Biocurcumax) was about 6.93-fold compared to normal curcumin and about 6.3-fold compared to curcumin-lecithin-piperine formula. BCM-95((R))CG thus, has potential for widespread application for various chronic diseases.

Efficacy, dose-response relationship and safety of once-daily extended-release metformin (Glucophage XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double-blind, placebo-controlled studies.

AIM: The efficacy, dose-response relationships and safety of an extended-release formulation of metformin (Glucophage) XR) were evaluated in two double-blind, randomized, placebo-controlled studies of 24 and 16 weeks' duration, in patients with inadequate glycaemic control despite diet and exercise. Protocol 1 provided an evaluation of metformin XR at a commonly used dosage. Protocol 2 evaluated different dosages of metformin XR. METHODS: In Protocol 1, 240 patients were randomized to receive metformin XR 1000 mg once daily. or placebo in a 2:1 ratio for 12 weeks (patients could receive metformin XR 1500 mg during weeks 12-24 if required). In Protocol 2, 742 patients were randomized to receive metformin XR 500 mg once daily, 1000 mg once daily, 1500 mg once daily, 2000 mg once daily, 1000 mg twice daily or placebo for 16 weeks. The primary endpoint in each study was the change from baseline in HbA(1C) at 12 weeks (Protocol 1) or 16 weeks (Protocol 2). RESULTS: Metformin XR reduced HbA(1C) in Protocol 1, with mean treatment differences for 1000 mg once daily vs. placebo of -0.7% at 12 weeks and -0.8% at 24 weeks (p < 0.001 for each). In Protocol 2, a clear dose-response relationship was evident at doses up to 1500 mg, with treatment differences vs. placebo of -0.6% (500 mg once daily), -0.7% (1000 mg once daily), -1.0% (1500 mg once daily) and -1.0% (2000 mg once daily). The efficacy of metformin XR 2000 mg once daily and 1000 mg twice daily were similar (mean treatment differences vs. placebo in HbA(1C) were -1.0% and -1.2%, respectively). More patients achieved HbA(1C) < 7.0% with metformin XR vs. placebo in Protocol 1 (29% vs. 14% at 12 weeks) and with once-daily metformin XR in Protocol 2 (up to 36% vs. 10% at 16 weeks). No significant changes in fasting insulin or body weight occurred. Total and low-density lipoprotein (LDL)-cholesterol improved (p < 0.05-p < 0.001) in metformin XR groups in Protocol 2. Metformin XR was well tolerated; gastrointestinal side effects were more common with metformin XR vs. placebo, but few patients withdrew for this reason (1.3% vs. 1.3% in Protocol 1 and 1.6% vs. 0.9% in Protocol 2). CONCLUSIONS: Once-daily metformin XR presents an effective and well-tolerated therapeutic option for delivering metformin in a convenient manner, which supports good compliance with therapy.

Durable efficacy of metformin/glibenclamide combination tablets (Glucovance) during 52 weeks of open-label treatment in type 2 diabetic patients with hyperglycaemia despite previous sulphonylurea monotherapy.

Oral anti-diabetic combinations that address insulin resistance and beta-cell dysfunction (e.g. metformin and glibenclamide) represent a rational therapeutic option for patients uncontrolled on monotherapy. A 52-week, open-label extension to a double-blind study evaluated metformin-glibenclamide combination tablets (Glucovance) in 477 patients with hyperglycaemia despite sulphonylurea therapy. Reductions in HbA1C were maintained, with a mean reduction of -1.7% after 52 weeks, compared with the baseline value for the double-blind trial. Eighty-five patients receiving 4 x 500 mg/2.5 mg tablets daily displayed a marked improvement in HbA1c following up-titration to a regimen of 2 x 500 mg/2.5 mg + 3 x 500 mg/5 mg tablets. Lipid profiles improved significantly. The combination tablets were well tolerated: 11.1% of patients reported hypoglycaemic symptoms (all either mild or moderate severity). No patient withdrew or required pharmacologic intervention for hypoglycaemia. Metformin-glibenclamide combination tablets are an effective and well-tolerated therapeutic option for intensifying oral anti-diabetic therapy.