PC-DAC(TM):Exendin-4 Phase I/II Multiple-Dose Study Preliminary Results Demonstrate Safety and Efficacy at Once-Weekly Dosing
One Month Study in Seventy Type 2 Diabetes Patients
MONTREAL, March 26 /CNW/ - ConjuChem Biotechnologies Inc. (TSX:CJB) today
announced positive preliminary results from its Phase I/II multiple-dose
clinical study for the treatment of Type 2 diabetes using the Company's
proprietary PC-DAC(TM):Exendin-4. Results from the study demonstrated that
PC-DAC(TM):Exendin-4 was generally well tolerated and, when administered
once-weekly at each of the dosing levels tested, lowered blood glucose.
The Phase I/II trial, a randomized, double-blind, multiple-dose study,
evaluated safety and tolerability of PC-DAC(TM):Exendin-4 in patients with
stable Type 2 diabetes. Pharmacokinetic and pharmacodynamic parameters were
also evaluated. All patients were on stable doses of metformin with HbA1c
levels between 7.0% and 10.6%. The trial enrolled 70 patients at 7 centers in
the U.S. and Canada with patients randomized to one of four parallel treatment groups: 1 mg (n=18), 2 mg (n=17), 3 mg (n=17) or placebo (n=18). Sixty-nine
patients received 5 doses over a one month period. The product is a highly soluble liquid formulation injected with a 30 gauge needle.
Reductions in mean fasting plasma glucose (FPG) were statistically
significant in all treatment groups versus baseline and placebo over the
five-week treatment period (FPG was measured Days 1 and 7 post-dosing). The
average reductions from baseline values for the 1 mg, 2 mg, and 3 mg treatment
arms were -9% (baseline 154 mg/dL), -11% (baseline 172 mg/dL), and -7%
(baseline 170 mg/dL), respectively, versus -1% (baseline 158 mg/dL) in the placebo group. The reductions were statistically significant versus baseline (p(less than)0.005 for all cohorts) and versus placebo (p(less than)0.005 for 1mg and 2 mg cohorts, p(less than)0.03 for the 3 mg cohort).
HbA1c improved in all three treatment groups with median HbA1c decreasing
0.5%, 0.8%, and 0.6% in the 1 mg, 2 mg, and 3 mg groups at the end of the
five-week period, decreasing 0.7%, 0.6%, and 0.7% at day 49, and decreasing
0.7%, 0.8%, and 0.9% at the end of the study period (day 63) versus baseline.
The placebo group declined 0.35% at five weeks, 0.3% at day 49, and 0.2% at
the end of the study period. The reduction for the pooled treatment groups was statistically significant versus placebo at day 49 and at the end of the study period (p(less than)0.03, ANCOVA).
There was no statistically significant effect on weight in the treatment cohorts versus baseline or placebo at the end of the 35-day treatment period. The drug was generally well tolerated. The most common side effects during treatment included headache occurring in 3 out of 18 placebo patients (17%) and 15 out of 52 treated patients (29%) and nausea which was reported in
3 out of 18 placebo patients (17%) and 11 out of 52 treated patients (21%). There were no cases of drug-related vomiting in either the 1 mg or 2 mg cohorts; vomiting occurred in 5 patients in the 3 mg cohort, none of which led to patient drop-out. There were no skin reactions in the 2 mg and 3mg treatment groups; skin reactions were reported in 4 placebo patients and 1 patient in the 1mg cohort. Generally low-level antibodies were detected in 11 out of 52 treated patients (21%). There were no drug-related serious adverse
events during the study.
Commenting on these preliminary results, Thomas Ulich, M.D., ConjuChem's
Executive Vice President of Research and Development, stated: "These
encouraging results provide evidence that long-term once-weekly administration
of PC-DAC(TM):Exendin-4 can be therapeutically useful for control of glycemia
in patients with Type 2 diabetes. In particular, the study demonstrated that
treatment with 2 mg of PC-DAC(TM):Exendin-4 was very well tolerated and effective in lowering blood glucose levels." ConjuChem intends to submit the study results for presentation at a scientific meeting in 2007. In conjunction with the multi-dose results, ConjuChem also reported that ongoing product development programs including manufacturing process improvements are expected to be completed in 2007 in time to be included in a Phase II study, which is planned for initiation by year-end.
Exendin-4 is a Glucagon-like peptide-1 (GLP-1) homolog and an agonist for
the GLP-1 receptor. Exendin-4 decreases glucagon and increases insulin
secretion in a glucose-dependent manner. Exendin-4 may stimulate beta-cell
proliferation, restore beta-cell sensitivity to glucose, delay gastric
emptying, and increase peripheral sensitivity to glucose. The clinical utility
of Exendin-4 is somewhat limited by its relatively short half-life in plasma. Developed with ConjuChem's proprietary PC-DAC(TM) technology, PC-DAC(TM):Exendin-4 is a modified Exendin-4 analogue that is covalently bound to recombinant human albumin (Recombumin(R), provided by Novozymes Delta Limited). The preformed albumin-peptide conjugate has a much longer half-life
than the peptide alone. The product is a highly soluble liquid formulation that is injectable in a small volume with a small gauge needle.