BGP-15 Clinical Trials

N-Gene has conducted three clinical studies to demonstrate the safety of BGP-15, and to explore the metabolic effects on human subjects which are insulin resistant due to obesity or treatment with anti-schizophrenic drugs.

BGP-15, Phase I
Single escalating doses of BGP-15 up to 800 mg, and repeated doses of 250 mg and 600 mg BGP-15, have been shown to be well tolerated

BGP-15, Phase IIa Study In Obese, Insulin Resistant Subjects
The central goal of this study was to determine the putative insulin sensitizing effect of BGP-15 on subjects with insulin resistance, assessed by the "hyperinsulinemic euglycemic clamp" technique. In this gold standard methodology, the mount of glucose is determined which needs to be given intravenously to the study subjects to compensate for a fixed dose of injected insulin. Insulin sensitive (healthy) subjects will need more glucose than insulin resistant subjects.

In this 3-arm, double blind, placebo controlled clinical study, conducted over a period of 28 days, subjects where dosed orally once every day with either placebo, 200mg/day of BGP-15 or 400 mg/day of BGP-15. For each study participant, insulin sensitivity was determined at study beginning and study end. The treatment effect in each individual is expressed as the difference, as change from baseline. Mean and standard deviation for change from baseline insulin sensitivity is then calculated in each arm.

It could be demonstrated that the primary efficacy parameter insulin sensitivity was significantly improved after each dose of 28 day BGP 15 treatment. The higher dose was more efficient, but differences were not statistically significant. Exploratory, secondary endpoint such as blood lipids also changed in a beneficial way upon BGP-15 treatment.



BGP-15, Phase Ia Study In Insulin Resistant Subjects Treated With Olanzapine
Insulin resistance and weight gain, as induced by anti-schizophrenic drugs, constitute a major health risk and a central impediment to patient compliance.

In order to explore the utility of BGP-15 as an adjunct to anti-schizophrenic drugs, N-Gene sponsored a study with the objective i) to determine the pharmacokinetic properties of BGP-15 and olanzapine co-administration, and ii) to measure the effect of BGP-15 on the olanzapine-induced insulin resistance.

In this double blind, placebo controlled study, 54 healthy volunteers received once-a-day olanzapine (10 mg dose) and either, a daily dose of 400 mg BGP-15 (b.i.d., 200mg + 200mg) or placebo. At baseline, and following a 17 d treatment plus a washout period of 1 week, insulin sensitivity in study subjects was determined with the "hyperinsulinemic euglycemic clamp" methodology. Then, the change of insulin sensitivity from baseline was calculated for the BGP-15 and the placebo treated arm (-> methodology as in "BGP-15, Phase IIa study in obese, insulin resistant subjects").

As a key result, an insulin-sensitizing effect could be demonstrated for BGP-15 also in this setting of insulin resistance, such that the placebo treated patients deteriorated much stronger in their insulin sensitivity than the BGP-15 treated subjects.
 

Insulin sensitivity, change from baseline, per total body mass

While a definitive assessment of BGP-15´s effectiveness as an adjunct in this indication can only be based on studies with a longer duration in schizophrenia patients, the study presented here provides mechanistic evidence that BGP-15 is targeting a central pathway of insulin resistance which appears to be common to states of obesity and drug treatment with anti-schizophrenics.