Study design

This was a single-centre, controlled, randomized, parallel group phase IIa study with the primary objective to evaluate the effect after two weeks’ treatment with three different dose combinations of the test formulation EMP16-01 on appetite/tolerability score, as compared to Xenical®, measured by questionnaires. The dose combinations (in mg) tested were (orlistat/acarbose) 60/20, 90/30 and 120/40. A total of 67 subjects with a mean age of 42.9 years and a mean BMI of 34.7 kg/m2 were included and treated, divided into four study arms. Sixty-four (64) subjects completed the study.

Clinical results

The first phase IIa trial of EMP16-01has demonstrated best-in-class safety profile and a potentially improved effect as compared to Xenical. The results clearly indicate that EMP16-01 has a stronger appetite suppressing effect than Xenical. EMP16-01 also had a significant effect on GIP, an incretine, demonstrating superior glycaemic control , which is reflected in plasma insulin and glucose levels. The appetite supressing effect, the improved glycaemic control and the reduced energy uptake (the last item as a consequence of the traditional orlistat effect) clearly indicates that a 7% weight reduction as compared to baseline after one year treatment is feasible. Altogether, EMP16-01 has the clinical potential to be a safe and effective treatment for obese persons both with and without a reduced glucose control.

Due to its excellent safety profile, overweight subjects with or without decreased glucose tolerance, i.e. “pre-diabetic” and/or “pre-obese”, could be especially interesting as a treatment group as there are currently no relevant (and safe) alternative products available.

 

Effect

The hunger ratings were reduced in more subjects during 14 days for the EMP16-01 120/40 treatment group compared with the Xenical® treatment group. This observation is in line with the proposed gastrointestinal brake effect of EMP16-01. In this two weeks study, there was no statistically significant higher body weight reduction (EMP16-01 120/40; -1.3 kg and Xenical®; -1.6 kg). Hhowever, the observed weight reduction, in combination with the higher reduced appetite, suggests that a more pronounced weight reduction can be expected during a long-term study with EMP16 than with Xenical®.

Safety and tolerability

The GI absorption and systemic availability of orlistat was lower for all three doses of EMP16-01 compared to Xenical®. This indicates that the safety of EMP16-01 is at least good as Xenical® regarding systemic effects, side-effects and drug-drug interactions.

EMP16-01 also has a better tolerability than Xenical regarding several compliance related side effects such as oily and liquid stools, oily spottings as well as faecal incontinence. It is clear from this study that the suspected augmented GI originated side effects form the orlistat and acarbose combination is tethered by the novel modified release properties of EMP16-01. The only question where EMP16-01 scored worse than Xenical® was faecal urgency and this difference was only apparent during the first few days of treatment.

The proportion of subjects experiencing any TEAE increased with increasing orlistat/acarbose dose (18-69%), as compared to 65% of subjects treated with Xenical®. Five of the nine cases of headache (55.6%) were assessed as possibly related to study treatment; two occurred during treatment with EMP16-01 90/30, one during treatment with EMP16-01 120/40 and two were related to Xenical®.