This study is a proof of concept study to demonstrate that EMP16-02, a fixed dose combination (FDC) of orlistat and acarbose in an oral multiple-unit modified release (MR) formulation leads to a clinically relevant decrease in body weight. The study aims to evaluate the efficacy, safety and tolerability of treatment with two different doses of EMP16 02 (120 mg orlistat/40 mg acarbose and 150 mg orlistat/50 mg acarbose) for 26 weeks on reducing body weight in obese patients.
EMP16-02 will be given to obese patients with an initial BMI ≥ 30 kg/m² or ≥ 28 kg/m² in the presence of other risk factors (e.g., hypertension, glucose dysregulation such as impaired glucose tolerance and type 2 diabetes mellitus (T2DM) and/or dyslipidaemia.
The study consists of 6 visits to the research clinic, including screening and follow-up. There will be no overnight stays at the clinic.
Visit 1: Screening (Visit 1) will take place from Day -28 to Day -1. Visit 2: Eligible and consenting patients will arrive at the research clinic in the morning of the first dosing day (Day 1, Visit 2) after at least 8 hours overnight fasting.
A re-check of eligibility including a brief physical examination, vital signs and assessment of body weight will be conducted. The patients will be randomised to either of two doses of EMP16-02 or placebo:
1. EMP16-02 120 mg O/40 mg A
2. EMP16-02 150 mg O/50 mg A
3. Placebo (identical capsules) Blood sampling (fasting), and anthropometric measurements will be performed. Patients will receive electronic diary instructions and will be asked to fill in a satiety and craving questionnaire before breakfast (at the clinic), and then once every hour for 4 hours until before lunch (at home). A standardised breakfast will be served at the clinic. Halfway through breakfast at Visit 2, all patients will receive a placebo capsule independent of the treatment arm to which the patients have been randomised, to provide patients with the opportunity to train on self administering the Investigational Medicinal Product (IMP) under supervision of clinic staff. The patients will also receive instructions for filling in more questionnaires regarding health and quality of life, meal pattern, activity and sleep, and gastrointestinal symptoms (gastrointestinal rating scale \[GSRS\]). The patients will be instructed to take EMP16-02 or placebo halfway through each meal, together with approximately 100-200 mL water (or other drink) on all subsequent treatment days. Once IMP has been handed out, the patients are free to leave the clinic. The first randomised IMP dose will be taken during lunch (or the next meal) at home.
Between visit 2 and 3: Patients randomised to EMP16-02 will start with a run-in period of 6 weeks during which the dose is sequentially increased. From week 7, all patients will have reached their final intended dose and a 20 week treatment and observation period will start. The run-in phase will start at a dose of 60 mg O and 20 mg A TID, which will sequentially be increased with 30 mg O/10 mg A every two weeks until the target doses of 120 mg O/40 mg A TID (for the lower dose group) and 150 mg O/50 mg A TID (for the higher dose group) are reached. Placebo treatment consists of matching oral capsules. Placebo and EMP16-02 capsules need to be taken TID together with three daily meals.
Visit 3-5: Patients will come to the clinic at Visit 3 (week 7), Visit 4 (week 14) and Visit 5 (week 26) for safety assessments and assessments of weight and anthropometric measurements. Patients will arrive in the morning after at least 8 hours overnight fasting. All visits will start with a brief physical examination followed by blood sampling (fasting) and assessment of body weight and body composition. A standardised breakfast will be served during which the patient will take the IMP. All or a selection of the questionnaires, including the satiety and craving questionnaire, will be filled in in a similar way as during Visit 2.
New IMP will be handed out to the patients at Visit 2, 3 and 4. At Visit 5 (week 26), the patients will take the last dose during breakfast at the clinic.
After 18 and 22 weeks of treatment (Day 123 ± 3 days and Day 151 ± 3 days, respectively), patients will be asked to answer questions about IMP compliance, occurrence of adverse events (AEs) and use of concomitant medication using an electronic diary.
Visit 6: A follow up safety visit.
