A Proof of Concept Trial in Overweight and Obese Patients, Investigating Effect of EMP16-02 on Body Weight (Primary)
Condition: Overweight or Obesity
MeSH terms: Overweight; Body Weight
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): EMP16-02 120 mg orlistat/40 mg acarbose; EMP16-02 150 mg orlistat/50 mg acarbose; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): EMP16-02 capsules are composed of three pharmaceutical fractions (granules denoted G1, G2 and G3). G1= Prolonged release of acarbose, G2= Enteric-coated granule fraction containing orlistat and acarbose, G3= Orlistat with a delayed on-set release mechanism.; EMP16-02 capsules are composed of three pharmaceutical fractions (granules denoted G1, G2 and G3). G1= Prolonged release of acarbose, G2= Enteric-coated granule fraction containing orlistat and acarbose, G3= Orlistat with a delayed on-set release mechanism.; Matching oral placebo capsules
Other intervention name(s): 120 mg O/40 mg A; 150 mg O/50 mg A
Intervention MeSH terms: Acarbose; Orlistat
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is an exploratory, randomised, double-blind and placebo-controlled study.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Overweight; Obesity; Orlistat; Acarbose