| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029883 |
| E.1.2 | Term | Obesity |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To confirm the added effect of acarbose in EMP16-120/40 on efficacy after a 26-week period of oral treatment compared with MR orlistat and orlistat in its conventional dosage form |
|
| E.2.2 | Secondary objectives of the trial |
Secondary efficacy objectives
• To compare the efficacy of MR orlistat with orlistat in its conventional dosage form after a 26-week period of oral treatment
• To explore the effect of a lower dose of EMP16-60/20 on efficacy after a 26-week period of oral treatment compared with placebo
Secondary safety and tolerability objectives
• To compare the added effect of acarbose in EMP16-120/40 on safety and tolerability during a 26-week period of oral treatment compared with MR orlistat
• To compare safety and tolerability of EMP16-120/40 with orlistat in its conventional dosage form during a 26-week period of oral treatment
• To compare the safety and tolerability of MR orlistat with orlistat in its conventional dosage form during a 26 week period of oral treatment
• To compare the safety and tolerability of EMP16-60/20 with placebo during a 26 week period of oral treatment
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study, potential participants must fulfil the following criteria:
1. Willing and able to give written informed consent for participation in the study.
2. Males or females (sex distribution 50:50, preferably ±5%) aged ≥18 years.
3. BMI ≥ 30 or ≥ 27 kg/m² in the presence of other risk factors based on participant interview e.g., hypertension (either or not treated with antihypertensive agents), glucose dysregulation (defined as elevated fasting glucose ≥6.1 mmol/L or HbA1c >42mmol/mol), T2DM that is treated with lifestyle changes (no medication allowed), and/or dyslipidemia (either or not treated with antihyperlipidemic agents). If indicated, plasma/serum total cholesterol, LDL, HDL, and/or TGs can be measured to verify eligibility as judged by the Investigator.
4. No clinically significant abnormalities regarding physical examination, vital signs, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.
5. Adequate renal function: creatinine <1.5 times upper limit of normal (ULN).
6. Adequate hepatic function: AST, ALT, ALP and GGT <2.5 times ULN and bilirubin <1.5 times ULN.
|
|
| E.4 | Principal exclusion criteria |
Potential participants must not enter the study if any of the following exclusion criteria are fulfilled:
1. Weight unstable (≥ 5% reported change during the previous 3 months) preceding screening and randomization.
2. Subjects who are pregnant, who are currently breastfeeding, who intend to become pregnant within the period of the study, or who gave birth within the 6 months preceding the screening visit.
3. T2DM treated with medication.
4. History or presence of any clinically significant disease, disorder, or history of surgery which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant’s ability to participate in the study including but not limited to:
• GI problems/diseases, e.g., diseases that affect intestinal absorption and peristalsis such as inflammatory bowel diseases, irritable bowel syndrome (IBS) and Hirschsprung’s disease
• Cholestasis
• Chronical malabsorption syndrome
• Severe allergic, cardiac, or hepatic disease
• Previous GI surgery that might influence GI function significantly, such as previous bariatric surgery, and previous gallbladder surgery as judged by the investigator.
Potential participants with well-treated chronic diseases (e.g., celiac disease and lactose intolerance) may be included in the study at the discretion of the Investigator.
5. Significant clinical illness within the preceding 2 weeks of the first administration of IMP at the discretion of the Investigator.
6. Any significant medical/surgical procedure or trauma within 4 weeks of the first administration of IMP at the discretion of the Investigator.
7. Any planned major surgery within the duration of the study.
8. Any use of drugs altering glucose metabolism and drugs used for diabetes (A10A and A10B) or drugs that are affected by, or that affect, orlistat and acarbose, within 2 weeks prior to the first administration of IMP.
9. Regular use of prescribed or non-prescribed medication within 2 weeks prior to the first administration of IMP as judged by the Investigator. Patients who are on stable treatment with anti-depressants (e.g., selective serotonin re-uptake inhibitors [SSRI]) for at least 2 months can be included at the discretion of the Investigator.
10. Untreated high blood pressure (systolic blood pressure >160 mmHg and diastolic blood pressure >100 mmHg at the screening visit).
11. Known hypersensitivity to any of the test substances.
12. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
13. Excessive intake of alcohol, as judged by the Investigator.
14. Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse.
15. Positive screen for drugs of abuse, or positive screen for alcohol, at the screening visit (Visit 1).
16. Any positive result at the screening visit (Visit 1) for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
17. Plasma donation within 1 month of the screening visit (Visit 1) or any blood donation (or corresponding blood loss) during the 3 months prior to the screening visit.
18. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 3 months of the first administration of IMP in this study. Participants consented and screened but not dosed in previous studies are not excluded.
19. Investigator considers the potential participant unlikely to comply with study procedures, restrictions, and requirements.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Co-primary endpoints
• Relative (%) change from baseline in body weight at week 26
• Proportion of participants with ≥5% decrease in body weight at week 26
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints
• Relative (%) change from baseline in body weight at week 26 (secondary and exploratory comparisons)
• Proportion of participants with ≥5% (secondary and exploratory comparisons) and ≥10% (all comparisons) decrease in body weight at week 18 and week 26
• Absolute change from baseline in body weight at week 26
• Relative (%) and absolute change from baseline in body weight during the 26-weeks treatment period
• Absolute change from baseline in body mass index (BMI)
• Absolute change from baseline in waist circumference
• Absolute change from baseline in sagittal diameter
• Absolute change from baseline in percentage body fat
• Absolute change from baseline in Quality of life (Rand-36 and EQ-5D-5L)
• Absolute change from baseline in lifestyle (diet, sleep, and physical activity)
• Absolute change from baseline in fasting hemoglobin A1c (HbA1c), glucose, insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), high sensitivity C-reacting protein (hs-CRP) and albumin
• Absolute change from baseline in Visceral adiposity index (VAI), Fatty liver index (FLI) and homeostatic model assessment (HOMA) index
• Absolute change from baseline in blood pressure and heart rate
Secondary safety & tolerability endpoints
• Tolerability, assessed by conventional adverse event (AE) reporting (with special focus on oily spotting and fecal incontinence)
• Number of withdrawals from study (total and gastrointestinal [GI] related)
• Absolute change from baseline in fasting liver enzymes
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| According to study flowchart |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last Patient Last Visit (LPLV) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
Print
