| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 |
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| 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 evaluate the effect of the study drug EMP16-02 (120 mg orlistat [O]/40 mg acarbose [A]) on relative body weight loss after a 26-week period of oral treatment as compared to placebo. |
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| E.2.2 | Secondary objectives of the trial |
•Assess effect of two doses of EMP16-02 on relative and absolute body weight loss during 26-weeks as compared to placebo.
• Assess effect of two doses of EMP16-02 on other anthropometric characteristics during 26-weeks as compared to placebo.
• Assess effect of two doses of EMP16-02 on satiety and meal pattern during 26-weeks as compared to placebo.
• Assess effect of two doses of EMP16-02 on fasting insulin, glucose metabolism markers, lipid metabolism markers and inflammation markers during a 26-weeks as compared to placebo.
• Assess effect of two doses of EMP16-02 on blood pressure during 26-weeks as compared to placebo.
• Assess effect of two doses of EMP16-02 on quality of life during 26-weeks as compared to placebo.
• Assess relationship between drop-out(s) and tolerability for two different doses of EMP16-02 during 26-weeks as compared to placebo.
• Assess safety and GI tolerability of two different doses of EMP16-02 during a26-weeks as compared to placebo.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Willing and able to give written informed consent for participation in the study.
2. Aged ≥ 18 and ≤ 75 years.
3. Maximum weight of 150 kg and BMI ≥ 30 or ≥ 28 kg/m² in the presence of other risk factors based on patient interview, e.g., hypertension (either or not treated with antihypertensive agents), glucose dysregulation such as impaired glucose tolerance (defined as elevated fasting glucose as judged by the Investigator) and T2DM that is treated with life style changes (no medication allowed), and/or dyslipidaemia (either or not treated with antihyperlipidemic agents). If indicated, plasma/serum total cholesterol, LDL, HDL, and triglycerides can be measured to verify eligibility as judged by the Investigator.
4. Acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
5. Adequate renal and hepatic function as judged by the Investigator in accordance with the expected disease profile
6. Weight stable (<5% reported change during the three months preceding screening), based on patient interview and weight assessments at screening (Visit 1) and randomisation (Visit 2).
7. Willing to eat three meals per day, and willing to eat breakfast during the visits to the clinic.
8. Males and females may be included in the study. WOCBP must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD]or intrauterine hormone-releasing system [IUS]) OR practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the patient) from at least 4 weeks prior to first dose to 4 weeks after last dose.
Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or post menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with simultaneous detection of follicle stimulating hormone [FSH] 25 140 IE/L).
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| E.4 | Principal exclusion criteria |
1. T2DM treated with medication.
2. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient’s ability to participate in the study.
3. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks prior to the first administration of IMP, at the discretion of the Investigator.
4. Any planned major surgery within the duration of the study.
5. Untreated high blood pressure (systolic blood pressure [SBP] > 160 mmHg and diastolic blood pressure [DBP] >100 mmHg at screening).
6. Use of any of the prohibited medication listed in Table 9.6 1 within 2 weeks prior to the first administration of IMP. Recently started use of anti-depressants (e.g., selective serotonin re-uptake inhibitors [SSRI]) within 2 weeks prior to the first IMP administration or planned start of anti-depressant treatment during the study period is not allowed, yet patients that are on stable treatment with anti-depressants for at least two months can be included.
7. Known hypersensitivity to any of the test substances. History of hypersensitivity to drugs with a similar chemical structure or class to orlistat and acarbose.
8. Gastrointestinal problems/diseases, e.g., inflammatory bowel diseases and Irritable Bowel Syndrome (IBS). Untreated gastroesophageal reflux disease (GERD) or GERD that is treated occasionally is allowed as judged by the Investigator.
9. Cholestasis.
10. Previous gastrointestinal surgery that might influence gastrointestinal function significantly, previous bariatric surgery, and previous gallbladder surgery as judged by the investigator.
11. Known vitamin B12 deficiency or other signs of achlorhydria.
12. Chronical malabsorption syndrome.
13. Clinically significant abnormal laboratory values at screening as judged by the investigator.
14. History of severe allergic, cardiac or hepatic disease. History of significant cardiovascular disease such as myocardial infarction, congestive heart failure, stroke, serious cardiac arrhythmias. History of angina within 6 months prior to screening.
15. A personal or family history of Medullary Thyroid Carcinoma (MTC).
16. A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
17. Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse, as judged by the Investigator.
18. Positive screen for drugs of abuse at screening or admission to the clinic or positive screen for alcohol at screening or admission to the clinic prior to administration of the IMP.
19. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV.
20. Plasma donation within one month of screening or any blood donation (or corresponding blood loss) during the three months prior to screening.
21. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study that included drug treatment within three months of the first administration of IMP in this study. Patients consented and screened but not dosed in previous studies are not excluded.
22. Investigator considers the patient unlikely to comply with study procedures, restrictions and requirements.
23. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
24. Prolonged QTcF (>450 ms for males, >470 for females), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
25. Patients with swallowing disorders, which may affect the patient’s capability to swallow the IMP.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Relative (%) change from baseline in body weight after 26 weeks of treatment with EMP16 02 (120 mg O/40 mg A) as compared to placebo. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
• Absolute change from baseline in body weight after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A) as compared to placebo.
• Relative (%) and absolute change from baseline in body weight after 14 and 26 weeks of treatment with EMP16-02 (150 mg O/50 mg A) as compared to placebo.
• Proportion of patients with ≥5% and ≥10% decrease in body weight compared to baseline after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Relative (%) and absolute change from baseline in body mass index (BMI) after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Absolute change from baseline in waist circumference after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Absolute change from baseline in sagittal diameter after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Relative (%) and absolute change from baseline in percentage body fat after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Satiety and craving after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo, corrected for satiety and craving after standardised breakfast at baseline.
• Relative (%) and absolute change from baseline in fasting haemoglobin A1c (HbA1c), glucose, insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, liver enzymes, albumin and high-sensitivity C-reactive protein (hs CRP) after 7, 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Change from baseline in the proportion of diabetic (fasting glucose ≥ 7.0 mmol/L) and prediabetic patients (fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L) after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Relative (%) and absolute change from baseline in blood pressure after 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Change from baseline in quality of life after 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Dropout rate (overall and GI-related) following treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Frequency and severity of adverse events (AEs) during 26 weeks of treatment with EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Clinically significant relative (%) and absolute changes from baseline in safety laboratory parameters and ECG after 26 weeks of treatment, and in vital signs after 7, 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• GI tolerability after 2, 4, 6, 8, 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo.
• Compliance after 7, 14 and 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A) as compared to placebo
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| According to study flowchart. |
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| 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 | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 2 |
| 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
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| Last Patient Last Visit (LPLV) |
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| 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 | 18 |
| E.8.9.1 | In the Member State concerned days | |
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