A PilOt Dose-escalation Trial With EMP16 in Preparation for Phase III - the POEM Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 39
- 主要终点
- Primary objective
研究概览
简要总结
The goal of this clinical trial is to explore the impact of dietary fibre supplement in the form of Vi-Siblin® S (ispaghula seed coats), together with advice on proper healthy diet, on tolerability during dose-escalation of EMP16 in preparation for upcoming Phase III trials. It will also learn about the safety of EMP16. The main questions it aims to answer are:
- How does the combination of EMP16 plus Vi-Siblin® S compare with the combination of conventional orlistat plus placebo dietary fibre supplementation on tolerability during dose-escalation
- What medical problems do participants have when taking EMP16 plus Vi-Siblin® S? Researchers will compare EMP16 combined with Vi-Siblin® S or conventional orlistat combined with placebo (a look-alike substance that contains no Vi-Siblin ® S) dietary fibre supplement.
Participants will:
- Take EMP16 combined with Vi-Siblin® S or conventional orlistat combined with placebo every day for 39 days
- Come to one screening visit and then visit the clinic 6 times for checkups and tests
- Keep an electronic diary to record specific GI tolerability event (GITE) such as oily spotting, faecal incontinence (including flatulence with discharge) and diarrhoea
详细描述
Empros Pharma AB is developing EMP16, a modified release (MR), fixed dose combination (FDC) of orlistat, a gastrointestinal (GI) lipase inhibitor, and acarbose, an intestinal alpha-glucosidase inhibitor, for chronic weight management.
The main purpose of the trial is to explore the impact of dietary fibre supplement in the form of Vi-Siblin® S (ispaghula seed coats), together with advice on proper healthy diet, on tolerability during dose-escalation of EMP16 in preparation for upcoming Phase III trials. Consumption of Vi-Siblin® S together with EMP16 is assumed to reduce prevalence and intensity of GI-related adverse events (AEs), and may also add some extra health benefits, such as further decrease in weight and blood lipids.
This Phase II, randomised, single-blinded trial will be conducted in participants with obesity who have experienced GI side-effects after treatment with EMP16 or conventional orlistat.
Approximately 62 participants are planned to be screened to achieve 39 enrolled participants.
Participants will be randomised 1:2 to EMP16 combined with Vi-Siblin® S (n=13) or conventional orlistat combined with placebo dietary fibre supplement (n=26).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the trial.
- •Have experienced GI tolerability issues (defined as the occurrence of oily spotting, faecal incontinence and/or moderate/severe diarrhoea as reported by the participant) in previous trials using EMP16 or have experienced corresponding GI tolerability issues using conventional orlistat, either in clinical trials or regular clinical treatment of obesity.
- •Males or females aged ≥18 years.
- •At the time of the screening visit, 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 dyslipidaemia (either or not treated with antihyperlipidemic agents). If indicated, plasma/serum total cholesterol, LDL, high-density lipoprotein (HDL), and/or triglycerides (TG) can be measured to verify eligibility as judged by the Investigator.
- •No clinically significant abnormalities regarding physical examination, vital signs, electrocardiogram (ECG), and laboratory values at the time of the screening visit, as judged by the Investigator.
- •Adequate renal function: creatinine <1.5 times the upper limit of normal (ULN).
- •Adequate hepatic function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) <2.5 times ULN and bilirubin <1.5 times ULN.
排除标准
- •Regular use of any obesity medication within 1 month prior to Day 1 at the discretion of the Investigator.
- •Participants who are pregnant, who are currently breastfeeding, who intend to become pregnant within the period of the trial, or who gave birth within the 6 months preceding the screening visit.
- •T2DM treated with medication.
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial including but not limited to:
- •GI problems/diseases, e.g. inflammatory bowel diseases and irritable bowel syndrome (IBS).
- •Cholestasis.
- •Chronical malabsorption syndrome.
- •History of 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.
- •Vitamin B12 deficiency or other signs of achlorhydria. Potential participants with well-treated chronic diseases (e.g., celiac disease and lactose intolerance) may be included in the trial at the discretion of the Investigator.
- •Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- •Any planned major surgery within the duration of the trial.
- •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.
- •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.
- •Untreated high blood pressure (systolic blood pressure >160 mmHg and diastolic blood pressure >100 mmHg at the screening visit).
- •Known hypersensitivity to any of the test substances.
- •Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
- •History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- •Presence or history of drug abuse and/or use of anabolic steroids, as judged by the Investigator.
- •Positive screening result for drugs of abuse or alcohol at the screening visit.
- •Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
- •Plasma donation within 1 month prior to screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
- •Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical trial that included drug treatment within 3 months of the first administration of IMP in this trial. Participants who consented and screened but were not dosed in previous studies are not excluded.
- •The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
研究组 & 干预措施
EMP16 plus Vi-Siblin® S
EMP16: Days 1 to 14: 1 capsule/day, Day 15 to 28, 1 capsule TID and Days 29 to 39: 2 capsules TID. The target dose of EMP16 will be 120 mg orlistat/40 mg acarbose.
Vi-Siblin® S: 20 ml (corresponding to approximately 8 g) in the morning during Days 1 to 14; then 20 ml in the morning and evening the rest of the trial (total daily dose 16 g).
干预措施: EMP16-02 120 mg orlistat/40 mg acarbose (Drug)
EMP16 plus Vi-Siblin® S
EMP16: Days 1 to 14: 1 capsule/day, Day 15 to 28, 1 capsule TID and Days 29 to 39: 2 capsules TID. The target dose of EMP16 will be 120 mg orlistat/40 mg acarbose.
Vi-Siblin® S: 20 ml (corresponding to approximately 8 g) in the morning during Days 1 to 14; then 20 ml in the morning and evening the rest of the trial (total daily dose 16 g).
干预措施: Vi-Siblin® S (Dietary Supplement)
Coventional orlistat plus placebo dietary fibre supplementation
Conventional orlistat: Days 1 to 14: 1 capsule/day, Day 15 to 28, 1 capsule TID and Days 29 to 39: 2 capsules TID). Orlistat in its conventional form will be Alli® 60 mg. The target dose of Alli® will be 120 mg orlistat.
Placebo dietary fibre supplement (Maltodextrin): 20 ml (corresponding to approximately 8 g) in the morning during Days 1 to 14; then 20 ml in the morning and evening the rest of the trial (total daily dose 16 g).
干预措施: Alli® 60 mg (Drug)
Coventional orlistat plus placebo dietary fibre supplementation
Conventional orlistat: Days 1 to 14: 1 capsule/day, Day 15 to 28, 1 capsule TID and Days 29 to 39: 2 capsules TID). Orlistat in its conventional form will be Alli® 60 mg. The target dose of Alli® will be 120 mg orlistat.
Placebo dietary fibre supplement (Maltodextrin): 20 ml (corresponding to approximately 8 g) in the morning during Days 1 to 14; then 20 ml in the morning and evening the rest of the trial (total daily dose 16 g).
干预措施: Maltodextrin (Dietary Supplement)
结局指标
主要结局
Primary objective
时间窗: From start of treatment (day 1) until last visit day 40.
The difference in total GITE score (oily spotting, faecal incontinence \[including flatulence with discharge\] and diarrhoea) between EMP16 combined with Vi-Siblin® S and conventional orlistat combined with placebo dietary fibre supplement
次要结局
- Secondary outcome - GITE(From start of treatment (day 1) until last visit day 40.)
- Secondary outcome - AEs(From start of treatment (day 1) until last visit day 40.)