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临床试验/NCT04521751
NCT04521751已完成1 期

Lean Efficacy Phase IIa Proof of Concept Trial (LEAAP). A Study in Overweight and Obese Patients During Twenty-six Weeks, Investigating the Effect of EMP16-02 on Body Weight, Safety and Clinical Biomarkers

Empros Pharma AB1 个研究点 分布在 1 个国家目标入组 156 人开始时间: 2020年5月7日最近更新:
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适应症
干预措施
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试验速览

阶段
1 期
状态
已完成
入组人数
156
试验地点
1
主要终点
Body weight, relative (%) change from baseline for EMP16-02 (120 mg O/40 mg A)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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:

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
Triple (Participant, Investigator, Outcomes Assessor)

盲法说明

This is a double-blind study and the allocation of treatments will not be disclosed until clean file has been declared and the database has been locked.

Active treatment and placebo capsules are identical in appearance.

入排标准

年龄范围
18 Years 至 75 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Willing and able to give written informed consent for participation in the study.
  • •Aged ≥ 18 and ≤ 75 years.
  • •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 or HbA1c 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.
  • •Acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
  • •Adequate renal and hepatic function as judged by the Investigator in accordance with the expected disease profile
  • •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).
  • •Willing to eat three meals per day, and willing to eat breakfast during the visits to the clinic.
  • •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).

排除标准

  • •T2DM treated with medication.
  • •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.
  • •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.
  • •Any planned major surgery within the duration of the study.
  • •Untreated high blood pressure (above 160/100 mmHg at screening).
  • •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.
  • •Known hypersensitivity to any of the test substances. History of hypersensitivity to drugs with a similar chemical structure or class to orlistat and acarbose.
  • •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.
  • •Cholestasis.
  • •Previous gastrointestinal surgery that might influence gastrointestinal function significantly, previous bariatric surgery, and previous gallbladder surgery as judged by the investigator.
  • •Known vitamin B12 deficiency or other signs of achlorhydria.
  • •Chronical malabsorption syndrome.
  • •Clinically significant abnormal laboratory values at screening as judged by the investigator.
  • •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.
  • •A personal or family history of Medullary Thyroid Carcinoma (MTC).
  • •A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  • •Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse, as judged by the Investigator.
  • •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.
  • •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV.
  • •Plasma donation within one month of screening or any blood donation (or corresponding blood loss) during the three months prior to screening.
  • •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.
  • •Investigator considers the patient unlikely to comply with study procedures, restrictions and requirements.
  • •Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
  • •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.
  • •Patients with swallowing disorders, which may affect the patient's capability to swallow the IMP.

研究组 & 干预措施

EMP16-02 120 mg orlistat/40 mg acarbose

Experimental

Dosage form: Oral, modified-release (MR) fixed dose combination (FDC) of orlistat and acarbose formulated in capsules.

Dosage: 120 mg O/40 mg A (given as 2 capsules EMP16-02-60/20). Frequency: Three times daily (TID) together with the three main daily meals .Taken halfway through each meal, together with approximately 100-200 mL water (or other drink).

Duration: 26 weeks.

干预措施: EMP16-02 120 mg orlistat/40 mg acarbose (Drug)

EMP16-02 150 mg orlistat/50 mg acarbose

Experimental

Dosage form: Oral, modified-release (MR) fixed dose combination (FDC) of orlistat and acarbose formulated in capsules.

Dosage: 150 mg O/50 mg A (given as 1 capsule EMP16-02-90/30 and 1 capsule EMP16-02-60/20).

Frequency: Three times daily (TID) together with the three main daily meals .Taken halfway through each meal, together with approximately 100-200 mL water (or other drink).

Duration: 26 weeks.

干预措施: EMP16-02 150 mg orlistat/50 mg acarbose (Drug)

Placebo

Placebo Comparator

Dosage form: Matching, oral capsule. Identical in appearance but contain only cellulose.

Dosage: Placebo (given as 2 placebo capsules) Frequency: Three times daily (TID) together with the three main daily meals .Taken halfway through each meal, together with approximately 100-200 mL water (or other drink).

Duration: 26 weeks.

干预措施: Placebo (Drug)

结局指标

主要结局

Body weight, relative (%) change from baseline for EMP16-02 (120 mg O/40 mg A)

时间窗: From first dose to last dose (week 26). Measured at baseline and week 26.

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.

次要结局

  • Body weight, absolute change from baseline for EMP16-02 (120 mg O/40 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Waist circumference, absolute change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • BMI, relative (%) and absolute change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Questionnaire Satiety and craving, after 14 and 26 weeks for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Albumin: Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Body weight, relative (%) and absolute change from baseline for EMP16-02 (150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Sagittal diameter, absolute change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Percentage body fat, relative (%) and absolute change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Proportion of patients with ≥5% and ≥10% decrease in body weight for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Haemoglobin A1C (HbA1c): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Glucose: Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Insulin: Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Total cholesterol: Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • High-density lipoprotein (HDL): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Low-density lipoprotein (LDL): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Triglycerides: Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • High-sensitivity C-reactive protein (hs CRP): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Alanine aminotransferase (ALT): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Aspartate aminotransferase (AST): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Alkaline phosphatase (ALP): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Gamma-glutamyl transferase (GGT): Relative (%) and absolute change from baseline for EMP16 02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)
  • Proportion of diabetic (fasting glucose ≥ 7.0 mmol/L) and prediabetic patients (fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L) for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Blood pressure, relative (%) and absolute change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 14 and week 26.)
  • Health and life quality questionnaire (RAND-36), change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Activity and sleep questionnaire, change from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14 and week 26.)
  • Drop-out rate (overall and GI-related), for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose until the date of drop-out, assessed up to 26 weeks.)
  • Frequency and severity of AEs, for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose until date of resolution of last AE registered or to End of study visit (week 28), whichever comes first.)
  • Bilirubin (total), clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Bilirubin (conjugated), clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Calcium, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Creatinine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Phosphate, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Potassium, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Sodium, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Urea, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Haematocrit, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Haemoglobin (Hb), clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Platelet count, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Red blood cell (RBC) count, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • White blood cell (WBC) count, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Activated Partial Thromboplastin Time (APTT), clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Prothrombin Complex International Normalised Ratio (PK[INR]), clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Erythrocytes in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Glucose in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Ketones in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Leucocytes in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Nitrites in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • pH in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Protein in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Specific gravity in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Urobilinogen in urine, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • ECG HR interval, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • ECG PR interval, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • ECG QRS interval, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • ECG QT interval, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • ECG QTcF interval, clinically significant relative (%) and absolute changes from baseline for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline and week 26.)
  • Gastrointestinal symptom rating scale (GSRS), for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, after 2, 4, 6, 8, 14 and 26 weeks.)
  • IMP compliance, for EMP16-02 (120 mg O/40 mg A and 150 mg O/50 mg A)(From first dose to last dose (week 26). Measured at baseline, week 7, week 14, and week 26.)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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