Study Exploring the Supportive Effect of Acarbose in Weight Management

A 26-week, Double-blind, Randomized Study in Participants With Overweight or Obesity Investigating the Added Contribution of Acarbose in EMP16 on Efficacy, Safety and Tolerability

This is a randomized, double-blind study in participants with overweight or obesity in which the effect of acarbose and the impact of dose on efficacy, safety and tolerability is investigated by comparing the EMP16 combination product with modified release (MR) orlistat, orlistat in its conventional dosage form and placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Overweight or Obesity
• Intervention / Treatment: Drug: EMP16-120/40; Drug: MR orlistat 120 mg; Drug: Conventional orlistat 120 mg,; Drug: Placebo; Drug: EMP16-60/20

Detailed Description

The study will be conducted at 3 research sites in Sweden. A total of 320 randomized patients are expected to participate in the study for approximately 31 weeks, including a screening period of up to 5 weeks and a 26-weeks treatment period.

EMP16 is indicated for people with obesity with an initial BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of other risk factors (e.g., hypertension, glucose dysregulation and T2DM, and/or dyslipidemia).

Participants will be randomized to either of 5 arms:

• EMP16-120/40, 80 participants
• MR orlistat 120 mg, 80 participants
• Conventional orlistat 120 mg, 80 participants
• EMP16-60/20, 40 participants
• Placebo, 40 participants

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Linköping, Sweden, SE-582 13
    • CTC Ebbepark
  • Solna, Sweden, SE-171 64
    • CTC Karolinska
  • Uppsala,, Sweden, SE-752 37
    • Clinical Trial Consultants (CTC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion 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), Type 2 Ddabetes 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: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase <2.5 times upper level of normal (ULN) and bilirubin <1.5 times ULN.

Exclusion Criteria:

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. Type 2 diabetes 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EMP16-120/40; EMP16 120 mg orlistat/40 mg acarbose (referred to as EMP16-120/40), 80 participants.	Drug: EMP16-120/40; EMP16 is supplied as oral MR capsules with the strength of 60 mg orlistat/20 mg acarbose. Dosage: week 1-2: 60 mg orlistat/20 mg acarbose (1 capsule per day), week 3-4: 60 mg orlistat/20 mg acarbose (1 capsule TID), week 5-26: 60 mg orlistat/20 mg acarbose (2 capsules TID).
Active Comparator: MR orlistat; MR orlistat 120 mg, 80 participants.	Drug: MR orlistat 120 mg; MR orlistat 120 mg is the same as EMP16-120/40 but without the acarbose component in matching oral capsules. Dosage:. week 1-2: 60 mg MR orlistat (1 capsule per day), week 3-4: 60 mg MR orlistat (1 capsule TID), week 5-26: 60 mg MR orlistat (2 capsules TID).
Active Comparator: Conventional orlistat; Conventional orlistat 120 mg, 80 participants.	Drug: Conventional orlistat 120 mg,; Orlistat in its conventional form will be Alli® 60 mg during week 1 to 4 and Xenical® 120 mg from week 5 and onwards in matching oral capsules. Dosage: week 1-2: 60 mg conventional orlistat (1 capsule per day), week 3-4: 60 mg conventional orlistat (1 capsule TID), week 5-26: 120 mg conventional orlistat plus placebo (1 capsule of each TID).; Other Names: Xenical; Drug: Placebo; Dosage: week 1-2: Placebo (1 capsule per day), week 3-4: Placebo (1 capsule TID), week 5-26: Placebo (2 capsules TID)
Experimental: EMP16-60/20; EMP16 60 mg orlistat/20 mg acarbose (referred to as EMP16-60/20), 40 participants.	Drug: Placebo; Dosage: week 1-2: Placebo (1 capsule per day), week 3-4: Placebo (1 capsule TID), week 5-26: Placebo (2 capsules TID); Drug: EMP16-60/20; Dosage: week 1-2: 60 mg orlistat/20 mg acarbose (1 capsule per day), week 3-4: 60 mg orlistat/20 mg acarbose (1 capsule TID), week 5-26: 60 mg orlistat/20 mg acarbose plus placebo (1 capsule of each TID)
Placebo Comparator: Placebo; Placebo, 40 participants	Drug: Placebo; Dosage: week 1-2: Placebo (1 capsule per day), week 3-4: Placebo (1 capsule TID), week 5-26: Placebo (2 capsules TID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative (%) change from baseline in body weight at week 26	Efficacy endpoints	Baseline and week 26
Proportion of participants with ≥5% decrease in body weight at week 26 [Please note: This is an FDA required outcome, cannot use "change"]	Efficacy endpoints	Baseline and week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative (%) change from baseline in body weight at week 26 (secondary and exploratory comparisons)	Efficacy endpoints	Baseline and week 26
Proportion of participants with ≥5% (secondary and exploratory comparisons) and ≥10% (all comparisons) decrease in body weight at week 18 and week 26	Efficacy endpoints	Baseline, week 18 and 26
Absolute change from baseline in body weight at week 26	Efficacy endpoints	Baseline and week 26
Relative (%) change from baseline in body weight during the 26-weeks treatment period	Efficacy endpoints	Baseline to week 26
Absolute change from baseline in body weight during the 26-weeks treatment period	Efficacy endpoints	Baseline to week 26
Absolute change from baseline in body mass index (BMI) measured as weight (kg) divided by height (m) squared	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in waist circumference	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in sagittal diameter	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in percentage body fat	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in Quality of life as measured by the questionnaire Rand-36 (9 different domains)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in Quality of life as measured by the questionnaire EQ-5D-5L (measured as one summative value)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in self reported meal pattern. Short questionnaire where points are depending on adherence to the Nordic Nutrition recommendations	Efficacy endpoints.	Baseline and week 26
Absolute change from baseline in self reported sleep, where higher points are given for good sleep duration and good sleep quality	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in self reported physical activity, where higher points are given for longer duration of moderate and intense physical activity	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting hemoglobin A1c (HbA1c)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting glucose	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting insulin	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting total cholesterol	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting high-density lipoprotein (HDL)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting low-density lipoprotein (LDL)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting triglycerides (TGs)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting Apolipoprotein A1 (ApoA1)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting Apolipoprotein B (ApoB)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting high sensitivity C-reacting protein (hs-CRP)	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in fasting albumin	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in homeostatic model assessment (HOMA) index	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in Visceral adiposity index (VAI)	Efficacy endpoints VAI Males = (WC/(39.38+(1.88*BMI)))*(TG/1.03)*(1.31/HDL) VAI Females = (WC/(36.58+(1.89*BMI)))*(TG/0.81)*(1.52/HDL)	Baseline and week 26
Absolute change from baseline in Fatty liver index (FLI)	Efficacy endpoints. Measured as FLI = 100*e to the power of y /(1+e to the power of y) y= 0.953*ln(TG)+0,139*BMI+0.718*ln(GGT)+0.053*WC-15.3745	Baseline and week 26
Absolute change from baseline in systolic and diastolic blood pressure	Efficacy endpoints	Baseline and week 26
Absolute change from baseline in heart rate	Efficacy endpoints	Baseline and week 26
Tolerability, assessed by conventional adverse event (AE) reporting (with special focus on oily spotting and fecal incontinence)	Safety & tolerability endpoints	IMP administration until the end-of-study visit. Assessed at all nine visits (both outpatient and telephone visits)
Number of withdrawals from study (total and gastrointestinal [GI] related)	Safety & tolerability endpoints	Visit 1 until the end-of-study visit. Assessed at all nine visits (both outpatient and telephone visits)
Absolute change from baseline in fasting liver enzymes	Safety & tolerability endpoints (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transferase)	Baseline and week 26

Collaborators and Investigators

• Sponsor: Empros Pharma AB
• Collaborators: CTC Clinical Trial Consultants AB

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Actual): November 21, 2023
• Study Completion (Estimated): March 15, 2024

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Overweight, Obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Anti-Obesity Agents; Orlistat
• Other Study ID Numbers: EP-003; 2022-003320-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No