Control Of BioEquivalence with Xenical (COBEX): A Phase I, randomized, active-control study to evaluate EMP22 pharmacodynamics and EMP16 pharmacokinetics versus Xenical® in healthy volunteers.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Empros Pharma AB

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

22 Sep 2023 → 22 Nov 2023

Decision date (initial)

2023-09-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Bioequivalence, Pharmacodynamic

To confirm the PD equivalence of the MR orlistat component of EMP16 (i.e., EMP22) and Xenical® (Part I).

This Phase I, active-controlled, randomised trial will be conducted in 2 parts. Part I aims to confirm the PD equivalence of EMP22 and Xenical® based on percent faecal fat excretion at steady state. EMP22 (also referred to as MR orlistat) has the same MR properties as EMP16 but lacks the acarbose component. Part II will explore the PK properties of EMP16 alone and vs. Xenical®. Part I will be conducted in a single-blind, cross-over fashion while Part II will have an open-label, fixed-sequence design.

Secondary objectives 2

1. To explore the PK properties of EMP16 (PartII).
2. To compare the bioavailability of orlistat in EMP16 and Xenical® (Part II).

Conditions and MedDRA coding

Obesity

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Willing and able to give written informed consent for participation in the trial.
2. Healthy male or female aged 20 to 55 years inclusive.
3. Participants with a BMI between 20 and 27 kg/m² or participants with a BMI >27 kg/m2 and normal body fat composition (10 to 25% for men and 20 to 30% for women measured using a bioimpedance scale) at screening.
4. Weight stable (<5% self-reported change during the previous 3 months preceding screening).
5. Participants with a self-perceived normality in defecation habits, normally with a stool frequency of at least once daily.
6. Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, electrocardiogram (ECG) and laboratory values at the time of the screening visit, as judged by the Investigator.

Exclusion criteria 18

1. 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. • 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. • Chronical malabsorption syndrome. • History of severe allergic, cardiac or hepatic disease.
2. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
3. Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
4. Any planned major surgery within the duration of the trial.
5. Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
6. Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
7. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the screening visit, as judged by the Investigator.
8. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class as orlistat or acarbose.
9. Regular use of any prescribed or non-prescribed medications (including, but not limited to, antacids, analgesics, herbal remedies, vitamins and minerals) within 2 weeks prior to the first administration of IMP except as outlined in Section 9.6.2.3. in the Protocol.
10. 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. Subjects consented and screened but not dosed in previous studies are not excluded.
11. Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week is allowed before the screening visit.
12. Positive screening result for drugs of abuse or alcohol at the screening visit.
13. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
14. Presence or history of drug abuse, as judged by the Investigator.
15. History of, or current use of anabolic steroids, as judged by the Investigator.
16. Excessive caffeine consumption defined by a daily intake of > 5 cups (1 cup = approximately 240 mL) of caffeine containing beverages, as judged by the Investigator.
17. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
18. The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percent of faecal fat excretion expressed as a ratio of the amount of fat excretion over a 24-hour period at steady-state relative to the amount of daily ingested fat.

Secondary endpoints 2

1. Maximum plasma concentration (Cmax), Time to Cmax (Tmax) and area under the plasma concentration vs. time curve from time 0 to time t AUC0-t for orlistat and acarbose
2. Cmax, Tmax and AUC0-t for orlistat

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Empros Pharma AB

Sponsor organisation

Empros Pharma AB

Address

Nanna Svartz Vag 4

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Empros Pharma AB

Contact name

Ulf Holmbäck

Public contact point

Organisation

Empros Pharma AB

Contact name

Ulf Holmbäck

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications