A Double-Blinded, Placebo-Controlled Exploratory Study to Investigate the Efficacy and Safety of Flexible dosing of Oral Lidocaine (ORE-001) to Reduce Abdominal Discomfort and Prevent Early Satiety in Anorexia Nervosa Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Orexa B.V.

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

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

Decision date (initial)

2025-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Orexa BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the efficacy of oral ORE-001 in reducing satiety and postprandial fullness in anorexia nervosa patients

Secondary objectives 8

1. To evaluate the efficacy of oral ORE-001 in reducing late fullness
2. To evaluate the efficacy of oral ORE-001 in reducing GI symptoms after the consumption of a meal
3. To evaluate the efficacy of oral ORE-001 in increasing weight gain
4. To evaluate the efficacy of oral ORE-001 in increasing the amount of food eaten.
5. To evaluate the impact of ORE-001 on Quality of Life in anorexia nervosa patients
6. To evaluate the impact of ORE-001 on sleep quality in anorexia nervosa
7. To evaluate the safety and tolerability of oral ORE-001 in patients with anorexia nervosa
8. To explore the pathophysiological mechanisms involved in anorexia nervosa

Conditions and MedDRA coding

Anorexia nervosa

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients must be able to understand the requirements of the study and give written informed consent prior to study start.
2. Female between 18 and 45 years of age (both inclusive).
3. Patients requiring hospitalization and under psychological treatment for anorexia nervosa for at least 3 months.
4. Patient is highly likely to comply with the protocol and complete the study.
5. BMI at baseline ˃13 (moderate-to-severe AN according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
6. Classified as restricting and binge-eating/purging types of AN according to DSM-5.
7. Diagnosis of anorexia nervosa according to DSM-5 criteria.

Exclusion criteria 12

1. Any contraindication as per summary of product characteristic for the usage of lidocaine.
2. Any other condition, including but not limited to epilepsy, myasthenia gravis, cardiac conduction disturbances, congestive heart failure, bradycardia, severe shock, impaired respiratory function or impaired renal function with creatinine clearance (CrCl) less than 10 ml/min, which in the opinion of the investigator precludes the patient’s participation in the study.
3. Patients with close affiliation with the Investigator or persons working at the respective study sites or patients who are an employee of the sponsor.
4. History of uncontrolled (at the discretion of the investigator) cardiovascular, renal, hepatic and/or liver failure.
5. History of severe allergic or anaphylactic reactions, especially to local anesthetics.
6. Clinically significant (at the discretion of the investigator) abnormal ECG.
7. Intake of any class 1B antiarrhythmic drugs if used for antiarrhythmic purpose (e.g., lidocaine, mexiletine, phenytoin) and of any class 3 antiarrhythmic drugs - potassium channel blockers (e.g., amiodarone, dronedarone, sotalol, ibutilide, dofetilide, bretylium).
8. Intake of concomitant medication that has an impact on stomach pH like proton pump inhibitors. These compounds may have an impact on the bioavailability of the ORE-001.
9. Significant (at the discretion of the investigator) symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection (especially with need of antibiotic treatment) within the past 2 weeks prior to study medication administration.
10. Experimental agent within 30 days or ten half-lives, whichever is longer, prior to study medication administration.
11. Pregnancy, lactation, or planning to become pregnant during the study. Females of childbearing potential must have a negative pregnancy test prior to starting treatment and practice highly effective methods of birth control throughout the study period (unless postmenopausal or surgically sterile, or whose sole sexual partner had a successful vasectomy). Highly effective contraceptives measures according to CTCG recommendation, version 1.2, 07 March 2024, are: a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral/intravaginal/transdermal or progestogen-only hormonal contraception associated with inhibition of ovulation: oral/ injectable/ implantable for at least 3 months prior to dosing and continuing through the study completion. b. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) for at least 3 months prior to dosing and continuing through the study completion. c. Bilateral tubal occlusion. d. Vasectomized partner. e. Sexual abstinence. Note: Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms) or have FSH level of at least 40 U/ml at screening (to confirm menopause) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
12. Hypersensitivity to the IMP or to any excipients used in the formulation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference between ORE-001 and placebo in change from baseline in VAS scores for satiety sensations on Day 28

Secondary endpoints 8

1. Difference between ORE-001 and placebo in change from baseline in late fullness (prior to lunch) in VAS scores for satiety sensations on Day 28
2. Difference between ORE-001 and placebo in change from baseline in VAS score for GI symptoms on Day 28
3. Difference between ORE-001 and placebo in change from baseline in body weight at Day 28.
4. Daily change from baseline in the weight of food and calorie intake per meal.
5. Difference between ORE-001 and placebo in change from baseline in total IEDOQL score on Day 28.
6. Difference between ORE-001 and placebo in change from baseline in MOS sleep scale on Day 28.
7. Treatment-Emergent Adverse Events (AE) and serious adverse events (SAE) up to end of study
8. Change from Baseline in the levels of biomarkers (Leptin, ghrelin, oxytocin, peptide Y (PYY), and brain-derived neurotropic factor (BDNF)) associated with satiety at End of Treatment

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Orexa B.V.

Sponsor organisation

Orexa B.V.

Address

Berghemseweg 8

City

Herpen

Postcode

5373 KH

Country

Netherlands

Scientific contact point

Organisation

Orexa B.V.

Contact name

Bernardus Peeters

Public contact point

Organisation

Orexa B.V.

Contact name

Bernardus Peeters

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 13 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