Double-blind placebo-controlled cross-over MRI study to evaluate the effect of naloxegol and codeine on gastrointestinal motility and volumes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

28 Oct 2024 → 3 Jul 2025

Decision date (initial)

2024-09-16

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: Efficacy

To further understand the mechanism of action of naloxegol in healthy volunteers

Conditions and MedDRA coding

Opioid-induced constipation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained
2. 2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
3. 3. HV is a man or woman aged 18 to 65 years, inclusive, at screening.
4. 4. BMI 18-25
5. 5. Normal stool pattern of between 3 defecations per day and 3 per week with a Bristol Stool Form Scale (BSFS) of 1, 2, 6 or 7 in less than 25% of defaecations.
6. 6. HV has not used any opioid medication 14 days prior to randomization.
7. 7. Medications taken for the treatment of allergies, chronic medical conditions, and migraine headaches can be taken during this study (with the exception of opioids for acute treatment of migraines). HV must be on a stable dose of medication for chronic migraines or preventative therapy for at least 1 month at prescreening. HV on stable doses of antidepressants (i.e., for the 3 months prior to prescreening) will be allowed to participate in the study.

Exclusion criteria 14

1. 1. Participant has a history of diverticulitis, intestinal obstruction, stricture, toxic megacolon, GI perforation, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (eg, aortoiliac disease)
2. 10. Participant has an unstable renal, hepatic, metabolic, or hematologic condition
3. 11. Smoking on the day of the investigation and the day prior to it.
4. 12. Non-removable piercings or metal implants
5. 13. Known allergy towards the study medication
6. 2. Participant has any of the following surgical history: a. Any abdominal surgery within the 3 months prior to prescreening; b. History of major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy more than 3 months earlier are allowed).
7. 3. Participant has asthma
8. 4. Participant has a history of a cardiovascular event, including stroke, myocardial infarction, congestive heart failure, or transient ischemic attack within 6 months prior to prescreening
9. 5. Any other disorder, which in the Investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol
10. 6. Any prior or concomitant treatment(s) that might jeopardise the participant’s safety or that would compromise the integrity of the Trial a. current evidence of laxative abuse or history of drug abuse. b. current (within 14 days of randomization) or expected use of any narcotic or opioid containing agents, docusate, enemas, GI preparations (including antacids containing aluminum or magnesium, antidiarrheal agents, antinausea agents, antispasmodic agents, bismuth, or prokinetic agents) (see 5.3 prohibided concomitant medication). c. Intake of drugs that interfere with the GI motility and fluid balance for 1 month prior to the investigation (see 5.3 prohibided concomitant medication). d. Consumption of grapefruit (juice) or medication that interferes with Naloxegol (CYP3A4 inducers/blockers).
11. 7. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
12. 8. Participation in an interventional Trial with an investigational medicinal product (IMP) or device within 30 days prior to randomisation, or is currently enrolled in an investigational study
13. 9. HV has a history of malignancy within 5 years before prescreening (except squamous and basal cell carcinomas and cervical carcinoma in situ).
14. 14. Subjects known to be ultrarapid metabolizers of CYP2D6

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. investigation of the effect of the 3 drug-arms (placebo+placebo, naloxegol+codeine, placebo+codeine) on both colonic motility and segmental colorectal volumes at baseline, after an oat porridge meal and after bisacodyl administration

Investigational products

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

Test 2

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Jan Tack

Public contact point

Organisation

UZ Leuven

Contact name

Jan Tack

Locations

1 EU/EEA country · 1 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

Documents 1 file

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