Effects of a Peripherally Acting µ-opioid Receptor Antagonist on Recurrent Acute Pancreatitis

NCT ID: NCT04966559

Last Updated: 2024-03-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-12
• Study Completion Date: 2024-06-01

Brief Summary

This study will investigate the effect of a peripheral acting opioid antagonist (PAMORA) on the disease course of patients with recurrent acute inflammation of the pancreas (acute pancreatitis). The study will be conducted by treating outpatients suffering from recurrent acute pancreatitis with a PAMORA (naldemedine) for 12 months.

Detailed Description

In this study, the effects of a peripheral acting µ-opioid receptor antagonist (PAMORA) on disease recurrence and progression in patients with recurrent acute pancreatitis (RAP) will be investigated. Patients with RAP will be administered 0,2 mg naldemedine orally daily or matching placebo. This medication is defined as the investigational product. Naldemedine is approved by the European Medical Agency for treatment of opioid-induced constipation. This PAMORA have not previously been investigated in patients with pancreatitis. The dose regimes for this study will be according to label. It has previously been shown, in patients with opioid-induced obstipation and healthy subjects, that opioid antagonism incl. PAMORA treatment increases gut motility, relaxes gastrointestinal sphincters, increases the intestinal water content and improves the immune response, without affecting analgesia. The affinity of PAMORAs to the µ-opioid receptors is much stronger than opioid analgesics. Therefore, they as antagonists have the potential to counteract the harmful effects of opioids on the gut mucosa, bacterial translocation and inflammation despite the high levels of exogenous opioids present in patients with pancreatitis. PAMORAs do not cross the blood-brain barrier and consequently do not interfere with analgesia or other central effects of opioids.

It is hypothesized that treatment with the PAMORA naldemedine will antagonize the harmful effects of opioids without reducing analgesia in patients with RAP and hence reduce disease severity and improve clinical outcomes. If successful, this study will for the first time document the effects of a targeted pharmacotherapy in RAP with the potential benefit of improved patient outcomes.

Conditions

Pancreatitis, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo treatment

Film-coated matched placebo-tablets consisting of:

Core:

Mannitol, USP/Ph. Eur./JP Croscarmellose Sodium, NF/Ph. Eur./JP Magnesium Stearate, NF/Ph. Eur./JP

Coating:

Opadry Yellow Purified Water, USP/EP

Group Type: PLACEBO_COMPARATOR

Placebo treatment

Intervention Type: DRUG

Active drug/placebo is handed out equivalent of 1 tablet of 0,2 mg Naldemedine or placebo daily for 365 days.

Naldemedine treatment

Film-coated matched active-tablets consisting of:

Core:

Naldemedine Tosylate (0,2 mg) Mannitol, USP/Ph. Eur./JP Croscarmellose Sodium, NF/Ph. Eur./JP Magnesium Stearate, NF/Ph. Eur./JP

Coating:

Opadry Yellow Purified Water, USP/EP

Group Type: ACTIVE_COMPARATOR

Naldemedine 0.2 MG Oral Tablet

Intervention Type: DRUG

Active drug/placebo is handed out equivalent of 1 tablet of 0,2 mg Naldemedine or placebo daily for 365 days.

Interventions

Placebo treatment

Active drug/placebo is handed out equivalent of 1 tablet of 0,2 mg Naldemedine or placebo daily for 365 days.

Intervention Type: DRUG

Naldemedine 0.2 MG Oral Tablet

Active drug/placebo is handed out equivalent of 1 tablet of 0,2 mg Naldemedine or placebo daily for 365 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent before any study specific procedures
• Able to read and understand Danish or Swedish (depending on site)
• Male or female age between 18 and 74 years
• At least one attack of non-biliary AP (as defined by the revised Atlanta criteria) within the last 12 months and at least two attacks within 5 years
• Clinically stable at time of inclusion
• The researcher believes that the participant understands what the study entails, is capable of following instructions, can attend when needed, and is expected to complete the study
• The investigator will ensure that fertile female participants have a negative pregnancy test before treatment initiation and use contraception during the study period. The following methods of contraception, if properly used, are generally considered reliable: oral contraceptives, patch contraceptives, injection contraceptives, vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation), vasectomized partner, double barrier (condom and pessary), or sexual abstinence. Methods of contraception will be documented in the source documents

Exclusion Criteria

• Known allergy towards study medication
• Known or suspected major stenosis or perforation of the intestines
• Known or suspected abdominal cancer (incl. intestine, pancreas and the biliary tree)
• Pre-existing renal insufficiency (defined as habitual eGFR below 45)
• Female participants that are lactating
• Severe pre-existing comorbidities (assessed by investigator upon inclusion)
• Attack of AP requiring admission within two weeks prior to inclusion
• Gallstone etiology of RAP (MRCP or endoscopic ultrasound excluding biliary etiology of AP must be available prior to enrolment as part of the protocol)
• Treatment with potent CYP3A4-inhibitors (ketoconazol, itraconzol, ritonavir) or P-gp inhibitors (e.g. cyclosporine).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

Hvidovre University Hospital

OTHER

Sponsor Role: collaborator

University Hospital Bispebjerg and Frederiksberg

OTHER

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

Asbjørn Mohr Drewes

OTHER

Sponsor Role: lead

Responsible Party

Asbjørn Mohr Drewes

Professor, Chief Physician, MD, PhD, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Asbjørn M. Drewes, Professor

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital

Locations

Mech-Sense, Department of Medical Gastroenterology, Aalborg University Hospital

Aalborg, Jutland, Denmark

Digestive Disease Center K, Bispebjerg University Hospital

Bispebjerg, , Denmark

Gastrounit, Hvidovre University Hospital

Hvidovre, , Denmark

Odense Pancreas Center

Svendborg, , Denmark

Karolinska University Hospital

Stockholm, Solna (l1:00), Sweden

Countries

Denmark; Sweden

References

Cook ME, Knoph CS, Fjelsted CA, Frokjaer JB, Bilgrau AE, Novovic S, Jorgensen MT, Mortensen MB, Nielsen LBJ, Hadi A, Berner-Hansen M, Rutkowski W, Vujasinovic M, Lohr M, Drewes AM, Olesen SS. Effects of a peripherally acting micro-opioid receptor antagonist for the prevention of recurrent acute pancreatitis: study protocol for an investigator-initiated, randomized, placebo-controlled, double-blind clinical trial (PAMORA-RAP trial). Trials. 2023 May 1;24(1):301. doi: 10.1186/s13063-023-07287-z.

Reference Type: DERIVED

PMID: 37127657 (View on PubMed)

Other Identifiers

2021-000069-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N-20210034

Identifier Type: OTHER

Identifier Source: secondary_id

PAMORA_RAP

Identifier Type: -

Identifier Source: org_study_id