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

NCT04966559 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: PAMORA_RAP2021-000069-34N-20210034
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 5

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.

Conditions

Pancreatitis, Acute

Outcome Measures

Primary Outcomes (1)

• Number of AP attacks verified by the Atlanta Criteria

  The primary outcome is defined as time to (recurrent) AP attack(s) verified by the Atlanta Criteria between the naldemedine group and the placebo group. The Atlanta Criteria is the current gold standard for the diagnosis of AP attack, and it requires a minimum of two out three of the following features: (i) Abdominal pain typical for acute pancreatitis featuring acute onset of a severe and persistent epigastric pain radiating to the back (ii) Serum amylase levels \> three times greater than the normal upper limit (iii) Findings of pancreatic inflammation in contrast-enhanced computed tomography, magnetic resonance imaging or transabdominal ultrasonography.

  Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months

Secondary Outcomes (9)

• Pain intensity

  Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months

• Gut function (BSFS)

  Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months

• Gut function (GSRS)

  Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months

• Health resource utilization

  Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months

• Pancreatic volume

  Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months

Study Arms (2)

Placebo treatment

PLACEBO COMPARATOR

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

Drug: Placebo treatment

Naldemedine treatment

ACTIVE COMPARATOR

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

Drug: Naldemedine 0.2 MG Oral Tablet

Interventions

Placebo treatment DRUG

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

Placebo treatment

Naldemedine 0.2 MG Oral Tablet DRUG

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

Naldemedine treatment

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• Asbjørn Mohr Drewes: lead
• Odense University Hospital: collaborator
• Hvidovre University Hospital: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator
• Karolinska University Hospital: collaborator

Study Sites (5)

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

Aalborg, Jutland, 9000, Denmark

Location

Digestive Disease Center K, Bispebjerg University Hospital

Bispebjerg, Denmark

Location

Gastrounit, Hvidovre University Hospital

Hvidovre, Denmark

Location

Odense Pancreas Center

Svendborg, Denmark

Location

Karolinska University Hospital

Stockholm, Solna (l1:00), SE-171 76, Sweden

Location

Related Publications (2)

• Cook ME, Knoph CS, Davidsen L, Frokjaer JB, Bruun NH, Novovic S, Hadi A, Jorgensen MT, Mortensen MB, Schaffalitzky O, Nielsen LBJ, Berner-Hansen M, Drewes AM, Olesen SS. Naldemedine for the Prevention of Recurrent Acute Pancreatitis: A Randomised, Double-Blind, Placebo-Controlled Trial. United European Gastroenterol J. 2026 Feb;14(1):e70178. doi: 10.1002/ueg2.70178.

  PMID: 41553774 DERIVED

• 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.

  PMID: 37127657 DERIVED

MeSH Terms

Conditions

Pancreatitis

Interventions

naldemedine; Tablets

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Asbjørn M. Drewes, Professor

  Aalborg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chief Physician, MD, PhD, DMSc

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: January 12, 2022
• Primary Completion: March 30, 2024
• Study Completion: June 1, 2024
• Last Updated: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

DK (4); SE (1)