PP100-01 (calmangafodipir) for Overdose of Paracetamol (The POP Trial)
Research type
Research Study
Full title
A Randomised Open Label Exploratory, Safety and Tolerability Study with PP100-01 in Patients Treated with the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose
IRAS ID
220617
Contact name
James W Dear
Contact email
Sponsor organisation
PledPharma AB
Eudract number
2017-000246-21
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Paracetamol is the most common drug taken in overdose by patients in the UK and most common cause of acute liver failure. Fortunately, its toxic effect on the liver is potentially preventable by quick treatment with the antidote acetylcysteine (known as NAC). Some patients still develop liver injury despite treatment with NAC.
This project will test a 12hr NAC treatment (standard care at the Royal Infirmary of Edinburgh) and a new treatment, which gives NAC together with a ‘superoxide dismutase (SOD) mimetic’, PP100-01. PP100-01 is effective at blocking the stress on organs caused by medications. It has been given to patients with cancer without safety concerns (PP100-01 prevented nerve damage due to cancer therapy in this group). However, this group have symptoms relating to their diagnosis and chemotherapy that could hide PP100-01-related side effect. Furthermore, in the future we plan to use PP100-01 in combination with NAC. Therefore, before going on to do a larger study to see if PP100-01 prevents liver damage, we wish to gain confidence that the combination of PP100-01 and NAC is tolerated well by patients. The patient group to be included are adults who have taken an overdose of paracetamol (either deliberately or by mistake) who require NAC treatment. The study will include 3 treatment groups, each group having a higher dose of PP100-1 than the last. A Safety Data Monitoring Committee will analyse the safety data and side effects after each treatment group and a decision will be made whether or not to continue to the next dose escalation. All further patient enrolment will be paused pending advise from the SDMC if one of the following stopping rules have been met: 1. Patient death, admission to a Critical Care Unit or admission to a Liver Transplantation Unit due to any reason, or 2. One SUSAR that definitely or probably relates to either PP100-01 or NAC or both. Each group will comprise 8 patients (6 NAC and PP100-01 together, 2 NAC alone) and 24 patients will be enrolled in total.
The main aim of this study is to check that the combination of NAC and PP100-01 does not produce any unexpected symptoms. Furthermore, the study is designed to provide evidence about paracetamol toxicity, including the body’s response to liver injury, together with data on the blood concentrations of PP100-01 resulting from the treatment used.
REC name
West of Scotland REC 1
REC reference
17/WS/0047
Date of REC Opinion
11 Apr 2017
REC opinion
Further Information Favourable Opinion