The objective of this study is to develop a therapeutic regimen for paracetamol/acetaminophen overdose (POD) where a novel NAC 12hr regime is combined with a superoxide dismutase (SOD) mimetic, PP100-01 in order to evaluate if reduction of the oxidative stress on the liver will be safe and well tolerated. MedDRA version: 20.0 Level: PT Classification code 10033295 Term: Overdose System Organ Class: 10022117 - Injur
Conditions
Interventions
Product Name: Calmangafodipir
Product Code: PP100-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NA
Sponsors
PledPharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Any patient with capacity admitted to hospital within 24 hrs of either a single acute POD or more than one dose of paracetamol (staggered overdose) and deemed to require treatment with NAC. 2. Provision of written informed consent 3. Males and females of at least 16 years of age Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients that do not have the capacity to consent to participate in the study 2. Patients detained under the Mental Health Act or deemed unfit by the Investigator to participate due to mental health. 3. Patients with known permanent cognitive impairment 4. Patients who are pregnant or nursing 5. Patients who have previously participated in the study 6. Unreliable history of paracetamol overdose 7. Patients presenting after 24hrs of overdose 8. Patients who take anticoagulants (e.g. warfarin) therapeutically or have taken an overdose of anticoagulants 9. Patients who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of NAC e.g. expressing wish to self-discharge 10. Prisoners 11. Non-English speaking patients. (Study information material will only be produced in English in view of the known and stable demographic of the Edinburgh self harm population).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Paracetamol can be harmful to the liver when an excessive dose has been taken. To help prevent liver damage, an antidote known as acetylcysteine is given. However a few patients can develop liver damage even if they get acetylcysteine. This study will give a new drug (calmangafodipir - PP100-01) in combination with a new 12-hour regimen for giving acetylcysteine. The principal research question is does the combination of calmangafodipir and acetylcysteine produce any unexpected side-effects?; Secondary Objective: To see if there is any evidence that PP100-01 can prevent liver damage caused by paracetamol overdose by testing blood samples to look for specific substances called biomarkers which would help to show this. ;Primary end point(s): Adverse events and serious adverse events ; Timepoint(s) of evaluation of this end point: After each group there will be a review of the data by the DMC to approve commencement of the next group. • Group A: PP100-01 (2 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) • Group B: PP100-01 (5 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) • Group C: PP100-01 (10 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determine if there is evidence of PP100-01 having efficacy with regard to treatment of paracetamol-induced liver injury by measurement of conventional clinical biomarkers and novel experimental biomarkers. ; Timepoint(s) of evaluation of this end point: After each group there will be a review of the data by the DMC to approve commencement of the next group. • Group A: PP100-01 (2 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) • Group B: PP100-01 (5 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) • Group C: PP100-01 (10 µmol/kg calmangafodipir) after the “loading” dose of NAC (N=6) (N=2 NAC alone) | — |
Countries
United Kingdom
Contacts
Public ContactDennis Henriksen
PledPharma AB
Outcome results
None listed