Clinical trial NCT03177395: PP100-01 (Calmangafodipir) for Overdose of Paracetamol
Official 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 (The POP Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Paracetamol Overdose
Lead sponsor: Egetis Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of Edinburgh
name: NHS Lothian
First posted: 2017-06-06
Enrollment: 24
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigate the safety and tolerability of PP100-01 add-on treatment to the 12hr NAC treatment regime in patients treated for paracetamol/acetaminophen overdose (POD) when NAC treatment is initiated before 24hours post POD.

Detailed description: The study will be an open label, randomised, exploratory, rising dose design, NAC controlled, phase 1 safety and tolerability study in patients treated with NAC for paracetamol/acetaminophen overdose.

Entry into the study will depend on the patient's blood results confirming the need for NAC. A total of 24 patients will be assigned into one of 3 dosing cohorts of 8 patients (N=6 for PP100-01 and NAC; N=2 for NAC alone).

The study will primarily evaluate safety and tolerability for treatment with PP100-01 in combination with NAC as compared to NAC alone.

Eligibility criteria: Inclusion Criteria:

1. Any patient with capacity admitted to hospital within 24 hrs either a single acute POD or more than one dose of paracetamol (staggered) and deemed to require treatment with NAC.
2. Provision of written informed consent
3. Males and females of at least 16 years of age

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 POD
7. Patients presenting after 24hrs of POD
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).

Primary outcomes:
measure: Safety Events
timeFrame: 90 days
Secondary outcomes:
measure: ALT(U/L)
timeFrame: Baseline
measure: ALT(U/L)
timeFrame: 10 hours
measure: ALT(U/L)
timeFrame: 20 hours
measure: INR
timeFrame: Baseline
measure: INR
timeFrame: 10 hours
measure: INR
timeFrame: 20 hours
measure: INR
timeFrame: value at 20 hours divided by baseline value for each patient
measure: Additional NAC Infusion
timeFrame: Additional NAC at 12 hour
measure: K18 (U/L)
timeFrame: Baseline (2 hours)
measure: K18(U/L)
timeFrame: 10 hours
measure: K18 (U/L)
timeFrame: 20 hours
measure: K18 (U/L)
timeFrame: Ratio - value at 20 hours divided by baseline value for each patient
measure: ccK18 (U/L)
timeFrame: Baseline (2 hours)
measure: ccK18 (U/L)
timeFrame: 10 hours
measure: ccK18 (U/L)
timeFrame: 20 hours
measure: ccK18 (U/L)
timeFrame: Ratio - value at 20 hours divided by baseline value for each patient
measure: miR-122 (Delta Count)
timeFrame: Baseline (2 hours)
measure: miR-122 (Delta Count)
timeFrame: 10 hours
measure: miR-122 (Delta Count)
timeFrame: 20 hours
measure: miR-122 (Copies/mcL)
timeFrame: Baseline (2 h)
measure: miR-122(Copies/mcL)
timeFrame: 10 hours
measure: miR-122 (Copies/mcL)
timeFrame: 20 hours
measure: miR-122 (Copies/mcL)
timeFrame: Ratio - value at 20 hours divided by baseline value for each patient
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: City Of Edinburgh
Study officials:
affiliation: University of Edinburgh
name: James Dear
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morrison EE, Oatey K, Gallagher B, Grahamslaw J, O'Brien R, Black P, Oosthuyzen W, Lee RJ, Weir CJ, Henriksen D, Dear JW; POP Trial Investigators. Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial). EBioMedicine. 2019 Aug;46:423-430. doi: 10.1016/j.ebiom.2019.07.013. Epub 2019 Jul 13.
citation: POP Trial Investigators; Dear J. Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose-the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial. Trials. 2019 Jan 8;20(1):27. doi: 10.1186/s13063-018-3134-1.