PP100-01 (Calmangafodipir) for Overdose of Paracetamol

Egetis Therapeutics24 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Paracetamol Overdose

Interventions

PP100-01 (calmangafodipir)DRUG

PP100-01

AcetylcysteineDRUG

NAC

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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).

Locations (1)

Royal Infirmary of Edinburgh

Edinburgh, City Of Edinburgh, United Kingdom

Outcomes

Primary Outcomes

Safety Events

Adverse Events and Serious Adverse Events

Time frame: 90 days

Secondary Outcomes

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.

Time frame: Baseline

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.

Time frame: 10 hours

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.

Time frame: 20 hours

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)

Time frame: Baseline

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)

Time frame: 10 hours

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)

Time frame: 20 hours

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)

Time frame: value at 20 hours divided by baseline value for each patient

Additional NAC Infusion

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

participants required additional NAC infusions after the 12-hour NAC regimen

Time frame: Additional NAC at 12 hour

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.

Time frame: Baseline (2 hours)

K18(U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.

Time frame: 10 hours

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.

Time frame: 20 hours

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.

Time frame: Ratio - value at 20 hours divided by baseline value for each patient

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).

Time frame: Baseline (2 hours)

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).

Time frame: 10 hours

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).

Time frame: 20 hours

ccK18 (U/L)

Caspace-cleaved Keratin-18

Time frame: Ratio - value at 20 hours divided by baseline value for each patient

miR-122 (Delta Count)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose

Time frame: Baseline (2 hours)

miR-122 (Delta Count)

Time frame: 10 hours

miR-122 (Delta Count)

Time frame: 20 hours

miR-122 (Copies/mcL)

Time frame: Baseline (2 h)

miR-122(Copies/mcL)

Time frame: 10 hours

miR-122 (Copies/mcL)

Time frame: 20 hours

miR-122 (Copies/mcL)

Time frame: Ratio - value at 20 hours divided by baseline value for each patient