PP100-01 (Calmangafodipir) for Overdose of Paracetamol (POP)

Egetis Therapeutics

Status and phase: Completed; Phase 1

Conditions: Paracetamol Overdose

Treatments: Drug: Acetylcysteine; Drug: PP100-01 (calmangafodipir)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03177395

PP100-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Acetylcysteine (N-acetylcysteine; NAC)

No Intervention group

Description:

NAC infusion 100mg/kg in 200ml 'loading dose' at timepoint '0'. 12 hour NAC regime will be continued with the second dose: 200mg/kg NAC in 1000ml i.v. over 10hr as per standard care protocol in NHS Lothian.

PP100-01 (Calmangafodipir)+ NAC

Experimental group

Description:

In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: * Group A: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC * Group B: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC * Group C: PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes.

Treatment:

Drug: PP100-01 (calmangafodipir)

Drug: Acetylcysteine