PP100-01 (Calmangafodipir) for Overdose of Paracetamol

NCT03177395 | Completed Phase 1 Results DMC

• 1 other identifier: PP100-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Paracetamol Overdose

Outcome Measures

Primary Outcomes (1)

• Safety Events

  Adverse Events and Serious Adverse Events

  90 days

Secondary Outcomes (23)

• ALT(U/L)

  Baseline

• ALT(U/L)

  10 hours

• ALT(U/L)

  20 hours

• INR

  Baseline

• INR

  10 hours

Study Arms (2)

Acetylcysteine (N-acetylcysteine; NAC)

NO INTERVENTION

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

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.

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

Interventions

PP100-01 (calmangafodipir) DRUG

PP100-01

Also known as: PP100-01

PP100-01 (Calmangafodipir)+ NAC

Acetylcysteine DRUG

NAC

Also known as: N-acetylcysteine

PP100-01 (Calmangafodipir)+ NAC

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Provision of written informed consent
• Males and females of at least 16 years of age

You may not qualify if:

• Patients that do not have the capacity to consent to participate in the study
• Patients detained under the Mental Health Act or deemed unfit by the Investigator to participate due to mental health.
• Patients with known permanent cognitive impairment
• Patients who are pregnant or nursing
• Patients who have previously participated in the study
• Unreliable history of POD
• Patients presenting after 24hrs of POD
• Patients who take anticoagulants (e.g. warfarin) therapeutically or have taken an overdose of anticoagulants
• 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
• Prisoners
• 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).

Sponsors & Collaborators

• Egetis Therapeutics: lead
• University of Edinburgh: collaborator
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, City Of Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31311721 DERIVED

• 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.

  PMID: 30621764 DERIVED

MeSH Terms

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; Acetylcysteine

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr James Dear
• Organization: Pharmacology, Therapeutics and Toxicology Unit, Centre for Cardiovascular Science, University of Edinburgh, UK

james.dear@ed.ac.uk

+44(0)131 242 9214

Study Officials

• James Dear

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: June 6, 2017
• Study Start: June 8, 2017
• Primary Completion: August 8, 2018
• Study Completion: November 8, 2018
• Last Updated: October 3, 2019
• Results First Posted: October 3, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)