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Completed

NCT Number: NCT03177395

PP100-01 (Calmangafodipir) for Overdose of Paracetamol

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.

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Key information

Conditions

Paracetamol Overdose

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Royal Infirmary of Edinburgh

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

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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).

Treatment and study plan

PP100-01 (calmangafodipir)

Drug

PP100-01

Other names: PP100-01

acetylcysteine

Drug

NAC

Other names: N-acetylcysteine

Primary outcomes

  1. Safety Events

    Time frame: 90 days

    Adverse Events and Serious Adverse Events

Secondary outcomes

  1. ALT(U/L)

    Time frame: Baseline

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

  2. ALT(U/L)

    Time frame: 10 hours

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

  3. ALT(U/L)

    Time frame: 20 hours

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

  4. INR

    Time frame: Baseline

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

  5. INR

    Time frame: 10 hours

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

  6. INR

    Time frame: 20 hours

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

  7. INR

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

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

  8. Additional NAC Infusion

    Time frame: Additional NAC at 12 hour

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

  9. K18 (U/L)

    Time frame: Baseline (2 hours)

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

  10. K18(U/L)

    Time frame: 10 hours

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

  11. K18 (U/L)

    Time frame: 20 hours

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

  12. K18 (U/L)

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

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

  13. ccK18 (U/L)

    Time frame: Baseline (2 hours)

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

  14. ccK18 (U/L)

    Time frame: 10 hours

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

  15. ccK18 (U/L)

    Time frame: 20 hours

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

  16. ccK18 (U/L)

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

    Caspace-cleaved Keratin-18

  17. miR-122 (Delta Count)

    Time frame: Baseline (2 hours)

    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

  18. miR-122 (Delta Count)

    Time frame: 10 hours

    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

  19. miR-122 (Delta Count)

    Time frame: 20 hours

    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

  20. miR-122 (Copies/mcL)

    Time frame: Baseline (2 h)

    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

  21. miR-122(Copies/mcL)

    Time frame: 10 hours

    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

  22. miR-122 (Copies/mcL)

    Time frame: 20 hours

    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

  23. miR-122 (Copies/mcL)

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

    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

Sponsors and collaborators

Lead sponsor

Egetis Therapeutics

Industry

Collaborators

  • NHS Lothian
  • University of Edinburgh

Registry information

Official study 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)

Acronym: POP

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jun 6, 2017
Registry last updated
Oct 3, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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