PP100-01 (Calmangafodipir) for Overdose of Paracetamol

Paracetamol Overdose Clinical Trial

— POP  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03177395
• Other study ID #: PP100-001
• Status: Completed
• Phase: Phase 1
• Start date: June 8, 2017
• Est. completion date: November 8, 2018

Study information

• Verified date: September 2019
• Source: PledPharma AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 8, 2018
• Est. primary completion date: August 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Drug Overdose
• Paracetamol Overdose

Intervention

Drug:
• PP100-01 (calmangafodipir)
PP100-01
• Acetylcysteine
NAC

Locations

Country	Name	City	State
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh	City Of Edinburgh

Sponsors (3)

Lead Sponsor	Collaborator
PledPharma AB	NHS Lothian, University of Edinburgh

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Events	Adverse Events and Serious Adverse Events	90 days
Secondary	ALT(U/L)	The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.	Baseline
Secondary	ALT(U/L)	The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.	10 hours
Secondary	ALT(U/L)	The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.	20 hours
Secondary	INR	international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)	Baseline
Secondary	INR	international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)	10 hours
Secondary	INR	international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)	20 hours
Secondary	INR	international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)	value at 20 hours divided by baseline value for each patient
Secondary	Additional NAC Infusion	participants required additional NAC infusions after the 12-hour NAC regimen	Additional NAC at 12 hour
Secondary	K18 (U/L)	In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.	Baseline (2 hours)
Secondary	K18(U/L)	In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.	10 hours
Secondary	K18 (U/L)	In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.	20 hours
Secondary	K18 (U/L)	In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.	Ratio - value at 20 hours divided by baseline value for each patient
Secondary	ccK18 (U/L)	The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).	Baseline (2 hours)
Secondary	ccK18 (U/L)	The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).	10 hours
Secondary	ccK18 (U/L)	The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).	20 hours
Secondary	ccK18 (U/L)	Caspace-cleaved Keratin-18	Ratio - value at 20 hours divided by baseline value for each patient
Secondary	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	Baseline (2 hours)
Secondary	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	10 hours
Secondary	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	20 hours
Secondary	miR-122 (Copies/mcL)	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	Baseline (2 h)
Secondary	miR-122(Copies/mcL)	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	10 hours
Secondary	miR-122 (Copies/mcL)	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 hours
Secondary	miR-122 (Copies/mcL)	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	Ratio - value at 20 hours divided by baseline value for each patient