Back to resultsPP100-01 (Calmangafodipir) for Overdose of Paracetamol (POP)
Primary Purpose
Paracetamol Overdose
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
PP100-01 (calmangafodipir)
Acetylcysteine
Sponsored by
About this trial
This is an interventional treatment trial for Paracetamol Overdose
Eligibility Criteria
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).
Sites / Locations
- Royal Infirmary of Edinburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Acetylcysteine (N-acetylcysteine; NAC)
PP100-01 (Calmangafodipir)+ NAC
Arm 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.
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.
Outcomes
Primary Outcome Measures
Safety Events
Adverse Events and Serious Adverse Events
Secondary Outcome Measures
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Additional NAC Infusion
participants required additional NAC infusions after the 12-hour NAC regimen
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
K18(U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
ccK18 (U/L)
Caspace-cleaved Keratin-18
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
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
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
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
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
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
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
Full Information
NCT ID
NCT03177395
First Posted
May 23, 2017
Last Updated
September 10, 2019
Sponsor
Egetis Therapeutics
Collaborators
University of Edinburgh, NHS Lothian
1. Study Identification
Unique Protocol Identification Number
NCT03177395
Brief Title
PP100-01 (Calmangafodipir) for Overdose of Paracetamol
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
June 8, 2017 (Actual)
Primary Completion Date
August 8, 2018 (Actual)
Study Completion Date
November 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Egetis Therapeutics
Collaborators
University of Edinburgh, NHS Lothian
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paracetamol Overdose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acetylcysteine (N-acetylcysteine; NAC)
Arm Type
No Intervention
Arm 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.
Arm Title
PP100-01 (Calmangafodipir)+ NAC
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
PP100-01 (calmangafodipir)
Other Intervention Name(s)
PP100-01
Intervention Description
PP100-01
Intervention Type
Drug
Intervention Name(s)
Acetylcysteine
Other Intervention Name(s)
N-acetylcysteine
Intervention Description
NAC
Primary Outcome Measure Information:
Title
Safety Events
Description
Adverse Events and Serious Adverse Events
Time Frame
90 days
Secondary Outcome Measure Information:
Title
ALT(U/L)
Description
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Time Frame
Baseline
Title
ALT(U/L)
Description
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Time Frame
10 hours
Title
ALT(U/L)
Description
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Time Frame
20 hours
Title
INR
Description
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Time Frame
Baseline
Title
INR
Description
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Time Frame
10 hours
Title
INR
Description
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Time Frame
20 hours
Title
INR
Description
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
Title
Additional NAC Infusion
Description
participants required additional NAC infusions after the 12-hour NAC regimen
Time Frame
Additional NAC at 12 hour
Title
K18 (U/L)
Description
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Time Frame
Baseline (2 hours)
Title
K18(U/L)
Description
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Time Frame
10 hours
Title
K18 (U/L)
Description
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Time Frame
20 hours
Title
K18 (U/L)
Description
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
Title
ccK18 (U/L)
Description
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Time Frame
Baseline (2 hours)
Title
ccK18 (U/L)
Description
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Time Frame
10 hours
Title
ccK18 (U/L)
Description
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Time Frame
20 hours
Title
ccK18 (U/L)
Description
Caspace-cleaved Keratin-18
Time Frame
Ratio - value at 20 hours divided by baseline value for each patient
Title
miR-122 (Delta Count)
Description
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)
Title
miR-122 (Delta Count)
Description
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
10 hours
Title
miR-122 (Delta Count)
Description
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
20 hours
Title
miR-122 (Copies/mcL)
Description
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 h)
Title
miR-122(Copies/mcL)
Description
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
10 hours
Title
miR-122 (Copies/mcL)
Description
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
20 hours
Title
miR-122 (Copies/mcL)
Description
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
Ratio - value at 20 hours divided by baseline value for each patient
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Dear
Organizational Affiliation
University of Edinburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Infirmary of Edinburgh
City
Edinburgh
State/Province
City Of Edinburgh
ZIP/Postal Code
EH16 4SA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31311721
Citation
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.
Results Reference
derived
PubMed Identifier
30621764
Citation
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.
Results Reference
derived
Learn more about this trial
PP100-01 (Calmangafodipir) for Overdose of Paracetamol
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