Paracetamol OverdosePhase 1POPNCT03177395
PP100-01 (Calmangafodipir) for Overdose of Paracetamol
A Phase 1 study testing PP100-01 (calmangafodipir) and Acetylcysteine in people with Paracetamol Overdose, run by Egetis Therapeutics AB (publ) at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Paracetamol Overdose
- What is being tested?
- PP100-01 (calmangafodipir) and Acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Jun 2017to 8 Nov 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Infirmary of Edinburgh
Edinburgh, City Of Edinburgh, EH16 4SA
About this study
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)
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.
Read the 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.
- Conditions
- Paracetamol Overdose
- Being tested
- PP100-01 (calmangafodipir), Acetylcysteine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PP100-01 (calmangafodipir)Drug
Also called PP100-01
PP100-01
AcetylcysteineDrug
Also called N-acetylcysteine
NAC
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: PP100-01 (calmangafodipir); Drug: Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Events
Adverse Events and Serious Adverse Events
Measured: 90 days
Secondary outcomes (23)
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Measured: Baseline
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Measured: 10 hours
ALT(U/L)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
Measured: 20 hours
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Measured: Baseline
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Measured: 10 hours
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Measured: 20 hours
INR
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
Measured: value at 20 hours divided by baseline value for each patient
Additional NAC Infusion
participants required additional NAC infusions after the 12-hour NAC regimen
Measured: Additional NAC at 12 hour
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Measured: Baseline (2 hours)
K18(U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Measured: 10 hours
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Measured: 20 hours
K18 (U/L)
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
Measured: Ratio - value at 20 hours divided by baseline value for each patient
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Measured: Baseline (2 hours)
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Measured: 10 hours
ccK18 (U/L)
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
Measured: 20 hours
ccK18 (U/L)
Caspace-cleaved Keratin-18
Measured: Ratio - value at 20 hours divided by baseline value for each patient
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
Measured: Baseline (2 hours)
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
Measured: 10 hours
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
Measured: 20 hours
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
Measured: Baseline (2 h)
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
Measured: 10 hours
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
Measured: 20 hours
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
Measured: Ratio - value at 20 hours divided by baseline value for each patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study start8 Jun 2017
- Primary completion8 Aug 2018
- Study completion8 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Paracetamol OverdoseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Egetis Therapeutics AB (publ)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Edinburgh, NHS Lothian
- Responsible party
- Sponsor
- Investigators
- James Dear, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03177395
- Sponsor's protocol ID
- PP100-001
- Acronym
- POP
- Status last verified
- Sep 2019
- First submitted
- 23 May 2017
- Last updated
- 3 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31311721POP 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.
PubMed 30621764
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03177395
- Acronym / sponsor ID
- POP / PP100-001
- Conditions
- Paracetamol Overdose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Egetis Therapeutics AB (publ)Industry (pharma, biotech, devices)
- Collaborators
- University of Edinburgh, NHS Lothian
- Study start
- 8 Jun 2017 (actual)
- Primary completion
- 8 Aug 2018 (actual)
- Study completion
- 8 Nov 2018 (actual)
- First posted
- 6 Jun 2017 (actual)
- Results
- Posted 3 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: PP100-01 (calmangafodipir), Drug: AcetylcysteineIn 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PP100-01 (calmangafodipir)Also: PP100-01PP100-01 | Drug | PP100-01 (Calmangafodipir)+ NAC |
| AcetylcysteineAlso: N-acetylcysteineNAC | Drug | PP100-01 (Calmangafodipir)+ NAC |
Primary outcome
Safety Events
Time frame: 90 days
Adverse Events and Serious Adverse Events
23 secondary outcomes
ALT(U/L)
Time frame: Baseline
ALT(U/L)
Time frame: 10 hours
ALT(U/L)
Time frame: 20 hours
INR
Time frame: Baseline
INR
Time frame: 10 hours
INR
Time frame: 20 hours
INR
Time frame: value at 20 hours divided by baseline value for each patient
Additional NAC Infusion
Time frame: Additional NAC at 12 hour
K18 (U/L)
Time frame: Baseline (2 hours)
K18(U/L)
Time frame: 10 hours
K18 (U/L)
Time frame: 20 hours
K18 (U/L)
Time frame: Ratio - value at 20 hours divided by baseline value for each patient
ccK18 (U/L)
Time frame: Baseline (2 hours)
ccK18 (U/L)
Time frame: 10 hours
ccK18 (U/L)
Time frame: 20 hours
ccK18 (U/L)
Time frame: Ratio - value at 20 hours divided by baseline value for each patient
miR-122 (Delta Count)
Time frame: Baseline (2 hours)
miR-122 (Delta Count)
Time frame: 10 hours
miR-122 (Delta Count)
Time frame: 20 hours
miR-122 (Copies/mcL)
Time frame: Baseline (2 h)
miR-122(Copies/mcL)
Time frame: 10 hours
miR-122 (Copies/mcL)
Time frame: 20 hours
miR-122 (Copies/mcL)
Time frame: Ratio - value at 20 hours divided by baseline value for each patient
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31311721Morrison 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.
- Derived from this study: PubMed 30621764POP 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Dear principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PP100-01 (calmangafodipir) and Acetylcysteine in people with Paracetamol Overdose, run by Egetis Therapeutics AB (publ) at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Events (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03177395, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2019.