POP: PP100-01 (Calmangafodipir) for Overdose of Paracetamol
Sponsor
Egetis Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03177395
Collaborator
University of Edinburgh (Other), NHS Lothian (Other)
24
1
2
17
1.4
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Study Type:
Interventional
Actual Enrollment
:
24 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date
:
Jun 8, 2017
Actual Primary Completion Date
:
Aug 8, 2018
Actual Study Completion Date
:
Nov 8, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Acetylcysteine (N-acetylcysteine; NAC) 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. |
|
| Experimental: PP100-01 (Calmangafodipir)+ NAC 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)
PP100-01
Other Names:
Drug: Acetylcysteine
NAC
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety Events [90 days]
Adverse Events and Serious Adverse Events
Secondary Outcome Measures
- ALT(U/L) [Baseline]
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
- ALT(U/L) [10 hours]
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
- ALT(U/L) [20 hours]
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage.
- INR [Baseline]
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
- INR [10 hours]
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
- INR [20 hours]
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
- INR [value at 20 hours divided by baseline value for each patient]
international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF)
- Additional NAC Infusion [Additional NAC at 12 hour]
participants required additional NAC infusions after the 12-hour NAC regimen
- K18 (U/L) [Baseline (2 hours)]
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
- K18(U/L) [10 hours]
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
- K18 (U/L) [20 hours]
In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death.
- K18 (U/L) [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.
- ccK18 (U/L) [Baseline (2 hours)]
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
- ccK18 (U/L) [10 hours]
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
- ccK18 (U/L) [20 hours]
The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death).
- ccK18 (U/L) [Ratio - value at 20 hours divided by baseline value for each patient]
Caspace-cleaved Keratin-18
- miR-122 (Delta Count) [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
- miR-122 (Delta Count) [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
- miR-122 (Delta Count) [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
- miR-122 (Copies/mcL) [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
- miR-122(Copies/mcL) [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
- miR-122 (Copies/mcL) [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
- miR-122 (Copies/mcL) [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
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Infirmary of Edinburgh | Edinburgh | City Of Edinburgh | United Kingdom | EH16 4SA |
Sponsors and Collaborators
- Egetis Therapeutics
- University of Edinburgh
- NHS Lothian
Investigators
- Principal Investigator: James Dear, University of Edinburgh
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Egetis Therapeutics
ClinicalTrials.gov Identifier:
NCT03177395
Other Study ID Numbers:
- PP100-001
First Posted:
Jun 6, 2017
Last Update Posted:
Oct 3, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Studied period: 05 June 2017 to 08 August 2018 Study centres: Edinburgh Clinical Trials Unit (ECTU) The Emergency Medicine Research Group Edinburgh (EMERGE) |
|---|---|
| Pre-assignment Detail | Adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n=6/dose) or NAC alone (n=2). Calmangafodipir doses were 2, 5, or 10 μmol/kg. Participants, study and clinical teams not blinded |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 μmol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 μmol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 μmol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 μmol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 μmol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (10 μmol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 6 | 6 | 6 |
| COMPLETED | 6 | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC | Total |
|---|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: • Group B: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 24 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
6
100%
|
5
83.3%
|
6
100%
|
6
100%
|
23
95.8%
|
| >=65 years |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
4.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
32.2
(12.5)
|
42.5
(13.1)
|
42.7
(12.7)
|
22.7
(3.3)
|
35.0
(13.4)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
4
66.7%
|
4
66.7%
|
3
50%
|
13
54.2%
|
| Male |
4
66.7%
|
2
33.3%
|
2
33.3%
|
3
50%
|
11
45.8%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
1
4.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
5
83.3%
|
6
100%
|
6
100%
|
6
100%
|
23
95.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||
| United Kingdom |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
24
100%
|
| Time from ingestion of paracetamol to hospital presentation (hours) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [hours] |
8.8
(6.2)
|
6.0
(6.2)
|
5.8
(7.2)
|
4.9
(5.2)
|
6.4
(6.2)
|
| Type of overdose (Count of Participants) | |||||
| Acute, ≤8 h to NAC |
2
33.3%
|
4
66.7%
|
4
66.7%
|
4
66.7%
|
14
58.3%
|
| Acute, >8 h to NAC |
3
50%
|
2
33.3%
|
2
33.3%
|
1
16.7%
|
8
33.3%
|
| Staggered intentional |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
4.2%
|
| Supra-therapeutic |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
1
4.2%
|
| Presentation paracetamol concentration (mg/L) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/L] |
76
(81)
|
127
(90)
|
74
(44)
|
127
(47)
|
101
(66)
|
| Total paracetamol ingested (mg/kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/kg] |
185
(156)
|
235
(77)
|
229
(72)
|
397
(476)
|
262
(195)
|
| Time from ingestion of paracetamol to start of NAC treatment (hours) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [hours] |
12.1
(5.2)
|
9.8
(6.5)
|
10.2
(6.9)
|
8.6
(4.1)
|
10.2
(5.7)
|
| Time from ingestion of paracetamol to start of calmangafodipir (hours) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [hours] |
NA
(NA)
|
12.6
(6.8)
|
10.8
(4.1)
|
11.8
(5.4)
|
11.7
(5.4)
|
| Any other drug ingested (Count of Participants) | |||||
| Yes |
5
83.3%
|
4
66.7%
|
5
83.3%
|
5
83.3%
|
19
79.2%
|
| No |
1
16.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
5
20.8%
|
| Serum creatinine (μmol/L) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [μmol/L] |
74.7
(11.0)
|
67.5
(13.3)
|
67.3
(17.2)
|
69.5
(13.1)
|
69.8
(13.6)
|
Outcome Measures
| Title | Safety Events |
|---|---|
| Description | Adverse Events and Serious Adverse Events |
| Time Frame | 90 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| In addition to paracetamol overdose, 19 out of the 24 randomised participants reported taking overdoses of other medicines in addition to the paracetamol. All treatment groups included participants with paracetamol only overdoses and mixed overdoses |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | 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 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. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Any Adverse event |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
| Any serious adverse event |
2
33.3%
|
4
66.7%
|
2
33.3%
|
3
50%
|
| Adverse event after commencement of NAC treatment |
6
100%
|
5
83.3%
|
6
100%
|
6
100%
|
| Serious AE after commencement of NAC treatment |
1
16.7%
|
1
16.7%
|
1
16.7%
|
2
33.3%
|
| Adverse event where outcome was death |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Adverse event unrelated to NAC |
3
50%
|
5
83.3%
|
3
50%
|
5
83.3%
|
| Adverse event possibly related to NAC |
2
33.3%
|
2
33.3%
|
2
33.3%
|
2
33.3%
|
| Adverse event probably related to NAC |
3
50%
|
2
33.3%
|
3
50%
|
2
33.3%
|
| Adverse event definitely related to NAC |
2
33.3%
|
3
50%
|
1
16.7%
|
1
16.7%
|
| Adverse event unrelated to PP100-01 |
6
100%
|
6
100%
|
5
83.3%
|
6
100%
|
| Adverse event possibly related to PP100-01 |
0
0%
|
4
66.7%
|
2
33.3%
|
2
33.3%
|
| Adverse event probably related to PP100-01 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Adverse event definitely related to PP100-01 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Any suspected unexpected serious adverse reaction |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| SUSAR to NAC |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SUSAR to PP100-01 |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| SUSAR to NAC and PP100-01 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | ALT(U/L) |
|---|---|
| Description | The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
42.5
(3.6)
|
24.6
(2.1)
|
29.4
(2.3)
|
17.7
(1.5)
|
| Title | ALT(U/L) |
|---|---|
| Description | The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. |
| Time Frame | 10 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 24 participants received the full dose of PP100-01 according to the allocated dosing cohort, all participants received as a minimum 12 hours of NAC treatment (loading dose, plus further 10 hours). For both PP100-01 and NAC total dose was adjusted according to participant weight |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
41.4
(3.3)
|
22.9
(1.8)
|
25.3
(2.1)
|
15.0
(1.3)
|
| Title | ALT(U/L) |
|---|---|
| Description | The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. |
| Time Frame | 20 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 24 participants received the full dose of PP100-01 according to the allocated dosing cohort, all participants received as a minimum 12 hours of NAC treatment (loading dose, plus further 10 hours). For both PP100-01 and NAC total dose was adjusted according to participant weight |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
43.3
(3.8)
|
20.4
(1.9)
|
25.4
(1.8)
|
16.4
(1.5)
|
| Title | INR |
|---|---|
| Description | international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 24 participants received the full dose of PP100-01 according to the allocated dosing cohort, all participants received as a minimum 12 hours of NAC treatment (loading dose, plus further 10 hours). For both PP100-01 and NAC total dose was adjusted according to participant weight |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [ratio] |
1.02
(0.04)
|
1.00
(0.12)
|
0.98
(0.04)
|
1.05
(0.14)
|
| Title | INR |
|---|---|
| Description | international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) |
| Time Frame | 10 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [ratio] |
1.30
(0.18)
|
1.17
(0.20)
|
1.20
(0.00)
|
1.22
(0.25)
|
| Title | INR |
|---|---|
| Description | international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) |
| Time Frame | 20 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [ratio] |
1.18
(0.21)
|
1.07
(0.19)
|
1.08
(0.04)
|
1.22
(1.17)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 5 | 6 | 6 |
| Geometric Mean (Standard Deviation) [ratio] |
1.15
(1.17)
|
1.07
(1.12)
|
1.10
(1.07)
|
1.10
(1.10)
|
| Title | Additional NAC Infusion |
|---|---|
| Description | participants required additional NAC infusions after the 12-hour NAC regimen |
| Time Frame | Additional NAC at 12 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| None |
3
50%
|
5
83.3%
|
6
100%
|
6
100%
|
| One |
1
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
| Two |
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
187
(2.20)
|
177
(1.82)
|
193
(1.56)
|
128
(1.25)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
182
(1.95)
|
152
(1.56)
|
170
(1.42)
|
111
(1.18)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
347
(3.18)
|
229
(1.94)
|
172
(1.45)
|
181
(1.73)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
1.85
(1.47)
|
1.29
(1.89)
|
0.89
(1.57)
|
1.41
(1.83)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
67
(1.99)
|
45
(1.33)
|
84
(1.80)
|
104
(2.44)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
72
(2.24)
|
53
(1.25)
|
56
(1.57)
|
78
(2.12)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
149
(3.34)
|
66
(1.34)
|
85
(1.62)
|
111
(2.56)
|
| Title | ccK18 (U/L) |
|---|---|
| Description | Caspace-cleaved Keratin-18 |
| Time Frame | Ratio - value at 20 hours divided by baseline value for each patient |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [U/L] |
2.22
(1.77)
|
1.49
(1.55)
|
1.02
(1.79)
|
1.08
(2.44)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [DCt] |
5.58
(3.36)
|
5.85
(1.50)
|
4.43
(3.92)
|
8.73
(2.36)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [DCt] |
5.41
(3.86)
|
6.14
(1.99)
|
5.01
(3.36)
|
9.00
(1.45)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [DCt] |
4.85
(3.97)
|
7.12
(2.26)
|
4.49
(2.93)
|
8.44
(1.50)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [copies/mcL] |
146,363
(11.7)
|
116,749
(2.4)
|
194,075
(13.5)
|
36,051
(3.9)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [copies/mcL] |
206,205
(13.0)
|
109,882
(3.3)
|
196,732
(9.4)
|
37,066
(2.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [copies/mcL] |
216,256
(10.8)
|
57,664
(3.8)
|
202,271
(7.7)
|
40,745
(3.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC |
|---|---|---|---|---|
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Standard Deviation) [copies/mcL] |
1.48
(5.71)
|
0.49
(1.98)
|
1.04
(8.28)
|
1.13
(2.96)
|
Adverse Events
| Time Frame | Adverse events / adverse reactions were assessed at baseline, 2, 2.5, 10, 20 and 22 hours as well as ad hoc and as part of follow up. Following discharge, patients were followed up using their electronic records. AE data were collected 7, 30 and 90 days after randomisation | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC | ||||
| Arm/Group 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: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC PP100-01 treatment is administered intravenously over 5 minutes. PP100-01 (calmangafodipir): PP100-01 | ||||
All Cause Mortality |
||||||||
| Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||
Serious Adverse Events |
||||||||
| Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 4/6 (66.7%) | 2/6 (33.3%) | 3/6 (50%) | ||||
| Cardiac disorders | ||||||||
| cardiac disorders | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Gastrointestinal disorders | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||||||
| Infections and infestations | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 |
| Injury, poisoning and procedural complications | ||||||||
| Injury, poisoning and procedural complications | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||||||||
| Nervous system disorders | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Psychiatric disorders | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||
| Vascular disorders | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Acetylcysteine (N-acetylcysteine; NAC) | Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC | Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC | Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | ||||
| Cardiac disorders | ||||||||
| Ventricular extrasystoles | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Tachycardia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| heart block | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 3/6 (50%) | 4 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 3/6 (50%) | 3 |
| vomiting | 4/6 (66.7%) | 4 | 4/6 (66.7%) | 7 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 |
| abdominal pain | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 |
| Retching | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Hypoaethesia oral | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| General disorders | ||||||||
| Pyrexia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| chest pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||||||
| Otitis externa | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Pneumonia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Tubo-ovarian abscess | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pharyngitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Pyelonephritis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Overdose | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 |
| Fall | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Soft tissue injury | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| ntentional product misuse | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Hypokalemia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back Pain | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 |
| Headache | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 |
| migraine | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Alcohol withdrawal syndrome | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Anxiety | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| substance abuse | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Renal and urinary disorders | ||||||||
| Dysuria | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Respiration abnormal | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Wheezing | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 |
| Dyspnoea | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Hyperhidrosis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypotension | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr James Dear |
|---|---|
| Organization | Pharmacology, Therapeutics and Toxicology Unit, Centre for Cardiovascular Science, University of Edinburgh, UK |
| Phone | +44(0)131 242 9214 |
| james.dear@ed.ac.uk |
Responsible Party:
Egetis Therapeutics
ClinicalTrials.gov Identifier:
NCT03177395
Other Study ID Numbers:
- PP100-001
First Posted:
Jun 6, 2017
Last Update Posted:
Oct 3, 2019
Last Verified:
Sep 1, 2019