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NCT04524442

Post-Authorization Safety Study (PASS) of LysaKare® in Adult Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients

Completed Phase 4 Results posted Last updated 24 January 2025
What this trial tests

Phase 4 trial testing arginine/lysine in Gastroenteropancreatic Neuroendocrine Tumors in 42 participants. Completed in 18 November 2023.

Timeline
25 January 2021
Primary endpoint
18 November 2023
18 November 2023

Quick facts

Lead sponsorAdvanced Accelerator Applications
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment42
Start date25 January 2021
Primary completion18 November 2023
Estimated completion18 November 2023
Sites7 locations across Italy, Netherlands, United Kingdom, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Advanced Accelerator Applications — full company profile →

Who can join

18 and older, any sex, with Gastroenteropancreatic Neuroendocrine Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in Serum Potassium Levels Over 24 Hours Primary · Day 0/Infusion Day (Hour 0, Hour 2, Hour 4, Hour 6, Hour 8, Hour 12, Hour 24)

Serum potassium levels at each collection time point will be measured at local laboratories of study sites using validated methods. The potassium concentration results will be summarized descriptively and will include mean change, maximum change, time to the maximum change, and the overall dynamics of the potassium concentration curve during and after the arginine/lysine infusion.

Pre-dose (hour 0)
GroupValue95% CI
GEP-NET4.3± 0.397
Change from Baseline (BL) to Hour 2
GroupValue95% CI
GEP-NET0.25± 0.452
Change from Baseline (BL) to Hour 4
GroupValue95% CI
GEP-NET0.60± 0.666
Change from Baseline (BL) to Hour 6
GroupValue95% CI
GEP-NET0.49± 0.602
Change from Baseline (BL) to Hour 8
GroupValue95% CI
GEP-NET0.38± 0.487
Change from Baseline (BL) to Hour 12
GroupValue95% CI
GEP-NET0.24± 0.557
Change from Baseline (BL) to Hour 24
GroupValue95% CI
GEP-NET0.07± 0.396
Percentage of Participants With Treatment Adverse Events (AEs) & Serious Adverse Events (SAEs) Secondary · Day 0/Infusion Day up to 48 hours post infusion

Safety measured by the percentage of participants with treatment emergent adverse events (starting from the signing of the ICF until the end of the follow-up call (48 hours after infusion).

Adverse Event (AEs)
GroupValue95% CI
GEP-NET11
Treatment-related AEs
GroupValue95% CI
GEP-NET6
Serious Adverse Events (SAEs)
GroupValue95% CI
GEP-NET0
Fatal SAEs
GroupValue95% CI
GEP-NET0
AEs leading to discontinuation
GroupValue95% CI
GEP-NET0
AEs leading to Interrruption
GroupValue95% CI
GEP-NET0
AEs requiring additional therapy
GroupValue95% CI
GEP-NET5
Treatment related AEs req. additional therapy
GroupValue95% CI
GEP-NET3
Number of Participants With Notable Changes in Vital Signs Secondary · Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)

Safety measured by the notable post-baseline changes in vital signs: (systolic blood pressure, diastolic blood pressure, pulse rate \& weight) compared to baseline.

Systolic blood pressure (mmHg): ≥180 with increase from baseline of ≥20
GroupValue95% CI
GEP-NET0
Systolic blood pressure (mmHg): ≤ 90 with decrease from baseline of ≥20
GroupValue95% CI
GEP-NET0
Diastolic blood pressure (mmHg): ≥105 with increase from baseline of ≥15
GroupValue95% CI
GEP-NET0
Diastolic blood pressure (mmHg): ≤ 50 with decrease from baseline of ≥15
GroupValue95% CI
GEP-NET0
Pulse rate (bpm): ≥100 with increase from baseline of >25%
GroupValue95% CI
GEP-NET0
Pulse rate (bpm): ≤ 50 with decrease from baseline of > 25%
GroupValue95% CI
GEP-NET0
Weight (kg): increase ≥10% from Baseline
GroupValue95% CI
GEP-NET0
Weight (kg): decrease > 10% from Baseline
GroupValue95% CI
GEP-NET0
Number of Participants With Notable Changes in Electrocardiogram (ECG) Secondary · Day 0/Infusion Day (0, 4, 8 and 24 hours)

Safety measured by the notable post-baseline changes in ECG values compared to baseline PR, QRS, QT, QTcF, and RR intervals were obtained from 12-lead ECGs for each subject during the study

QTcF (ms): Increase >30 to ≤ 60 ms
GroupValue95% CI
GEP-NET7
QTcF (ms): Increase >60 ms
GroupValue95% CI
GEP-NET0
QTcF (ms): New >450 to ≤ 480 ms
GroupValue95% CI
GEP-NET7
QTcF (ms): New >480 to ≤ 500 ms
GroupValue95% CI
GEP-NET0
QTcF (ms); New >500 ms
GroupValue95% CI
GEP-NET0
QT (ms): Increase >30 to ≤ 60 ms
GroupValue95% CI
GEP-NET9
QT (ms): Increase >60 ms
GroupValue95% CI
GEP-NET2
QT (ms): New >450 to ≤ 480 ms
GroupValue95% CI
GEP-NET6
Number of Participants With Notable Changes in Hematology Parameters Secondary · Day 0/Infusion Day (0 and 24 hours)

Safety measured by the notable post-baseline changes in Hematology parameters compared to baseline as represented by Shift tables based on common toxicity criteria (CTC) grades. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline.

GroupValue95% CI
GEP-NET0
Number of Participants With Notable Changes in Chemistry Parameters Secondary · Day 0/Infusion Day (0 and 24 hours)

Safety measured by the notable post-baseline changes in Chemistry parameters compared to baseline. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline. Key shifts were in the following parameters: creatinine, lactate dehydrogenase and creatinine clearance.

Creatinine (increase)
GroupValue95% CI
GEP-NET4
Lactate dehydrogenase (increase)
GroupValue95% CI
GEP-NET3
Creatinine clearance (decrease)
GroupValue95% CI
GEP-NET4
Number of Participants With Notable Changes in Electrolyte Parameters Secondary · Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)

Safety measured by the notable post-baseline changes in Electrolyte parameters compared to baseline. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline.

For Potassium (increase)
GroupValue95% CI
GEP-NET7
For sodium (decrease)
GroupValue95% CI
GEP-NET12
Mean Change From Baseline in Blood Gas Parameter, pH, Over 24 Hours Secondary · Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)

Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: pH.

Day 0/Infusion Day (Pre-dose) (hour 0)
GroupValue95% CI
GEP-NET7.35± 0.046
Change from Baseline (BL) to Hour 2
GroupValue95% CI
GEP-NET-0.03± 0.046
Change from Baseline (BL) to Hour 4
GroupValue95% CI
GEP-NET-0.06± 0.055
Change from Baseline (BL) to Hour 6
GroupValue95% CI
GEP-NET-0.05± 0.051
Change from Baseline (BL) to Hour 8
GroupValue95% CI
GEP-NET-0.05± 0.056
Change from Baseline (BL) to Hour 12
GroupValue95% CI
GEP-NET-0.03± 0.054
Change from Baseline (BL) to Hour 24
GroupValue95% CI
GEP-NET-0.04± 0.051
Mean Change From Baseline in Blood Gas Parameter, Lactic Acid, Over 24 Hours Secondary · Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)

Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Lactic Acid

Day 0/Infusion Day (Pre-dose) (hour 0)
GroupValue95% CI
GEP-NET1.40± 0.604
Change from Baseline (BL) to Hour 2
GroupValue95% CI
GEP-NET-0.07± 0.671
Change from Baseline (BL) to Hour 4
GroupValue95% CI
GEP-NET-0.23± 0.523
Change from Baseline (BL) to Hour 6
GroupValue95% CI
GEP-NET-0.26± 0.546
Change from Baseline (BL) to Hour 8
GroupValue95% CI
GEP-NET-0.19± 0.465
Change from Baseline (BL) to Hour 12
GroupValue95% CI
GEP-NET-0.21± 0.657
Change from Baseline (BL) to Hour 24
GroupValue95% CI
GEP-NET-0.16± 0.650
Mean Change From Baseline in Blood Gas Parameter, Partial Pressure Carbon Dioxide, Over 24 Hours Secondary · Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)

Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Partial Pressure Carbon Dioxide.

Day 0/Infusion Day (Pre-dose) (hour 0)
GroupValue95% CI
GEP-NET50.53± 8.712
Change from Baseline (BL) to Hour 2
GroupValue95% CI
GEP-NET-1.08± 6.670
Change from Baseline (BL) to Hour 4
GroupValue95% CI
GEP-NET-2.44± 8.717
Change from Baseline (BL) to Hour 6
GroupValue95% CI
GEP-NET-4.90± 8.507
Change from Baseline (BL) to Hour 8
GroupValue95% CI
GEP-NET-4.87± 8.399
Change from Baseline (BL) to Hour 12
GroupValue95% CI
GEP-NET-5.71± 8.002
Change from Baseline (BL) to Hour 24
GroupValue95% CI
GEP-NET-2.54± 8.242

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were collected from the administration of the study treatment up to 48 hours in addition to the infusion time, an average of 52 hours total.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

All Participants
Serious: 0/41 (0%)
Deaths: 0/41
Other adverse events (10 terms — click to expand)

ReactionSystemAll Participants
HyperkalaemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Abdominal painGastrointestinal disorders
ProctalgiaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
ContusionInjury, poisoning and procedural complications
DizzinessNervous system disorders
HeadacheNervous system disorders
Respiratory acidosisRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT04524442 adverse events section.

Sponsor's own description

The purpose of the study was to evaluate the effect of arginine/lysine solution administration on serum potassium levels. A systematic assessment of serum potassium levels was performed during infusion and up to 24 hours post start of infusion compared to baseline.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. An Update of G-Protein-Coupled Receptor Signaling and Its Deregulation in Gastric Carcinogenesis.
    Yan H, Zhang JL, Leung KT, Lo KW, et al · · 2023 · cited 8× · PMID 36765694 · DOI 10.3390/cancers15030736

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04524442.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing