Trial reportCurrent pharmaceutical design2013
Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers.
Trial report in Current pharmaceutical design, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of 3K3A-APC, a Recombinant Variant of Human Activated Protein C (APC), in Healthy Adult Volunteers
A Multi-center, Phase 2 Study Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC in Combination With tPA, Mechanical Thrombectomy or Both in Moderate to Severe Acute Ischemic Stroke
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Trial
- Selecting Patients for Intra-Arterial Therapy in the Context of a Clinical Trial for Neuroprotection.Stroke · 2016Trial
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- Activated Protein C and the Retina: From Physiology to Therapeutic Potential.International journal of molecular sciences · 2026Review
- Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C.Aging · 2024Article
- Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies.International journal of molecular sciences · 2024Review
- Selective modulation of activated protein C activities by a nonactive site-targeting nanobody library.Blood advances · 2023Article
- Review
- Neuroprotective Strategies for Ischemic Stroke-Future Perspectives.International journal of molecular sciences · 2023Review
- Dysregulated haemostasis in thrombo-inflammatory disease.Clinical science (London, England : 1979) · 2022Review
- The Development of Novel Drug Treatments for Stroke Patients: A Review.International journal of molecular sciences · 2022Review
- Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.The Journal of experimental medicine · 2022Article
- 3K3A-Activated Protein C Protects the Blood-Brain Barrier and Neurons From Accelerated Ischemic Injury Caused by Pericyte Deficiency in Mice.Frontiers in neuroscience · 2022Article
- Article
- The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies.Biomolecules · 2021Review
- Old drug, new Trick? The rationale for the treatment of COVID-19 with activated protein C.Medical hypotheses · 2021Article
- Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies.Experimental neurology · 2021Review
- Article
- COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation.Research and practice in thrombosis and haemostasis · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
background and purposeActivated Protein C (APC) stimulates multiple cytoprotective pathways via the protease activated receptor-1 (PAR-1) and promotes anticoagulation. 3K3A-APC was designed for preserved activity at PAR-1 with reduced anticoagulation. This Phase 1 trial characterized pharmacokinetics and anticoagulation effects of 3K3A-APC.
methodsSubjects (n=64) were randomly assigned to receive 3K3A-APC (n=4) at 6, 30, 90, 180, 360, 540 or 720 µg/kg or placebo (n=6) and were observed for 24 hr. After safety review additional subjects received drug every 12 hr for 5 doses (n=6 per group) at 90, 180, 360, or 540 µg/kg or placebo (n=8) and were observed for 24 hr.
resultsAll subjects returned for safety assessments at 72 hours and 15 days. We found few adverse events in all groups. Systolic blood pressure increased in both active and placebo groups. Moderately severe headache, nausea and vomiting were reported in one of two subjects treated with 720 µg/kg so 540 µg/kg was considered the highest tolerated dose. Mean plasma concentrations increased in proportion to dose. Clearance ranged from 11,693 ± 807 to 18,701 ± 4,797 mL/hr, volume of distribution ranged from 4,873±828 to 6,971 ± 1,169 mL, and elimination half-life ranged from 0.211 ± 0.097 to 0.294 ± 0.054 hours. Elevations in aPTT were minimal.
conclusions3K3A-APC was well tolerated at multiple doses as high as 540 µg/kg. These results should be confirmed in stroke patients with relevant co-morbidities. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660230.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.