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Record W3199499776 · doi:10.1016/j.ocarto.2021.100213

Safety and pharmacokinetics of EP-104IAR (sustained-release fluticasone propionate) in knee osteoarthritis: A randomized, double-blind, placebo-controlled phase 1 trial

2021· article· en· W3199499776 on OpenAlex
Amanda Malone, James J. Price, Nicola Price, Vik Peck, Alan Getgood, Robert J. Petrella, James Helliwell

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
aboutThe title or abstract carries a Canadian signal from the geographic lexicon.

Bibliographic record

VenueOsteoarthritis and Cartilage Open · 2021
Typearticle
Languageen
FieldMedicine
TopicOsteoarthritis Treatment and Mechanisms
Canadian institutionsUniversity of British ColumbiaFowler Kennedy Sport Medicine ClinicWestern UniversityAurinia (Canada)
Fundersnot available
KeywordsMedicinePlaceboOsteoarthritisFluticasone propionatePharmacokineticsRandomized controlled trialAdverse effectInternal medicineAnesthesiaClinical trialPlacebo-controlled studyCorticosteroidDouble blind

Abstract

fetched live from OpenAlex

Objective: EP-104IAR is a novel, sustained-release, intra-articular (IA) formulation of the corticosteroid fluticasone propionate (FP), in development for the treatment of osteoarthritis (OA) pain. This study evaluated the safety, pharmacokinetics (PK) and efficacy of a single dose of EP-104IAR in patients with OA of the knee. Design: This was a multi-center, randomized, double-blind, placebo-controlled trial performed at 3 sites in Canada. Subjects with moderate to severe pain received either a single dose of the investigational product EP-104IAR (15 ​mg) or placebo (vehicle) and were evaluated for up to 42 weeks. The primary outcome measures were safety and PK. The study was not powered to assess efficacy, however patient reported outcome measures were analyzed to evaluate pain and symptom relief. Results: Thirty-two subjects were randomized (21 women, 11 men, mean age: 64.8 years). EP-104IAR was well tolerated. Average serum cortisol levels showed no clinically significant deviations compared to placebo and remained within the normal range of cortisol variation. Plasma PK concentrations were within acceptable safety margins, compared to marketed FP products. Synovial fluid FP levels were approximately 2 orders of magnitude higher and at efficacious concentrations for most subjects. Efficacy evaluations indicated that EP-104IAR provided an immediate improvement of OA symptoms and these effects persisted for 8-12 weeks consistently across all measures. Conclusions: This study provides evidence that 15 ​mg of EP-104IAR is well tolerated and has the potential for efficacy in OA patients. These data support further examination of EP-104IAR in larger clinical studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.136
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.299
Teacher spread0.281 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it