ArticleThe AAPS journal2024
Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model.
Article in The AAPS journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 6 registered trials, which are not on this map. Cited by 12 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 Phase 1, Randomized, Double Blind, Third-party Open, Placebo-controlled, Single And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-06651600 In Healthy Subjects
A Phase 1, Open Label, Single-dose 3-way Crossover Study To Evaluate The Relative Bioavailability Of A Solid Dose Formulation Of Pf-06651600 Under Fasting Conditions And The Effect Of A High Fat Meal On The Bioavailability Of The Solid Dosage Formulation Of Pf-06651600 In Healthy Subjects
A phase 1, randomized, open-label, cross-over, single dose study to estimate the relative bioavailability of candidate capsule formulations of pf-06651600 relative to tablets in healthy participants
A phase 1, randomized, open-label, cross-over, single-dose study to evaluate the bioequivalence of candidate capsule formulations of pf-06651600 to tablets and estimate the effect of high-fat meal on bioavailability in healthy participants
A phase 1, randomized, open-label, cross-over, single dose study to estimate the relative bioavailability of pediatric ritlecitinib (pf-06651600) capsules and spray congealed beads relative to adult capsules in healthy adult participants
An open label, phase 1, two-arm study to assess target occupancy and functional inhibition of jak3 and tec kinases by single doses of ritlecitinib in healthy adult participants
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Pyridoxic Acid as Endogenous Biomarker of Renal Organic Anion Transporter Activity: Population Variability and Mechanistic Modeling to Predict Drug-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Is a Clinical Trial With a Non-Bioequivalent Batch Necessary? The Critical Role of Intrasubject Variability in Olaparib Formulation Bridging by PBPK.Clinical pharmacology and therapeutics · 2026Article
- Quantitative Estimation of Clinical Intrasubject Variability of a Pharmacokinetic Parameter.The AAPS journal · 2026Article
- Virtual Bioequivalence Assessment of Long-acting Injectable Suspensions Using PBPK Modeling: Part 1. Impact of particle Size on Formulation Variability.The AAPS journal · 2026Article
- Pharmacological Insights on USFDA-approved Novel Drug Therapies in the Year 2023.Current drug discovery technologies · 2026Review
- An Open-Source Framework for Virtual Bioequivalence Modeling and Clinical Trial Design.CPT: pharmacometrics & systems pharmacology · 2025Article
- Commentary and Review on Prospective Prediction of Bioequivalence of Oral Dosage Forms using Compendial Dissolution Testing and PBPK Modeling.The AAPS journal · 2025Review
- Article
- PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations.Pharmaceutical research · 2025Article
- Virtual Bioequivalence Assessment of Tofacitinib Once Daily Modified Release Dosage Form in Pediatric Subjects.The AAPS journal · 2025Article
- A Semi-Mechanistic Physiologically Based Biopharmaceutics Model to Describe Complex and Saturable Absorption of Metformin: Justification of Dissolution Specifications for Extended Release Formulation.AAPS PharmSciTech · 2024Article
- More Than a Gut Feeling─A Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.Molecular pharmaceutics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ritlecitinib, an orally available Janus kinase 3 and tyrosine kinase inhibitor being developed for the treatment of alopecia areata (AA), is highly soluble across the physiological pH range at the therapeutic dose. As such, it is expected to dissolve rapidly in any in vitro dissolution conditions. However, in vitro dissolution data showed slower dissolution for 100-mg capsules, used for the clinical bioequivalence (BE) study, compared with proposed commercial 50-mg capsules. Hence, a biowaiver for the lower 50-mg strength using comparable multimedia dissolution based on the f2 similarity factor was not possible. The in vivo relevance of this observed in vitro dissolution profile was evaluated with a physiologically based pharmacokinetic (PBPK) model. This report describes the development, verification, and application of the ritlecitinib PBPK model to translate observed in vitro dissolution data to an in vivo PK profile for ritlecitinib capsule formulations. Virtual BE (VBE) trials were conducted using the Simcyp VBE module, including the model-predicted within-subject variability or intra-subject coefficient of variation (ICV). The results showed the predicted ICV was predicted to be smaller than observed clinical ICV, resulting in a more optimistic BE risk assessment. Additional VBE assessment was conducted by incorporating clinically observed ICV. The VBE trial results including clinically observed ICV demonstrated that proposed commercial 50-mg capsules vs clinical 100-mg capsules were bioequivalent, with > 90% probability of success. This study demonstrates a PBPK model-based biowaiver for a clinical BE study while introducing a novel method to integrate clinically observed ICV into VBE trials with PBPK models. Trial registration: NCT02309827, NCT02684760, NCT04004663, NCT04390776, NCT05040295, NCT05128058.
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.