ArticleClinical pharmacokinetics2023
Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 12 registered trials, which are not on this map. Cited by 9 papers.
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 2b, double-blind, randomized, placebo-controlled, parallel group, dose ranging study of oral pf-06651600 and pf-06700841 as induction and chronic therapy in subjects with moderate to severe ulcerative colitis
A Phase 2a, Randomized, Double-blind, Parallel Group, Placebo-controlled, Multi-center Study To Assess The Efficacy And Safety Profile Of Pf-06651600 In Subjects With Moderate To Severe Active Rheumatoid Arthritis With An Inadequate Response To Methotrexate
A phase 2a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety profile of pf-06651600 and pf-06700841 in subjects with moderate to severe alopecia areata with a single-blind extension period and a cross-over open label extension period
A Phase 1, Randomized, Double-blind, Third-party Open, Placebo-controlled Study To Evaluate The Safety, Tolerability, And Pharmacokinetics After Multiple Oral Doses Of Pf-06651600 In Healthy Japanese Subjects
A phase 2b randomized, double-blind, placebo-controlled, multicenter, dose-ranging study to evaluate the efficacy and safety profile of pf-06651600 with a partially blinded extension period to evaluate the efficacy and safety of pf-06651600 and pf-06700841 in subjects with active non-segmental vitiligo
A phase 2b/3 randomized, double-blind, placebo-controlled, dose-ranging study to investigate the efficacy and safety of pf-06651600 in adult and adolescent alopecia areata (aa) subjects with 50% or greater scalp hair loss
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, non-randomized, open label, multiple dose study to evaluate the pharmacokinetics, safety and tolerability of pf 06651600 in subjects with hepatic impairment and in healthy subjects with normal hepatic function
A phase 1, non-randomized, open label, multiple dose study to evaluate the pharmacokinetics, safety and tolerability of pf 06651600 in participants with renal impairment and in healthy participants with normal renal function
A single center, open label, single arm study to investigate the repeated dose (for 10 days) pharmacokinetics after oral administration of 200 mg pf-06651600 in chinese healthy adult participants
Who cites it
9 citing papers in PubMed.
- Population exposure-response analysis of the effect of ritlecitinib on eyebrow assessment and eyelash assessment in patients with alopecia areata.CPT: pharmacometrics & systems pharmacology · 2025Trial
- A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.Pharmacology research & perspectives · 2024Trial
- MIDD Evidence to Support Drug Regulatory Decisions in China.Clinical and translational science · 2026Review
- Drug-drug interaction profile of ritlecitinib as perpetrator and victim through cytochrome P450.British journal of clinical pharmacology · 2025Article
- Comprehensive Safety Exposure-Response Analysis to Support Ritlecitinib Dose Selection.CPT: pharmacometrics & systems pharmacology · 2025Article
- Operating Characteristics of the Simulated Healthy Participant Approach in Impaired Clearance Studies.The AAPS journal · 2025Article
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- Moving Beyond Boundaries: Utilization of Longitudinal Exposure-Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm.Clinical pharmacokinetics · 2024Article
- A Phase 1, Open-Label Study of the Pharmacokinetics of Ritlecitinib in Children Aged 6-12 Years With Alopecia Areata.Pediatric dermatologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRitlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor undergoing parallel clinical development for alopecia areata, vitiligo, ulcerative colitis, Crohn's disease, and rheumatoid arthritis.
objectiveAs studies read out simultaneously, strategic planning of population pharmacokinetic model development and evaluation is required to ensure timely decisions.
methodsData from healthy participants and patients from 12 clinical trials between December 2014 and July 2021 were included: seven phase I studies in healthy participants and organ impairment, five phase II/III studies in patients with rheumatoid arthritis, ulcerative colitis, alopecia areata, and vitiligo. Population pharmacokinetic models consisted of stepwise procedures to accommodate data availability and the model's application to answering clinical development questions. At each iteration of the model update, parameters of the next model were re-estimated by leveraging previous information and new data.
resultsThree model development lifecycle iterations of the ritlecitinib population pharmacokinetic model were conducted to support alopecia areata, vitiligo, and ulcerative colitis study readouts. Initial structural modeling based on healthy participant data (and some rheumatoid arthritis and alopecia areata data) in iteration 1 provided a platform for comprehensive covariate testing during iteration 2, and model evaluation and implementation of the frequentist prior approach in iteration 3. The final model was a two-compartment model with first-order absorption and direct-response non-stationary clearance and bioavailability driven by concentrations in the peripheral compartment.
conclusionsThe present approach demonstrated the evolution of three population pharmacokinetic models with accumulating data, addressed clinical drug development questions related to systemic exposures of ritlecitinib, and informed the approved product label. CLINICAL
trial registrationNCT02309827, NCT02684760, NCT02958865, NCT02969044, NCT03232905, NCT03732807, NCT04016077, NCT03715829, NCT04037865, NCT04004663, NCT04634565, NCT02974868.
Indexed as
Identifiers
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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.