ArticleClinical pharmacokinetics2024
Moving Beyond Boundaries: Utilization of Longitudinal Exposure-Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm.
Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Exposure-response modeling of liver fat imaging endpoints in non-alcoholic fatty liver disease populations administered ervogastat alone and co-administered with clesacostat.CPT: pharmacometrics & systems pharmacology · 2025Trial
- 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
- Description of the Tranquillo Phase 3 Clinical Trial Designs/Study Protocols to Assess Ritlecitinib in Adults and Adolescents with Nonsegmental Vitiligo.Dermatology and therapy · 2026Article
- Rationale and Design of a Novel, Phase 3, External and Synthetic Placebo-Controlled Clinical Trial of Ritlecitinib 50 mg and 100 mg for Alopecia Areata.Dermatology and therapy · 2025Article
- Comprehensive Safety Exposure-Response Analysis to Support Ritlecitinib Dose Selection.CPT: pharmacometrics & systems pharmacology · 2025Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesAs drug development scientists strive to accelerate availability of therapies for patients, model-informed drug development (MIDD) plays an important role in contextualizing existing information and facilitating decision making. This paper describes an example of MIDD, where modeling and simulation informed decision making in the circumstance of a combined phase 2b and single pivotal study for ritlecitinib (JAK3/TEC family kinases inhibitor).
methodsLongitudinal exposure-response (ER) modeling was conducted to describe ritlecitinib efficacy in alopecia areata patients. The Severity of Alopecia Tool (SALT) score (a continuous bounded outcome [CBO] score [0-100]) was used as the efficacy response. The average concentration during the time interval between two adjacent SALT scores was used as the exposure metric driving efficacy.
resultsThe developed model well described the longitudinal SALT profile of ritlecitinib as well as the frequency of boundary data. The CBO model indicated tested doses in the phase 2b/3 clinical trial are in the ascending region of ER and contextualized a loading dose effect that impacted onset of efficacy without long-term benefit. It also identified disease severity as the only covariate impacting efficacy. The model-based simulation further informed impact of treatment interruption on the loss of efficacy in the absence of a dedicated treatment withdrawal study. Results indicated temporary treatment interruption ≤ 6 weeks is not expected to result in significant loss of efficacy.
conclusionThe CBO modeling approach and simulation supported the single pivotal trial strategy and guided dose selection in the accelerated drug development program of ritlecitinib, which can be applied to many indications where efficacy is measured on a bounded scale.
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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.