Evidence map›Paper›PMID 30915660›Full record

Trial reportClinical pharmacokinetics2019

Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis.

Petra Jauslin, Pooja Kulkarni, Hanbin Li, Suresh Vatakuti, Azher Hussain, Larissa Wenning, Thomas Kerbusch

3 registry-linked trialsAbstract readClinical Trial, Phase IClinical Trial, Phase IIClinical Trial, Phase III
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT01225731 phase2completednot on this map

Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding Study of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Study P05495)

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2010 to 2012Enrolled355ConditionsPsoriasisArmstildrakizumab, Placebo
NCT01722331 phase3completednot on this map

A 64-Week, Phase 3, Randomized, Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-010)

TypeinterventionalSponsorSun Pharmaceutical Industries LimitedRan2012 to 2021Enrolled772ConditionsPlaque PsoriasisArmsTildrakizumab 200 mg, Tildrakizumab 100 mg, Matching Placebo
NCT01729754 phase3completednot on this map

A 52-Week, Phase 3, Randomized, Active Comparator and Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-011)

TypeinterventionalSponsorSun Pharmaceutical Industries LimitedRan2013 to 2021Enrolled1,090ConditionsPlaque PsoriasisArmsTildrakizumab 200 mg, Tildrakizumab 100 mg, Tildrakizumab Placebo, Etanercept Placebo, Etanercept 50 mg
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
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  4. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Petra JauslinCertara USA, Inc., Princeton, NJ, USA.
Pooja KulkarniCertara USA, Inc., Princeton, NJ, USA.
Hanbin LiCertara USA, Inc., Princeton, NJ, USA.
Suresh VatakutiCertara USA, Inc., Princeton, NJ, USA.
Azher HussainMerck & Co., Inc., Kenilworth, USA.
Larissa WenningMerck & Co., Inc., Kenilworth, USA. larissa_wenning@merck.com.
Thomas KerbuschCertara USA, Inc., Princeton, NJ, USA.
Integra LifeSciences (United States) · USCertara (United States) · USMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis.

methodsThis analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subjects with psoriasis. Tested covariates included body weight, formulation type, sex, age, race, serum albumin, creatinine clearance, Japanese origin, prior treatment with a biologic agent, subject status (subjects with psoriasis vs. healthy volunteers), and ethnicity.

resultsThe pharmacokinetics was described by a one-compartment model with first-order absorption and elimination kinetics, and inter-individual variability on clearance, volume of distribution, and absorption rate constant. The pharmacokinetics was characterized by low clearance and limited volume of distribution. In subjects with psoriasis, the geometric mean clearance (coefficient of variation) was 0.32 L/day (38%), volume of distribution was 10.8 L (24%), and absorption and elimination half-life were 1.5 days (18%) and 23.4 days (23%), respectively, with an absorption lag time of 1.2 h. For the 100-mg dose, steady-state area under the plasma concentration vs. time curve for one dosing interval and maximum plasma concentration were 305 µg*day/mL (41%) and 8.1 µg/mL (34%), respectively. Steady state was achieved by 16 weeks with the clinical regimen (dosing on week 0 and week 4 and every 12 weeks thereafter) with 1.1-fold accumulation in maximum plasma concentration. Healthy subjects had 31% higher bioavailability than subjects with psoriasis. Subjects with increased body weight had a lower area under the plasma concentration-time curve at steady state vs. those with lower body weight. The modeled exposures were contained within clinical comparability bounds for all covariates including body weight.

conclusionsThe pharmacokinetics of tildrakizumab behaves like a typical monoclonal antibody without requiring dosage adjustment.

trial registrationNCT01729754, NCT01225731, NCT01722331.

Indexed as

AdultAntibodies, Monoclonal, HumanizedBiological AvailabilityBiological Variation, PopulationBody WeightCase-Control StudiesChronic DiseaseCreatinineFemaleHumansInjections, SubcutaneousInterleukin-23MaleMiddle AgedPsoriasisSerum AlbuminAntibodies, Monoclonal, HumanizedCreatinineInterleukin-23Serum Albumintildrakizumab

Identifiers

PMID30915660
OpenAlexW2924461089

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.