Evidence map›Paper›PMID 32068354›Full record

Trial reportClinical pharmacology in drug development2020

Modeling and Simulation of the Pharmacokinetics and Target Engagement of an Antagonist Monoclonal Antibody to Interferon-γ-Induced Protein 10, BMS-986184, in Healthy Participants to Guide Therapeutic Dosing.

Weiguo Cai, Tarek A Leil, Leonid Gibiansky, Murli Krishna, Hongwei Zhang, Huidong Gu, Huadong Sun, John Throup, Subhashis Banerjee, Ihab Girgis

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical pharmacology in drug development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02864264 (Double-Blind, Randomized, Placebo-Controlled, Single Ascending and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Target Engagement of BMS-986184 in Healthy Subjects and to Evaluate the Safety, Efficacy, Pharmacokinetics, Target Engagement, and Pharmacodynamics of BMS-986184 in Patients With Moderate to Severe Ulcerative Colitis), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 38% 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.

NCT02864264 phase1terminatednot on this map

Double-Blind, Randomized, Placebo-Controlled, Single Ascending and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Target Engagement of BMS-986184 in Healthy Subjects and to Evaluate the Safety, Efficacy, Pharmacokinetics, Target Engagement, and Pharmacodynamics of BMS-986184 in Patients With Moderate to Severe Ulcerative Colitis

TypeinterventionalSponsorBristol-Myers SquibbRan2016 to 2017Enrolled7ConditionsHealthy Volunteers, Ulcerative ColitisArmsBMS-986184, Placebo matching BMS-986184
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

10 authors at 1 institution in 1 country.

Weiguo CaiBristol-Myers Squibb, Princeton, New Jersey, USA.
Tarek A LeilBristol-Myers Squibb, Princeton, New Jersey, USA.
Leonid GibianskyQuantPharm LLC, North Potomac, Maryland, USA.
Murli KrishnaBristol-Myers Squibb, Princeton, New Jersey, USA.
Hongwei ZhangBristol-Myers Squibb, Princeton, New Jersey, USA.
Huidong GuBristol-Myers Squibb, Princeton, New Jersey, USA.
Huadong SunBristol-Myers Squibb, Princeton, New Jersey, USA.
John ThroupBristol-Myers Squibb, Princeton, New Jersey, USA.
Subhashis BanerjeeBristol-Myers Squibb, Princeton, New Jersey, USA.
Ihab GirgisBristol-Myers Squibb, Princeton, New Jersey, USA.
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BMS-986184 is a human, second-generation, anti-interferon-γ-induced protein 10 (IP-10) monoclonal antibody. In this study the pharmacokinetics and target engagement (TE) of BMS-986184 in healthy participants were characterized using population-based target-mediated drug disposition (TMDD) modeling and data from a first-in-human study (NCT02864264). The results of the first-in-human study and the model generated were used to conduct stochastic simulations of a virtual population of healthy participants to predict pharmacokinetic exposures and TE responses for different dosage regimens. A 2-compartment, 2-target, TMDD structural model, assuming quasi-steady-state and stimulated production on treatment, was developed by simultaneous fitting of the total drug, serum-free IP-10, and serum total IP-10 concentration data, with the second unobservable target contribution to drug elimination described by the Michaelis-Menten elimination term. Model evaluation confirmed agreement between model predictions and observed data. Simulation of a virtual population of healthy individuals demonstrated that steady state was reached at the eighth dosing interval, and that around 150 mg subcutaneously every other week could be a suitable target dosage regimen for future clinical trials. Integrated modeling strategies such as this can be used to help guide rational clinical trial development of drugs with TMDD, leading to improved dose selection and greater patient benefits.

Indexed as

Antibodies, MonoclonalChemokine CXCL10Models, BiologicalAdolescentAdultComputer SimulationDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansInjections, SubcutaneousMaleMiddle AgedYoung AdultAntibodies, MonoclonalChemokine CXCL10CXCL10 protein, humanIP-10monoclonal antibodypharmacokineticssimulationtarget-mediated drug disposition

Identifiers

PMID32068354
PMCPMC7496395
OpenAlexW3007693863

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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.