Evidence map›Paper›PMID 31550073›Full record

Trial reportClinical and translational science2020

Comparing Model Performance in Characterizing the PK/PD of the Anti-Myostatin Antibody Domagrozumab.

Abhinav Tiwari, Indranil Bhattacharya, Phylinda L S Chan, Lutz Harnisch

Abstract readClinical Trial, Phase IComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Clinical and translational science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  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

4 authors.

Abhinav TiwariDepartment of Clinical Pharmacology, Pfizer, Cambridge, Massachusetts, USA.
Indranil BhattacharyaQuantitative Clinical Pharmacology, Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA.ORCID 0000-0001-9268-6844
Phylinda L S ChanDepartment of Clinical Pharmacology/Pharmacometrics, Pfizer, Sandwich, Kent, UK.
Lutz HarnischDepartment of Clinical Pharmacology/Pharmacometrics, Pfizer, Sandwich, Kent, UK.ORCID 0000-0002-4085-1577

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Modeling and simulation provides quantitative information on target coverage for dose selection. Optimal model selection often relies on fit criteria and is not necessarily mechanistically driven. One such case is discussed where healthy volunteer data of an anti-myostatin monoclonal antibody domagrozumab were used to develop different target-mediated drug disposition models; a quasi-steady state (QSS) rapid binding approximation model, a Michaelis-Menten (MM)-binding kinetics (MM-BK) model, and an MM-indirect response (MM-IDR) model. Whereas the MM-BK model was identified as optimal in fitting the data, with all parameters estimated with high precision, the QSS model also converged but was not able to capture the nonlinear decline. Although the least mechanistic model, MM-IDR, had the lowest objective function value, the MM-BK model was further developed as it provided a reasonable fit and allowed simulations regarding growth differentiation factor-8 target coverage for phase II dose selection with sufficient certainty to allow for testing of the underlying mechanistic assumptions.

Indexed as

Models, BiologicalAdultAntibodies, Monoclonal, HumanizedClinical Trials, Phase II as TopicComputer SimulationDose-Response Relationship, DrugDrug Administration ScheduleFemaleHealthy VolunteersHumansInfusions, IntravenousInhibitory Concentration 50MaleMyostatinAntibodies, Monoclonal, HumanizeddomagrozumabMSTN protein, humanMyostatin

Identifiers

PMID31550073
PMCPMC6951913

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Registered trials

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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.