Evidence map›Paper›PMID 29671202›Full record

Trial reportClinical pharmacokinetics2019

Pharmacokinetics and Pharmacodynamics of Once-Weekly Somapacitan in Children and Adults: Supporting Dosing Rationales with a Model-Based Analysis of Three Phase I Trials.

Rasmus Vestergaard Juul, Michael Højby Rasmussen, Henrik Agersø, Rune Viig Overgaard

3 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC 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 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 12% 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.

NCT01514500 phase1completednot on this map

First Human Dose Trial of NNC0195-0092 (Somapacitan) in Healthy Subjects

TypeinterventionalSponsorNovo Nordisk A/SRan2012 to 2013Enrolled105ConditionsGrowth Hormone Disorder, Adult Growth Hormone Deficiency, Growth Hormone Deficiency in Children, HealthyArmssomapacitan, placebo (somapacitan)
NCT01706783 phase1completednot on this map

A Randomised, Open-labelled, Active-controlled, Multiple Dose, Dose Escalating, Sequential Dose Group Trial Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once-weekly Long-acting Growth Hormone (NNC0195-0092, Somapacitan) Compared to Once-daily Norditropin NordiFlex® in Adults With Growth Hormone Deficiency

TypeinterventionalSponsorNovo Nordisk A/SRan2012 to 2013Enrolled35ConditionsGrowth Hormone Disorder, Adult Growth Hormone DeficiencyArmssomapacitan, Norditropin NordiFlex®
NCT01973244 phase1completednot on this map

A Randomised, Open-labelled, Active-controlled, Multinational, Dose-escalation Trial Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of Long-acting Growth Hormone (NNC0195-0092, Somapacitan) Compared to Daily Dosing of Norditropin® SimpleXx® in Children With Growth Hormone Deficiency

TypeinterventionalSponsorNovo Nordisk A/SRan2013 to 2014Enrolled32ConditionsGrowth Hormone Disorder, Growth Hormone Deficiency in ChildrenArmssomapacitan, somatropin
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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  16. Long-Lasting Growth Hormone Regulated by the Ubiquitin-Proteasome System.International journal of molecular sciences · 2021
    Article
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  19. Long-Acting Growth Hormone Preparations - Current Status and Future Considerations.The Journal of clinical endocrinology and metabolism · 2020
    Review
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 at 1 institution in 1 country.

Rasmus Vestergaard JuulGlobal Development, Novo Nordisk A/S, Bagsvaerd, Denmark. rvej@novonordisk.com.
Michael Højby RasmussenGlobal Development, Novo Nordisk A/S, Bagsvaerd, Denmark.
Henrik AgersøGlobal Development, Novo Nordisk A/S, Bagsvaerd, Denmark.
Rune Viig OvergaardGlobal Development, Novo Nordisk A/S, Bagsvaerd, Denmark.
Novo Nordisk (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSomapacitan, a long-acting growth hormone (GH) derivative, has been well-tolerated in children with GH deficiency (GHD) and adults (healthy and adult GHD), in phase I, single- and multiple-dose trials, respectively, and has pharmacokinetic and pharmacodynamic properties supporting a once-weekly dosing regimen.

objectiveIn the absence of a multiple-dose phase I trial in children with GHD, the aim was to develop a pharmacokinetic/pharmacodynamic model to predict somapacitan exposure and insulin-like growth factor-I (IGF-I) response after once-weekly multiple doses in both children and adults with GHD.

methodsPharmacokinetic/pharmacodynamic models were developed from pharmacokinetic and IGF-I profiles in three phase I trials of somapacitan (doses: healthy adults, 0.01-0.32 mg/kg; adult with GHD, 0.02-0.12 mg/kg; children with GHD, 0.02-0.16 mg/kg) using non-linear mixed-effects modeling. Pharmacokinetics were described using a non-linear one-compartment model with dual first- and zero-order absorption through a transit compartment, with saturable elimination. IGF-I profiles were described using an indirect response pharmacokinetic/pharmacodynamic model, with sigmoidal-effect relationship.

resultsThe non-linear pharmacokinetic and IGF-I data were well-described in order to confidently predict pharmacokinetic/pharmacodynamic profiles after multiple doses in adults and children with GHD. Body weight was found to be a significant covariate, predictive of the differences observed in the pharmacokinetics and pharmacodynamics between children and adults. Weekly dosing of somapacitan provided elevated IGF-I levels throughout the week, despite little or no accumulation of somapacitan, in both adults and children with GHD.

conclusionThis analysis of somapacitan pharmacokinetic/pharmacodynamic data supports once-weekly dosing in adults and children with GHD.

trial registrationClinicalTrials.gov identifier numbers NCT01514500, NCT01706783, NCT01973244.

Indexed as

Growth HormoneModels, BiologicalAdultAgedBody WeightChildDrug Administration ScheduleDwarfism, PituitaryFemaleHumansInsulin-Like Growth Factor IMaleMiddle AgedYoung AdultGrowth HormoneIGF1 protein, humanInsulin-Like Growth Factor I

Identifiers

PMID29671202
PMCPMC6325982
OpenAlexW2799484096

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.