Evidence map›Paper›PMID 28623849›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2017

Population Pharmacokinetics/Pharmacodynamics of 3,4-Diaminopyridine Free Base in Patients With Lambert-Eaton Myasthenia.

Nilay Thakkar, Jeffrey T Guptill, Kathy Aleš, David Jacobus, Laura Jacobus, Charles Peloquin, Michael Cohen-Wolkowiez, Daniel Gonzalez, DAPPER Study Group

Open access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Investigation ofPharmaceutics · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. 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

9 authors at 5 institutions in 1 country.

Nilay ThakkarDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jeffrey T GuptillDuke Clinical Research Institute, Durham, North Carolina, USA.
Kathy AlešJacobus Pharmaceutical Company, Inc., Plainsboro, New Jersey, USA.
David JacobusJacobus Pharmaceutical Company, Inc., Plainsboro, New Jersey, USA.
Laura JacobusJacobus Pharmaceutical Company, Inc., Plainsboro, New Jersey, USA.
Charles PeloquinCollege of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
Michael Cohen-WolkowiezDuke Clinical Research Institute, Durham, North Carolina, USA.
Daniel GonzalezDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
DAPPER Study Group
Clinical Research Institute · USJacobi Medical Center · USUniversity of North Carolina at Chapel Hill · USPrinceton Satellite Systems (United States) · USUniversity of Florida · US

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Duke CTSA (Composite)UL1TR001117 · NCATS · DUKE UNIVERSITY · PI BOULWARE, LEIGH E, LI, JENNIFER S · 2013 to 2017
$41.3M
Immunological biomarker studies in myasthenia gravisK23NS085049 · NINDS · DUKE UNIVERSITY · PI GUPTILL, JEFFREY T · 2014 to 2018
$924k
Use of Physiologically-Based PK/PD Models to Streamline Drug ApprovalsK23HD083465 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GONZALEZ, DANIEL · 2015 to 2019
$727k
Clinical Practice Data to Aid Narrow Therapeutic Index Drug ClassificationU01FD004858 · FDA · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL · 2013 to 2014
$497k
FDA HHS U01 FD004858NCATS NIH HHS UL1 TR001117NCATS NIH HHS UL1 TR002369NIAID NIH HHS HHSN272201300017CNIAID NIH HHS HHSN272201300017INIAID NIH HHS HHSN272201500006CNICHD NIH HHS HHSN275201000003CNICHD NIH HHS HHSN275201000003INICHD NIH HHS K23 HD083465NINDS NIH HHS K23 NS085049
6 · The paper itself

Abstract

Lambert-Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine (3,4-DAP) free base is an investigational orphan drug used to treat LEM-related weakness. We performed a population pharmacokinetic/pharmacodynamic (PK/PD) analysis using 3,4-DAP and metabolite concentrations collected from a phase II study in patients with LEM. The Triple Timed Up & Go (3TUG) assessment, which measures lower extremity weakness, was the primary outcome measure. A total of 1,270 PK samples (49 patients) and 1,091 3TUG data points (32 randomized patients) were included in the PK/PD analysis. A two-compartment and one-compartment model for parent and metabolite, respectively, described the PK data well. Body weight and serum creatinine partially explained the variability in clearance for the final PK model. A fractional inhibitory maximum effect (E

Indexed as

Models, BiologicalPotassium Channel Blockers4-AminopyridineAdultAgedAged, 80 and overAmifampridineArylamine N-AcetyltransferaseFemaleHumansLambert-Eaton Myasthenic SyndromeLower ExtremityMaleMiddle AgedMuscle WeaknessPolymorphism, Single Nucleotide4-AminopyridineAmifampridineArylamine N-AcetyltransferaseNAT2 protein, humanPotassium Channel Blockers

Identifiers

PMID28623849
PMCPMC5613184
OpenAlexW2625389878

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.