Evidence mapPaperPMID 20002082Full record

Trial reportBritish journal of clinical pharmacology2009

Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers.

Kyoung Soo Lim, Joo-Youn Cho, Bo-Hyung Kim, Jung-Ryul Kim, Hwa-Sook Kim, Dong-Kyu Kim, Sung-Ho Kim, Hyeon Joo Yim, Sung-Hack Lee, Sang-Goo Shin and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03310749 (A Randomized, Open-label, Multiple Dosing, Three-way Crossover Clinical Trial to Investigate the Pharmacokinetic Drug-drug Interaction of Gemigliptin and Metformin After Oral Administration in Healthy Mexican Male Subjects), which is not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
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.

NCT03310749 phase1completedstarted 2016, after this paper: background citation

A Randomized, Open-label, Multiple Dosing, Three-way Crossover Clinical Trial to Investigate the Pharmacokinetic Drug-drug Interaction of Gemigliptin and Metformin After Oral Administration in Healthy Mexican Male Subjects

Ran2016Enrolled34Registered outcomes11Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsGemigliptin, Gemigliptin 50 mg q.d. + metformin 1000 mg twice a day, Metformin
Open the trial in the graph
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Synthesis, X-ray diffraction analysis, quantum chemical studies andJournal of enzyme inhibition and medicinal chemistry · 2022
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Gemigliptin: Newer Promising Gliptin for Type 2 Diabetes Mellitus.Indian journal of endocrinology and metabolism
    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

12 authors.

Kyoung Soo LimDepartment of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Joo-Youn Cho
Bo-Hyung Kim
Jung-Ryul Kim
Hwa-Sook Kim
Dong-Kyu Kim
Sung-Ho Kim
Hyeon Joo Yim
Sung-Hack Lee
Sang-Goo Shin
In-Jin Jang
Kyung-Sang Yu

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

what is already known about this subject* The importance of efficient drug development using biomarkers has been increasingly emphasized, from preclinical studies to clinical trials. * However, as yet few validated or qualified biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology. WHAT THIS STUDY ADDS: * This first-time-in-human study provides evidence of the pharmacological activity of LC15-0444 in humans, by using dipeptidyl peptidase IV activity and active glucagon-like peptide-1 concentrations. * LC15-0444 possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen.

aimsLC15-0444 is a selective and competitive inhibitor of dipeptidyl peptidase (DPP) IV with potential for the treatment of Type 2 diabetes. The aim was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles after multiple oral ascending doses of LC15-0444 in healthy male subjects.

methodsA dose block-randomized, double-blind, placebo-controlled, parallel group study was performed in three groups with 10 subjects (eight for active drug; two for placebo) per group; each group received 200, 400 or 600 mg of LC15-0444 once daily for 10 days. Blood and urine samples were collected up to 24 h after the first dosing and up to 72 h after the last dosing.

resultsThe LC15-0444 concentration-time profiles exhibited characteristics of multicompartment disposition. No dose- or time-dependent change in PK parameters was observed. Mean elimination half-life was in a range 16.6-20.1 h in the dose groups. Mean renal clearance and fraction of unchanged drug excreted in urine was 18.6-21.9 and 0.40-0.48 l h(-1), respectively. In the steady state, mean accumulation ratios by dose groups were between 1.22 and 1.31. More than 80% inhibition of DPP IV activity from baseline was sustained for >24 h in all dose groups.

conclusionsThis study provides evidence of the pharmacological activity of LC15-0444 in humans. LC15-0444 possesses PK and PD characteristics that support a once-daily dosing regimen.

Indexed as

Administration, OralAdultArea Under CurveDipeptidyl-Peptidase IV InhibitorsDose-Response Relationship, DrugDouble-Blind MethodHumansKoreaMaleMetabolic Clearance RateOrganic ChemicalsPiperidonesPyrimidinesYoung AdultDipeptidyl-Peptidase IV InhibitorsLC15-0444Organic ChemicalsPiperidonesPyrimidines

Identifiers

PMID20002082
PMCPMC2810799

What Socratic holds

Textmetadata
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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 Socratic graph.