Trial reportBritish journal of clinical pharmacology2014
Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases.
Trial report in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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.
Who cites it
15 citing papers in PubMed.
- Development of New Molecularly Targeted Agents in Inflammatory Bowel Disease.Internal medicine (Tokyo, Japan) · 2026Review
- [Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Emerging Therapies for Ulcerative Colitis: Updates from Recent Clinical Trials.Clinical and experimental gastroenterology · 2023Review
- Emerging therapeutic options in inflammatory bowel disease.World journal of gastroenterology · 2021Review
- Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.Clinical and experimental gastroenterology · 2021Review
- Subcutaneous integrin inhibitors may provide more treatment options for patients with moderate-to-severe ulcerative colitis.Intestinal research · 2019Article
- Emerging Therapies for Inflammatory Bowel Disease.Advances in therapy · 2018Review
- Frontiers in Drug Research and Development for Inflammatory Bowel Disease.Frontiers in pharmacology · 2017Review
- Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development.Cytometry. Part B, Clinical cytometry · 2016Review
- Integrin-based therapeutics: biological basis, clinical use and new drugs.Nature reviews. Drug discovery · 2016Review
- Integrin antagonists as potential therapeutic options for the treatment of Crohn's disease.Expert opinion on investigational drugs · 2016Review
- Current stage in inflammatory bowel disease: What is next?World journal of gastroenterology · 2015Review
- Emerging Treatment Options in Mild to Moderate Ulcerative Colitis.Gastroenterology & hepatology · 2015Article
- Prediction of clinical pharmacokinetics of AMG 181, a human anti-α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases.Pharmacology research & perspectives · 2015Article
- Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab.Drug design, development and therapy · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAMG 181 pharmacokinetics/pharmacodynamics (PK/PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double-blind, placebo-controlled study.
methodsHealthy male subjects (n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis (UC) subjects (n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti-AMG 181-antibody (ADA), α4 β7 receptor occupancy (RO), target cell counts, serum C-reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3-9 months after dose.
resultsFollowing s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2-10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose-proportionally and approximately dose-proportionally, respectively, within the 70-210 mg s.c. and 70-420 mg i.v. ranges. The linear β-phase t1/2 was 31 (range 20-48) days. Target-mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml(-1) . The PD effect on α4 β7 RO showed an EC50 of 0.01 μg ml(-1) . Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181-treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo-treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment-related serious adverse events were observed.
conclusionsAMG 181 has PK/PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases.
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