Advertisement

Topics

Exposure-Response Analyses of Upadacitinib Efficacy in Phase 2 Trials in Rheumatoid Arthritis and Basis for Phase 3 Dose Selection.

08:00 EDT 13th June 2019 | BioPortfolio

Summary of "Exposure-Response Analyses of Upadacitinib Efficacy in Phase 2 Trials in Rheumatoid Arthritis and Basis for Phase 3 Dose Selection."

The relationships between upadacitinib, an oral selective Janus Kinase 1 inhibitor, plasma exposures and its efficacy (assessed by ACR20/50/70 responses over time) in moderate-to severe active rheumatoid arthritis (RA) were characterized using data from 574 patients, on background methotrexate and inadequate response to methotrexate or anti-TNF therapy, from two Phase 2 trials conducted with twice-daily dosing of an immediate-release formulation. The developed time-continuous Markov models were used to simulate efficacy of QD regimens of upadacitinib extended-release incorporating sources of uncertainty. Upadacitinib plasma concentrations associated with 15 and 30 mg extended-release QD doses were predicted to achieve that plateau of response across RA subpopulations. Results from these analyses provided the rationale that supported selection, and de-risked evaluation, of upadacitinib extended-release doses for the first time in more than 4000 patients in five large Phase 3 trials. This article is protected by copyright. All rights reserved.

Affiliation

Journal Details

This article was published in the following journal.

Name: Clinical pharmacology and therapeutics
ISSN: 1532-6535
Pages:

Links

DeepDyve research library

PubMed Articles [30109 Associated PubMed Articles listed on BioPortfolio]

Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials.

The relative efficacy and safety of tofacitinib and upadacitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic (cs) or biologic (b) dis...

Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics.

Upadacitinib is a novel selective Janus kinase 1 inhibitor developed for treatment of rheumatoid arthritis and other autoimmune diseases. The objective of this study was to assess the pharmacokinetics...

Characterization of the Effect of Hepatic Impairment on Upadacitinib Pharmacokinetics.

Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis. Upadacitinib is a nonsensitive subst...

The JAK1 Inhibitor Upadacitinib Has No Effect on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol: A Study in Healthy Female Subjects.

Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being developed for treatment of several inflammatory diseases. Oral contraceptives are anticipated to be a common concomitant med...

Reduced IgG titers against pertussis in rheumatoid arthritis: Evidence for a citrulline-biased immune response and medication effects.

The antibody response to pertussis vaccination in rheumatoid arthritis is unknown, a concerning omission given the relatively low efficacy of the pertussis vaccine, a rise in pertussis infections, and...

Clinical Trials [14737 Associated Clinical Trials listed on BioPortfolio]

A Study in Rheumatoid Arthritis Patients Who Have Completed a Preceding Study With ABBV-105 Given Alone or in Combination With Upadacitinib

This is a long-term extension (LTE) study to assess the safety, tolerability abd efficacy of ABBV-105 and ABBV-599 in Rheumatoid Arthritis (RA) participants who have completed M16-063.

A Study to Investigate the Safety and Efficacy of ABBV-105 Alone or in Combination With Upadacitinib (ABBV-599 Combination) in Participants With Active Rheumatoid Arthritis.

This is a phase 2 study to evaluate safety and efficacy of ABBV-105 and ABBV-599 (ABBV-105 plus upadacitinib) vs placebo on a background of conventional synthetic disease-modifying anti-rh...

A Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis

The objective of this study is to assess the efficacy and safety of upadacitinib for the treatment of adolescent and adult participants with moderate to severe AD who are candidates for sy...

A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Crohn's Disease Who Completed the Studies M14-431 or M14-433

A multicenter study to evaluate the efficacy and safety of maintenance and long-term treatment administration of upadacitinib, an orally administered Janus kinase 1 inhibitor, in adult par...

A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Conventional Therapies But Have Not Failed Biologic Therapy

The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and severely active Crohn's dise...

Medical and Biotech [MESH] Definitions

Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.

Planned post-marketing studies of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques that have been approved for general sale. These studies are often conducted to obtain additional data about the safety and efficacy of a product. This concept includes phase IV studies conducted in both the U.S. and in other countries.

Comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.

Work that is a report of a planned post-marketing study of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques that have been approved for general sale after clinical trials, phases I, II, and III. These studies, conducted in the United States or a foreign country, often garner additional data about the safety and efficacy of a product.

Pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Orthopedics
Arthroplasty Joint Disorders Orthopedics Spinal Cord Disorders Orthopedics is the science or practice of correcting deformities caused by disease or damage to the bones and joints of the skeleton. This specialized branch of surgery may ...


Searches Linking to this Article