PMID- 27354118 OWN - NLM STAT- MEDLINE DCOM- 20171030 LR - 20220321 IS - 1522-9629 (Electronic) IS - 1094-5539 (Linking) VI - 39 DP - 2016 Aug TI - The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma. PG - 54-63 LID - S1094-5539(16)30044-X [pii] LID - 10.1016/j.pupt.2016.06.005 [doi] AB - BACKGROUND: There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies. The aim of this study was to collect efficacy and safety data for QAW039, an oral chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist, for the treatment of asthma. METHODS: This was an exploratory phase II, double-blind, randomized, placebo-controlled multi-center study. Patients with mild-to-moderate uncontrolled allergic asthma (N = 170) were either without or weaned off inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) and randomized (1:1) to QAW039 (500 mg once daily) or to placebo for 28 days. RESULTS: Overall, 157 patients completed the study. There were no significant differences between QAW039 and placebo for trough forced expiratory volume in 1 s (FEV1) or Asthma control questionnaire (ACQ) in the total population. Subgroup analyses demonstrated that patients with a FEV1 <70% of predicted at baseline treated with QAW039 had significant improvement compared with placebo in trough FEV1 (QAW039- Placebo [Delta] = 207 mL; 90% confidence interval [CI]: 96, 319; P = 0.002) and ACQ7 (Delta = -0.41; 90%CI: -0.69, -0.13; P = 0.009). QAW039 reached a mean maximum concentration (Cmax) of 3440 ng/mL on day 28 at a median Tmax of 1 h (range 0.5-4 h). Most adverse events (AEs) were mild/moderate and balanced between both groups, with no serious AEs. CONCLUSIONS: In the general study population, no improvement in lung function was observed with QAW039. However, a subgroup analysis revealed that patients with greater severity of airflow limitation (FEV1 < 70%) had improved lung function and asthma control when treated with QAW039. QAW039 also demonstrated a favorable safety profile. TRIALS REGISTRATION: ClinicalTrials.govNCT01253603. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Erpenbeck, Veit J AU - Erpenbeck VJ AD - Novartis Pharma AG, Basel, Switzerland. Electronic address: veit.erpenbeck@novartis.com. FAU - Popov, Todor A AU - Popov TA AD - Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria. Electronic address: ted.popov@gmail.com. FAU - Miller, David AU - Miller D AD - NEMRA, North Dartmouth, MA, United States. Electronic address: dmiller@nemra-us.com. FAU - Weinstein, Steven F AU - Weinstein SF AD - Allergy & Immunology, Allergy and Asthma Specialists Medical Group and Research Center, CA, United States. Electronic address: sfw@ocallergy.com. FAU - Spector, Sheldon AU - Spector S AD - Allergy & Asthma, California Allergy and Asthma Medical Group Inc, CA, United States. Electronic address: calallergy@gmail.com. FAU - Magnusson, Baldur AU - Magnusson B AD - Novartis Pharma AG, Basel, Switzerland. Electronic address: baldur.magnusson@novartis.com. FAU - Osuntokun, Wande AU - Osuntokun W AD - Novartis Pharmaceuticals, Horsham, United Kingdom. Electronic address: wande.osuntokun@takeda.com. FAU - Goldsmith, Paul AU - Goldsmith P AD - Novartis Pharmaceuticals, Horsham, United Kingdom. Electronic address: pgoldsmith0@gmail.com. FAU - Weiss, Markus AU - Weiss M AD - Novartis Pharma AG, Basel, Switzerland. Electronic address: markus.weiss@novartis.com. FAU - Beier, Jutta AU - Beier J AD - INSAF, Respiratory Research Institute GmbH, Wiesbaden, Germany. Electronic address: j.beier@insaf-wi.de. LA - eng SI - ClinicalTrials.gov/NCT01253603 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20160621 PL - England TA - Pulm Pharmacol Ther JT - Pulmonary pharmacology & therapeutics JID - 9715279 RN - 0 (Anti-Asthmatic Agents) RN - 0 (Indoleacetic Acids) RN - 0 (Pyridines) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Prostaglandin) RN - 2PEX5N7DQ4 (fevipiprant) RN - XZF106QU24 (prostaglandin D2 receptor) SB - IM MH - Administration, Oral MH - Adult MH - Anti-Asthmatic Agents/adverse effects/pharmacokinetics/*therapeutic use MH - Asthma/*drug therapy/physiopathology MH - Double-Blind Method MH - Female MH - Forced Expiratory Volume MH - Humans MH - Indoleacetic Acids/adverse effects/pharmacokinetics/*therapeutic use MH - Male MH - Middle Aged MH - Pyridines/adverse effects/pharmacokinetics/*therapeutic use MH - Receptors, Immunologic/*antagonists & inhibitors MH - Receptors, Prostaglandin/*antagonists & inhibitors MH - Treatment Outcome OTO - NOTNLM OT - Asthma OT - Chemoattractant receptor-homologous molecule expressed on Th2 cells OT - Clinical trial EDAT- 2016/06/30 06:00 MHDA- 2017/10/31 06:00 CRDT- 2016/06/30 06:00 PHST- 2015/12/18 00:00 [received] PHST- 2016/06/16 00:00 [revised] PHST- 2016/06/19 00:00 [accepted] PHST- 2016/06/30 06:00 [entrez] PHST- 2016/06/30 06:00 [pubmed] PHST- 2017/10/31 06:00 [medline] AID - S1094-5539(16)30044-X [pii] AID - 10.1016/j.pupt.2016.06.005 [doi] PST - ppublish SO - Pulm Pharmacol Ther. 2016 Aug;39:54-63. doi: 10.1016/j.pupt.2016.06.005. Epub 2016 Jun 21.