Topic
Setipiprant
About: Setipiprant is a research topic. Over the lifetime, 19 publications have been published within this topic receiving 304 citations. The topic is also known as: Setipiprant.
Papers
TL;DR: CRTH2 is a G‐protein‐coupled receptor on T helper2 cells that mediates pro‐inflammatory effects of prostaglandin D2 in allergic responses.
Abstract: SummaryBackground
CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses.
Objective
To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses.
Methods
In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test.
Results
Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3–10 h)) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments.
Conclusion and Clinical Relevance
Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.
82 citations
TL;DR: A literature search of PubMed/MEDLINE and ClinicalTrial.gov was performed to gather information about active research on new treatments for alopecias and found that stem-cell research is advancing and the goal to create new follicles or refresh dormant follicles may be realized in the near future.
Abstract: Introduction Alopecia is a very common complaint in medical practice, which usually has a large psychological impact in patients. Treatment of alopecia is often difficult and frustrating for patients and clinicians owing to the slow growth rate of the hair, long treatment terms, limited efficacy, and possible adverse side effects. Areas covered This paper reviews the new and emerging treatments for two of the most common forms of alopecia, known as androgenetic alopecia and alopecia areata. A literature search of PubMed/MEDLINE and ClinicalTrial.gov was performed to gather information about active research on new treatments for alopecias. Websites of companies sponsoring clinical trials were also searched for interim result data. Expert opinion Many new therapies in two of the most common forms of hair loss have been developed and are currently being studied with encouraging results. In alopecia areata, JAK inhibitors are promising. The discovery of JAK inhibitors has prompted the research and identification of new molecules. In androgenetic alopecia, we are still looking for a topical treatment that is superior to topical minoxidil. However, stem-cell research is advancing and the goal to create new follicles or refresh dormant follicles may be realized in the near future.
35 citations
TL;DR: Findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks are presented.
Abstract: Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks. A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100–1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS). 579 participants were randomized in the Phase 2 trial (mean age 41.6–43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5–40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (−0.15 [95% CI −0.29, −0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (−0.02 [95% CI −0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile. The Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies. Trial registration NCT01241214 and NCT01484119
29 citations
TL;DR: In this entry‐into‐human study, setipiprant showed good tolerability and a favorable PK profile, thus warranting its development in the treatment of inflammatory disorders.
Abstract: Chemoattractant receptor-homologous molecule expressed on T helper (Th) 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key mediator in inflammatory disorders such as asthma and allergic rhinitis. In this study, we investigated the single- and multiple-dose tolerability and pharmacokinetics (PKs) of setipiprant, an orally active, potent, and selective CRTH2 antagonist. This randomized, double-blind, placebo-controlled study was performed in two parts in healthy male subjects. In study Part A, single oral doses of up to 2000 mg setipiprant or placebo were given to sequential groups of eight subjects each. Additionally, the impact of food on the PKs was investigated in one-dose group. In study Part B, two groups of subjects received 500 or 1000 mg setipiprant or placebo b.i.d. during 5.5 days. At regular intervals, tolerability variables and plasma and urine levels of setipiprant were determined. Setipiprant was well tolerated after single- and multiple-dose administration. Headache was the most frequently reported adverse event. No treatment effect on tolerability variables was observed. After single- and multiple-dose administration, setipiprant was rapidly absorbed and followed a biphasic elimination pattern with an elimination half-life between 10 and 18 h. Steady-state conditions were reached after 2-3 days and setipiprant did not accumulate. Exposure to setipiprant was lower in the presence of food. Urinary excretion of unchanged setipiprant did not exceed 7% of the administered dose. In this entry-into-human study, setipiprant showed good tolerability and a favorable PK profile, thus warranting its development in the treatment of inflammatory disorders.
17 citations
TL;DR: In this article, the use of peri-xanthenoxanthene (PXX), a simple and inexpensive dye, as an efficient photocatalyst was reported, allowing activation of a wide range of substrates, thus triggering useful radical reactions.
Abstract: Recent years have witnessed a continuous development of photocatalysts to satisfy the growing demand of photophysical and redox properties in photoredox catalysis, with complex structures or alternative strategies devised to access highly reducing or oxidising systems. We report herein the use of peri‐xanthenoxanthene (PXX), a simple and inexpensive dye, as an efficient photocatalyst. Its highly reducing excited state allows activation of a wide range of substrates, thus triggering useful radical reactions. Benchmark transformations such as the addition of organic radicals, generated by photoreduction of organic halides, to radical traps are initially demonstrated. More complex dual catalytic manifolds are also shown to be accessible: the β‐arylation of cyclic ketones is successful when using a secondary amine as organocatalyst, while cross‐coupling reactions of aryl halides with amines and thiols are obtained when using a Ni co‐catalyst. Application to the efficient two‐step synthesis of the expensive fluoro‐tetrahydro‐1H‐pyrido[4,3‐b]indole, a crucial synthetic intermediate for the investigational drug setipiprant, has been also demonstrated.
16 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 2 |
| 2019 | 1 |
| 2017 | 3 |
| 2016 | 1 |
| 2015 | 3 |