A Randomized, Double-Blind, Placebo- and Active-Controlled Crossover Study to Evaluate the Efficacy of JNJ 40929837 for the Treatment of Asthma Using a Bronchial Allergen Challenge Model - N/A

Start Date03 Nov 2010

Sponsor / Collaborator

Janssen-Cilag International NV

NCT01241422 / CompletedPhase 2

A Randomized, Double-Blind, Placebo- and Active-Controlled Crossover Study to Evaluate the Efficacy of JNJ 40929837 for the Treatment of Asthma Using a Bronchial Allergen Challenge Model

The purpose of this study is to evaluate the allergen-induced late asthmatic response (LAR), as measured by maximal percent fall in forced expiratory volume in 1 second, in participants with stable mild atopic asthma after treatment with JNJ 40929837 as compared to placebo.

Start Date01 Nov 2010

Sponsor / Collaborator

Johnson & Johnson Pharmaceutical Research & Development LLC

100 Clinical Results associated with JNJ-40929837

100 Translational Medicine associated with JNJ-40929837

100 Patents (Medical) associated with JNJ-40929837

Literatures (Medical) associated with JNJ-40929837

01 Oct 2014·Pulmonary Pharmacology & TherapeuticsQ3 · MEDICINE

Effects of JNJ-40929837, a leukotriene A4 hydrolase inhibitor, in a bronchial allergen challenge model of asthma

Q3 · MEDICINE

Article

Author: Jiang, J Z ; Thurmond, R ; Bertelsen, K ; Barnathan, E S ; Barchuk, W ; Silkoff, P E ; Fuhr, R ; Liu, X ; Fourie, A ; Lambert, J

Leukotriene B4 (LTB4) is a chemotactic mediator implicated in the pathogenesis of asthma. JNJ-40929837 is an oral inhibitor of LTA4 hydrolase, which catalyzes LTB4 production. We evaluated the effects of JNJ-40929837 in a human bronchial allergen challenge (BAC) model. In this double-blind, 3-period crossover study, 22 patients with mild, atopic asthma were randomized to one of three treatments per period: 100 mg/day JNJ-40929837 for 6 days followed by 50 mg/day on day 7; 10 mg/day montelukast for 6 days; and matched placebo. The BAC was performed on day 6 of each treatment period. Primary outcome was BAC-induced late asthmatic response (LAR) measured by maximal percent reduction in forced expiratory volume (FEV1) in one second. Secondary outcomes included early asthmatic response (EAR) by maximal percent reduction in FEV1, EAR and LAR evaluated by area under the FEV1/time curve (AUC0-2, AUC3-10, respectively), change in baseline FEV1 after 5-day treatment, safety, and correlation of JNJ-40929837 to the divalent cation ionophore A23187-stimulated whole blood LTB4 levels and sputum basal LTB4 levels. No significant differences were observed in the primary or secondary FEV1 endpoints with JNJ-40929837 versus placebo. Compared with placebo (n = 17, LS mean = 27.7), there was no significant attenuation of the maximal percent reduction in the LAR FEV1 with JNJ-40929837 (n = 16, LS mean = 28.6, P = 0.63) but montelukast (n = 17, LS mean = 22.6, P = 0.01) significantly attenuated the LAR. JNJ-40929837 substantially inhibited LTB4 production in whole blood, decreased sputum LTB4 levels and was well-tolerated. The number of adverse events leading to study withdrawal was the same in JNJ-40929837 and placebo groups. In conclusion, JNJ-40929837 demonstrated target engagement in blood and sputum. No significant impact in response to allergen inhalation was observed with JNJ-40929837 versus placebo.REGISTRATIONThis study is registered at ClinicalTrials.gov: NCT01241422.

01 Jul 2014·Toxicology and Applied PharmacologyQ3 · MEDICINE

Testicular distribution and toxicity of a novel LTA4H inhibitor in rats

Q3 · MEDICINE

Article

Author: La, D ; Ward, P D

JNJ 40929837, a novel leukotriene A4 hydrolase inhibitor in drug development, was reported to induce testicular toxicity in rats. The mechanism of toxicity was considered to be rodent specific and not relevant to humans. To further investigate this finding in rats, the distribution and toxicokinetics of JNJ 40929837 and its two metabolites, M1 and M2, were investigated. A quantitative whole body autoradiography study showed preferential distribution and retention of JNJ 40929837-derived radioactivity in the testes consistent with the observed site of toxicity. Subsequent studies with unlabeled JNJ 40929837 showed different metabolite profiles between the plasma and testes. Following a single oral 50mg/kg dose of JNJ 40929837, M2 was the primary metabolite in plasma whereas M1 was the primary metabolite in testes. The exposure of M1 was 386-fold higher in the testes compared to plasma whereas M2 had limited exposure in testes. Furthermore, the Tmax of M1 was 48h in testes suggesting a large accumulation potential of this metabolite in testes compared to plasma. Following six months of repeated daily oral dosing, M1 accumulated approximately five-fold in the testes whereas the parent did not accumulate. These results indicate that the toxicokinetic profiles of JNJ 40929837 and its two metabolites in testes are markedly different compared to plasma and support the importance of understanding the toxicokinetic profiles of compounds and their metabolites in organs/tissues where toxicity is observed.

100 Deals associated with JNJ-40929837

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	GB	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Nov 2010
Asthma	Phase 2	DE	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Nov 2010

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