A Double-Blind, Randomised, Placebo Controlled, Two Period Cross-Over Study to Evaluate the Efficacy and Safety of Orvepitant in Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis

ORV-PF-01 is a two way, placebo controlled, cross-over study, to evaluate the effect of two doses of orvepitant on cough in patients with IPF.

Start Date01 Aug 2022

Sponsor / Collaborator

NeRRe Therapeutics Ltd.

[+1]

NCT04387981 / CompletedPhase 1

A Single Dose Study to Assess the Mass Balance Recovery, Absorption, Metabolism, and Excretion of [14C] Orvepitant in Healthy Male Subjects After Oral Dosing

This is a single centre, open-label, non-randomised study to assess the mass balance recovery, absorption, metabolism, and excretion of a single oral dose of [14C]-orvepitant in healthy male subjects. It is planned to enrol 6 subjects. Each subject will receive a single dose of 30 mg [14C] orvepitant containing not more than (NMT) 3.7 megabecquerel (MBq) [14C], administered as an oral solution in the fasted state. Subjects will be admitted in the evening on the day prior to [14C]-orvepitant administration and will be dosed in the morning following an overnight fast. It is planned that subjects will remain resident in the clinical unit until 168 hours post-dose (Day 8) when they will be discharged from the clinical unit. Through the resident period samples (blood, urine, faeces) will be collected and analysed for mass balance, total radioactivity, orvepitant levels. Metabolite profiling and ID will also be performed.

Start Date01 Jun 2020

Sponsor / Collaborator

NeRRe Therapeutics Ltd.

NCT03535662 / CompletedPhase 1

A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Male Participants to Determine the Effect of an Inhibitor of Cytochrome P450 3A and P Glycoprotein on Exposure to Orvepitant

A Phase 1 study to assess the effect of itraconazole, a strong inhibitor of CYP3A and P-glycoprotein, on the pharmacokinetics (PK) of orvepitant in healthy male volunteers.
Subjects will receive two single doses of 20mg orvepitant, once alone and once in combination with repeat doses of itraconazole. All subjects will follow the same sequence - orvepitant alone followed by orvepitant in combination with itraconazole.

Start Date08 Jun 2018

Sponsor / Collaborator

NeRRe Therapeutics Ltd.

100 Clinical Results associated with Orvepitant

100 Translational Medicine associated with Orvepitant

100 Patents (Medical) associated with Orvepitant

Literatures (Medical) associated with Orvepitant

01 Sep 2022·The American journal of managed care

Managed care considerations for the treatment of chronic cough

Article

Author: Burgoyne, Douglas S

Chronic cough (CC), defined as a daily cough lasting longer than 8 weeks in adults, is a common condition in the United States. CC is a diagnosis of exclusion associated with a substantial economic burden related to increased healthcare and medication utilization, decreased work productivity, a greater incidence of cough-related comorbidities, and reduced quality of life. CC treatment guidelines recommend stepwise treatment with specific nonpharmacologic therapies and pharmacologic agents. However, many patients may still have incomplete or no symptom relief, encounter response attenuation over time, or experience intolerable adverse effects. New targeted therapies for refractory CC are currently under development, including the purinergic 2X3 receptor antagonists gefapixant, BLU-5937, and sivopixant (S-600918) and the neurokinin-1 receptor antagonist orvepitant. These targeted agents may have improved efficacy and safety profiles, helping fill unmet treatment needs. If approved, managed care organizations must develop formulary placement and utilization management criteria based on clinical guideline recommendations, expert opinion, and cost-effectiveness analyses to support the clinically appropriate use of these targeted therapies for best patient outcomes.

15 Mar 2021·American journal of respiratory and critical care medicineQ1 · MEDICINE

Neurokinin-1 Receptor Inhibition and Cough

Q1 · MEDICINE

Communications

Author: Birring, Surinder S. ; Turner, Richard D.

Hence, a requirement for alternativen approaches, not only for CRC but also for cough associated with chronic and incurable diseases of the lung, such as lung cancer, is needed.The brain stem, there have been repeated observations in animal models of the activity of SP and NK1 inhibition on the cough reflex.Evidence for the efficacy of NK1 inhibitors for cough in patients with conditions other than lung cancer is so far very limited,although there are recent data. In an open-label study of 13 patients with CRC, orvepitant at 30 mg once daily for 4 wk was associated with a 26% reduction in cough frequency.The current study has demonstrated that there is still a lot to learn about NK1 antagonists, which may still yet have potential as much-needed novel treatments for cough.

01 Feb 2020·BMJ openQ4 · MEDICINE

Neurokinin-1 antagonist orvepitant for EGFRI-induced pruritus in patients with cancer: a randomised, placebo-controlled phase II trial

Q4 · MEDICINE

ArticleOA

Author: Wood, Andrew ; Guglielmini, Pamela ; Vincenzi, Bruno ; Tonini, Giuseppe ; Lacouture, Mario E ; Jackson, David ; Ständer, Sonja ; Harris, Peter ; Ratti, Emiliangelo ; Duggal, Ajay ; Trower, Mike

Objective:

To evaluate the efficacy of orvepitant (10 or 30 mg given once daily, orally for 4 weeks), a neurokinin-1 receptor antagonist, compared with placebo in reducing the intensity of epidermal growth factor receptor inhibitor (EGFRI)-induced intense pruritus.

Design:

Randomised, double-blind, placebo-controlled clinical trial.

Setting:

15 hospitals in Italy and five hospitals in the UK.

Participants:

44 patients aged ≥18 years receiving an EGFRI for a histologically confirmed malignant solid tumour and experiencing moderate or intense pruritus after EGFRI treatment.

Intervention:

30 or 10 mg orvepitant or placebo tablets once daily for 4 weeks (randomised 1:1:1).

Primary and secondary outcome measures:

The primary endpoint was change from baseline in mean patient-recorded numerical rating scale (NRS) score (over the last three recordings) at week 4. Secondary outcome measures were NRS score, verbal rating scale score, Skindex-16 and Leeds Sleep Evaluation Questionnaire at each study visit (baseline, weeks 1, 4, 8); rescue medication use; EGFRI dose reduction; and study withdrawal because of intense uncontrolled pruritus.

Results:

The trial was terminated early because of recruitment challenges; only 44 of the planned 90 patients were randomised. All patients were analysed for efficacy and safety. Mean NRS score change from baseline to week 4 was −2.78 (SD: 2.64) points in the 30 mg group, −3.04 (SD: 3.06) points in the 10 mg group and −3.21 (SD: 1.77) points in the placebo group; the difference between orvepitant and placebo was not statistically significant. No safety signal was detected. Adverse events related to orvepitant (asthenia, dizziness, dry mouth, hyperhidrosis) were all of mild or moderate severity.

Conclusions:

Orvepitant was safe and well tolerated. No difference in NRS score between the orvepitant and placebo groups was observed at the week 4 primary endpoint. A number of explanations for this outcome are possible.

Trial registration number:

EudraCT2013-002763-25.

News (Medical) associated with Orvepitant

07 Jul 2021

·medcitynews.com

NeRRe nabs £20M to test chronic cough drug in patients with a fatal lung disease

Patients who have the rare and fatal lung disorder idiopathic pulmonary fibrosis (IPF) have an uncontrolled and persistent cough that’s unresponsive to any therapies. NeRRe Therapeutics has clinical data suggesting its experimental drug reduces cough frequency and it has raised £20M (about $27.6 million) to see if the therapy can help the coughing of IPF patients. The Stevenage, U.K.-based company describes the new funding announced Wednesday as a Series B2 financing round. It plans to apply the cash toward the drug, orvrepitant, and clinical testing that’s planned for patients diagnosed with IPF. IPF is a form of fibrosis affecting the lungs. The disorder causes thickening and hardening of connective tissue, which in turn leads to scarring of the lungs. There is no cure, other than a lung transplant. Treatment is mainly managing the symptoms, though several biotechs have entered clinical trials testing drugs intended to addressing mechanisms that drive fibrosis. That’s not what NeRRe is pursuing. The company aims to address the persistent coughing that IPF patients experience as their disease progresses. Orvepitant is a small molecule designed to block the neurokinin 1 (NK-1) receptor. NK-1 inhibitors are already available for preventing nausea and vomiting. According to NeRRe, dysfunction of this receptor is also associated with the neural hypersensitivity that leads to chronic cough. Blocking NK-1 is intended to reduce the hypersensitivity underlying chronic cough. Nerre’s planned Phase 2 study in IPF patients is a second go-around for orvepitant, which the company initially studied as a treatment for chronic cough that is resistant to treatment. That placebo-controlled Phase 2 study enrolled 319 patients who were given the once-daily pill for 12 weeks. In results reported in 2019, orvepitant failed to achieve the main goal, at week 12, of reducing cough frequency while patients were awake. Despite failing the clinical trial, NeRRe pointed to other measures as showing improvement in chronic cough symptoms, including cough severity and urge to cough. On its website, NeRRE says that at 30 mg, the highest dose tested, the data trended toward showing significance in patients who had higher cough frequencies at the beginning of the study. Since that study, other clinical research in chronic cough has shown similar results. It’s in that context that NeRRe plans to proceed with Phase 2 testing in patients with IPF, a disease characterized by a high frequency of coughing. NeRRe is a spinout of GlaxoSmithKline. All of the biotech’s drugs are NK inhibitors that originally came from the labs of the pharmaceutical giant. The new cash infusion for NeRRe comes nearly a year after its own spinout company, KaNDy Therapeutics, was acquired by Bayer for $425 million up front. KaNDy’s drug, now dubbed BAY3427080, is a potential treatment for the night sweats and hot flashes that are symptoms of menopause. The small molecule, designed to block the NK-1 and NK-3 receptors, is in mid-stage clinical testing. The new NeRRe funding was led by new investor Columbus Venture Partners and earlier investors Advent Life Sciences, Fountain Healthcare Partners, Forbion Capital Partners, OrbiMed and the UK Government’s Future Fund. NeRRe said most of the proceeds will go toward Phase 2 clinical development of orvepitant as a treatment for chronic cough associated with IPF. Photo credit: Jackie Niam, Getty Images

Small molecular drug

07 Jul 2021

·endpts.com

After selling its spinout to Bayer in a $875M-plus deal, NeRRe Therapeutics grabs $28M for some 'unfinished business'

Some biotech CEOs find themselves out of jobs following a buyout. Not Mary Kerr. In fact, after Bayer dished out $425 million in cash to buy KaNDy Therapeutics and its menopause treatment last August — which was spun out from NeRRe Therapeutics and run by that exact same team — her entire crew quickly got back to work. Like the drug that Bayer bought (dubbed NT-814), the three other drugs sitting in NeRRe’s pipeline are neurokinin-targeting compounds that had originally hailed from GlaxoSmithKline. Among them, orvepitant for chronic cough was the lead candidate, positioned just slightly ahead of NT-814 as the lead candidate. “So for us, NeRRe and orvepitant (are) really unfinished business,” Kerr told Endpoints News. With KaNDy now completely behind them, the small and virtual team of nine has raised £20 million ($27.6 million) to steer the drug toward the cusp of Phase III. Top of mind will be starting a mid-stage trial to test orvepitant as a treatment for disabling chronic cough associated with idiopathic pulmonary fibrosis (IPF) — a patient population NeRRe has zeroed in on after reviewing a failed Phase IIb study in refractory or unexplained chronic cough. While the flop on the primary endpoint of reduction in cough frequency was disappointing, Kerr said, all the secondaries were “extremely positive” and “both clinically and statistically significant,” particularly in patient-reported outcomes like the urge to cough, cough severity and quality of life. As it dug into the data, NeRRe concluded that investigators had difficulty detecting a signal among low frequency coughers, which wasn’t an issue with high frequency coughers. Notably, other drugmakers in the space such as Bellus and Merck have reported similar findings. “It’s a bit like asthma,” she said. “If you want to see a benefit in asthma, the studies are done in moderate to severe patients because the signal needs to be high enough in order to see a reduction.” Chronic cough associated with IPF is “the most disabling of all chronic coughs,” Kerr noted. On top of selecting a new patient population, NeRRe is also planning to go with a different primary endpoint for the upcoming study, developing a new metric for efficacy based on patient-reported outcomes. An observational study is underway to aid in the development, and it expects to send data ahead to the FDA for review by the fourth quarter. If it all goes well, the biotech would read out new Phase II data near the end of 2023 — and the new cash is designed to keep all options open regarding further financing or potential partnerships. Columbus Venture Partners, a new investor, led the Series B2, which also featured existing backers Advent Life Sciences, Fountain Healthcare Partners, Forbion Capital Partners, OrbiMed and the UK Government’s Future Fund.

100 Deals associated with Orvepitant

External Link

KEGG	Wiki	ATC	Drug Bank
D09650	Orvepitant	-	DB12427

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic cough	Phase 2	NL	NeRRe Therapeutics Ltd.	01 Aug 2022
Idiopathic Pulmonary Fibrosis	Phase 2	US	NeRRe Therapeutics Ltd.	01 Aug 2022
Idiopathic Pulmonary Fibrosis	Phase 2	NL	NeRRe Therapeutics Ltd.	01 Aug 2022
Idiopathic Pulmonary Fibrosis	Phase 2	GB	NeRRe Therapeutics Ltd.	01 Aug 2022
Dermatitis, Atopic	Phase 2	-	NeRRe Therapeutics Ltd.	01 May 2018
Pruritus	Phase 2	-	NeRRe Therapeutics Ltd.	01 May 2018
Refractory chronic cough	Phase 2	US	NeRRe Therapeutics Ltd.	22 May 2017
Refractory chronic cough	Phase 2	CA	NeRRe Therapeutics Ltd.	22 May 2017
Refractory chronic cough	Phase 2	GB	NeRRe Therapeutics Ltd.	22 May 2017
Stress Disorders, Post-Traumatic	Phase 2	US	GSK Plc	02 Nov 2009

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02993822 (VOLCANO-2, CTgov)	Phase 2	Refractory chronic cough	315	Orvepitant Maleate (Orvepitant 10mg)	myaiixvsmk(xqwlgdbcpb) = qzbumbwlsi hprewezlmr (axnfztmmze, xloilmnbwj - vsqdbgwbjs) View more	-	26 Apr 2022
				Orvepitant Maleate (Orvepitant 20mg)	myaiixvsmk(xqwlgdbcpb) = iyxrbjhcqr hprewezlmr (axnfztmmze, ppmawyblig - tghhaajkef) View more
NCT02993822 (VOLCANO-2, Corporate Publications) Manual	Phase 2	Chronic cough	315	Orvepitant	hojnzhcjkt(lmpfhnozwj) = reduction not significant rgcfpmnxsj (xvirdblkbl ) View more	Positive	07 Jun 2019
				Placebo
NCT00880048 (CTgov)	Phase 2	Depressive Disorder, Major	343	Placebo	kkxibvomyd(parfhdlyka) = bsovkoiokg hwvhpzrqfd (uusumfyyiz, simotojqrk - ehoncljoox) View more	-	13 Oct 2017
NCT00880399 (CTgov)	Phase 2	Depressive Disorder, Major	328	placebo (Placebo)	ovycebfryc(loajtdqrup) = yigajaivcn zaxhtozali (iqotaduvtb, czxdrbtrji - pkosbcctyr) View more	-	12 Sep 2017
				orvepitant (Orvepitant 30 mg)	ovycebfryc(loajtdqrup) = uzmgtcoulk zaxhtozali (iqotaduvtb, axgnvlhirn - rhelrdyblb) View more
NCT01000493 (CTgov)	Phase 2	Stress Disorders, Post-Traumatic	132	Placebo	hsrqqafvxd(obslhpbzzk) = ritzeysrcm lflkrpmego (pikaizeuwr, htykmfyvjg - ecclhdaraa) View more	-	01 Sep 2017

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