Delving into the Latest Updates on Deleobuvir Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Deleobuvir, Deleobuvir sodium (JAN/USAN)

+ [5]

Target

NS5B polymerase

Mechanism

NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1Chronic hepatitis C genotype 1bHepatitis C+ [1]

Originator Organization

C.H. Boehringer Sohn AG & Co. KG

Active Organization-

Inactive Organization

Boehringer Ingelheim GmbHBoehringer Ingelheim International GmbHBoehringer Ingelheim Pharma GmbH & Co., KG

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure/Sequence

Molecular FormulaC34H33BrN6O3

InChIKeyBMAIGAHXAJEULY-UKTHLTGXSA-N

CAS Registry863884-77-9

View All Structures (2)

INTRODUCTIONCytochrome P450 (CYP) 2C8 is a drug metabolizing enzyme of major importance. The lipid-lowering drug gemfibrozil has been identified as a strong inhibitor of CYP2C8 in vivo. This effect is due to mechanism-based inhibition of CYP2C8 by gemfibrozil 1-O-β-glucuronide. In vivo, gemfibrozil is a fairly selective CYP2C8 inhibitor, which lacks significant inhibitory effect on other CYP enzymes. Gemfibrozil can, however, have a smaller but clinically meaningful inhibitory effect on membrane transporters, such as organic anion transporting polypeptide 1B1 and organic anion transporter 3. Areas covered: This review describes the inhibitory effects of gemfibrozil on CYP enzymes and membrane transporters. The clinical drug interactions caused by gemfibrozil and the different mechanisms contributing to the interactions are reviewed in detail. Expert opinion: Gemfibrozil is a useful probe inhibitor of CYP2C8 in vivo, but its effect on membrane transporters has to be taken into account in study design and interpretation. Moreover, gemfibrozil could be used to boost the pharmacokinetics of CYP2C8 substrate drugs. Identification of gemfibrozil 1-O-β-glucuronide as a potent mechanism-based inhibitor of CYP2C8 has led to recognition of glucuronide metabolites as perpetrators of drug-drug interactions. Recently, also acyl glucuronide metabolites of clopidogrel and deleobuvir have been shown to strongly inhibit CYP2C8.

01 Aug 2016·European Journal of Gastroenterology & HepatologyQ4 · MEDICINE

Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study

Q4 · MEDICINE

Article

Author: Angus, Peter ; Buti, Maria ; Kadus, Werner ; Mantry, Parvez ; Pockros, Paul J. ; Buynak, Robert J. ; Boecher, Wulf ; Dufour, Jean-Francois ; Wright, David ; Vinisko, Richard ; Soriano, Vicente ; Zeuzem, Stefan ; Mensa, Federico J. ; Stern, Jerry O.

BackgroundSOUND-C3 was a multicentre, open-label, phase 2b study exploring the safety and efficacy of the interferon-free combination of faldaprevir (an NS3/A4 protease inhibitor), deleobuvir (BI 207127, a non-nucleoside polymerase inhibitor) and ribavirin in treatment-naive patients with chronic hepatitis C virus (HCV) genotype-1 infection. Results in patients with HCV genotype-1b and in IL28B CC genotype patients with HCV genotype-1a have been described previously. This report describes the results in IL28B non-CC genotype patients with HCV genotype-1a.MethodsPatients were randomized to receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily (b.i.d.; N=26) or 600 mg three times daily (t.i.d.; N=25), and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12).ResultsIn each group, five patients completed 24 weeks of treatment. SVR12 rates were 19% (5/26) and 8% (2/25) in the b.i.d. and t.i.d. groups, respectively. On-treatment breakthrough [50% (13/26) and 68% (17/25) in the b.i.d. and t.i.d. groups, respectively] was the most frequent reason for not achieving SVR12. Adverse events led to premature treatment discontinuation in six (23%) patients in the b.i.d. group and in two patients (8%) in the t.i.d. group. The majority of adverse events were mild or moderate; the most frequently reported were nausea (67%), fatigue (35%) and diarrhoea (35%).ConclusionIn this small study, the interferon-free regimen of faldaprevir, deleobuvir and ribavirin resulted in high rates of virological breakthrough and low rates of SVR12 in IL28B non-CC genotype patients infected with genotype-1a HCV ( http://www.clinicaltrials.gov NCT01132313).

01 Mar 2016·Hepatology ResearchQ3 · MEDICINE

Open‐label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment‐naive patients with chronic hepatitis C virus genotype 1 infection

Q3 · MEDICINE

Article

Author: Ugai, Hiroyuki ; Kodani, Nobuyoshi ; Yatsuhashi, Hiroshi ; Omata, Masao

AimThe safety and efficacy of the NS3/4A protease inhibitor faldaprevir in combination with the non‐nucleoside NS5B polymerase inhibitor deleobuvir and ribavirin in Japanese treatment‐naive patients with chronic genotype 1 hepatitis C virus (HCV) infection was evaluated.MethodsIn this multicenter, open‐label phase 2 study, patients were assigned to 8 weeks of treatment with 80 mg (group 1) or 120 mg (group 2) faldaprevir once daily (q.d.) in combination with deleobuvir 600 mg twice daily and weight‐based ribavirin. This was followed by a 24‐week treatment with faldaprevir 120 mg q.d. in combination with peginterferon‐α‐2a and ribavirin. The primary objective was safety; virological response at weeks 4 and 8 was a secondary endpoint.ResultsTwelve and 13 patients were treated in group 1 and 2, respectively; all were infected with HCV genotype 1b. All patients experienced a drug‐related adverse event (AE). The frequency of individual events was generally numerically greater in group 2 than 1. The most common AEs were nausea (66.7%, group 1; 76.9%, group 2) and vomiting (33.3%, group 1; 61.5%, group 2). Virological response at weeks 4 and 8 was achieved by 11 (91.7%) patients in group 1; in group 2, 12 (92.3%) patients achieved virological response at week 4 and all at week 8. All patients who achieved the week 8 endpoint achieved sustained virological response at week 12.ConclusionFaldaprevir 80 or 120 mg q.d. in combination with deleobuvir and ribavirin was tolerable and had similar efficacy in Japanese patients with HCV genotype 1 infection. ClinicalTrials.gov: NCT01528735.

100 Deals associated with Deleobuvir Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D10622	Deleobuvir Sodium	-	DB14850

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic hepatitis C genotype 1	Phase 3	CA	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	NZ	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	GR	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	PT	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	ES	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	AU	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	DE	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	FR	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	BE	Boehringer Ingelheim GmbH	01 Nov 2012
Chronic hepatitis C genotype 1	Phase 3	GB	Boehringer Ingelheim GmbH	01 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01830127 (HCVerso3, Pubmed \| J Biol Chem \| PLoS One) Manual	Phase 2	Fibrosis \| Hepatitis C	35	Faldaprevir+Deleobuvir+Ribavirin (moderate hepatic impairment（Child-Pugh B [CPB]）)	(oasiurmvko) = wmboyxaybk luoxlzhsxb (jrpvypkjvd, 29.2 - 76.7) View more	Positive	28 Dec 2016
				Faldaprevir+Deleobuvir+Ribavirin (mild hepatic impairment（Child-Pugh A [CPA]）)	(oasiurmvko) = pazolazncw luoxlzhsxb (jrpvypkjvd, 38.6 - 83.6) View more
NCT01132313 (SOUND-C3, Pubmed \| Eur J Gastroenterol Hepatol) Manual	Phase 2	Hepatitis C	51	ribavirin+deleobuvir (receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily)	(rykubcioto) = gbyubnwurk lisvbzfrnx (kamdrhonsz ) View more	Positive	01 Aug 2016
				ribavirin+deleobuvir (600 mg three times daily)	(rykubcioto) = aqbnmnzvxn lisvbzfrnx (kamdrhonsz ) View more
NCT01525628 (CTgov)	Phase 1	Chronic hepatitis C genotype 1	72	pegylated interferon+BI 207127+BI 201335+tolbutamide+midazolam+caffeine+ribavirin (Group A)	pohhaxfuuc(uxgmwvwfmz) = wfipvshzwr nhbdqcklfn (flxnnotcxe, ardvsuwxem - mfwythhqez) View more	-	10 Jun 2016
				pegylated interferon+BI 207127+BI 201335+tolbutamide+midazolam+caffeine+ribavirin (Group B)	pohhaxfuuc(uxgmwvwfmz) = dsokzczqzd nhbdqcklfn (flxnnotcxe, nxwgccihyp - rtaotjdidc) View more
NCT01965431 (CTgov)	Phase 1	-	48	BI 207127+Faldaprevir (BI 207127+ Faldaprevir)	rylkkpyfuj(hmuuceufuh) = qdauusgqma uvkzovtsqo (iogqkpothd, wodehusnpa - glsacjoxyp) View more	-	14 Apr 2016
				Placebo+BI 207127+Faldaprevir (Placebo to BI 207127 + Placebo to Faldaprevir)	rylkkpyfuj(hmuuceufuh) = ziogqtttgf uvkzovtsqo (iogqkpothd, phcwkyjqkp - azesthsupk) View more
NCT01528735 (CTgov)	Phase 2	Hepatitis C, Chronic	25	Deleobuvir+Faldaprevir (600mg Deleobuvir and 80mg Faldaprevir)	mpjtvpghpx(yetgzbbmka) = csfhcqfamu wbpckzaygr (lvmvsowefh, mzdjgqxzeb - qpdjhkutop) View more	-	13 Apr 2016
				Deleobuvir+Faldaprevir (600mg Deleobuvir and 120mg Faldaprevir)	mpjtvpghpx(yetgzbbmka) = kgvozftpof wbpckzaygr (lvmvsowefh, qumxfezjip - plisgevzen) View more
NCT01941615 (CTgov)	Phase 1	-	18	Deleobuvir+Faldaprevir+Microgynon	oolplyvkva(ihvzrhtjkm) = swlywybzbb lzbrwnosrv (gyfthrsrcw, roghoitiue - jnhlylmkvo) View more	-	11 Apr 2016
NCT01957657 (CTgov)	Phase 1	Renal Insufficiency	4	Deleobuvir+Faldaprevir	kvuhfhtldk(dtruhrtdpz) = pvwyuvhotc zbdcprkrfv (pfdhsxmrhv, ywgnpmtubc - abuirrktfs) View more	-	11 Apr 2016
NCT01535638 (CTgov)	Phase 1	-	18	Deleobuvir (Deleobuvir Trial Formulation II)	dybpftswze(praqqseyos) = wfeqtdkuct xexshgpduf (wjiftsohgd, tiucprqfej - syswlupqhq) View more	-	11 Apr 2016
				Deleobuvir (Deleobuvir Final Formulation)	dybpftswze(praqqseyos) = vcvuqpaqch xexshgpduf (wjiftsohgd, wrirguucwx - wdllbkvnet) View more
NCT01737996 (CTgov)	Phase 1	-	32	Deleobuvir (400 mg Deleobuvir)	kyrdgkfhrr(duscbvfvbn) = oetxpebxqq uasodwlkwa (xqmleglewg, oijlmvrcrk - dhluoqsxum) View more	-	08 Apr 2016
				Deleobuvir (600 mg Deleobuvir)	kyrdgkfhrr(duscbvfvbn) = ndfhryhipk uasodwlkwa (xqmleglewg, dpfgkkfnck - ufxxyqogxh) View more
NCT01528735 (Pubmed \| Hepatol Res) Manual	Phase 2	Chronic hepatitis C genotype 1 First line	25	deleobuvir+ribavirin+peginterferon-α-2a+faldaprevir 80mg	(ieozhubyaf) = ploutcpfkn xstolpuhdj (vrvpralcvr ) View more	Positive	01 Mar 2016
				deleobuvir+ribavirin+peginterferon-α-2a+faldaprevir 120mg	(ieozhubyaf) = sbdiydqftn xstolpuhdj (vrvpralcvr ) View more