A Phase 3, Randomized, Open-label, Multicenter Trial to Evaluate the Efficacy, Safety, and Tolerability of 4-month and 6-month Quabodepistat-containing Regimens for Rifampicin-resistant/Multidrug-resistant Pulmonary Tuberculosis

This study aims to assess quabodepistat-based treatment regimens for RR/MDR-TB. The study will enroll adults and adolescents with rifampicin-resistant or multidrug-resistant pulmonary TB. The main goal is to see if a new drug called quabodepistat, when combined with other TB drugs, can shorten treatment duration to 4 months and be as effective and safer than current WHO endorsed treatment regimen given for 6-months. The study will compare different drug combinations in two groups of patients: those whose TB is sensitive to fluoroquinolones and those whose TB is resistant to fluoroquinolones. Participants will be randomly assigned to receive either the new treatment or the standard treatment. The study will last for 16 months for each participant and will measure how well the treatments work and how safe they are.

Start Date16 Oct 2025

Sponsor / Collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

NCT06114628

/ RecruitingPhase 2IIT

A Seamless Phase 2B/C Platform Trial to Evaluate Multiple Regimens and Durations of Treatment in Pulmonary Tuberculosis

The UNITE4TB consortium is a group of universities and pharmaceutical companies funded by the European Union. This consortium are carrying out a trial to find better and faster ways to treat tuberculosis (TB). The standard treatment for TB takes 24 weeks and uses four drugs. The consortium want to find new treatments that are faster but just as safe and effective.
In the trial, two new drugs will be used, BTZ-043 and GSK3036656, along with the drugs that are already used to treat TB in a variety of combinations (11 different combinations initially). These new drugs have worked well in tests with animals and have reduced the amount of TB bacteria in people's sputum/phlegm when used alone for two weeks. These new drugs will be used in combination with other TB drugs for a longer time (up to 16 weeks) in people with TB. The UNITE4TB consortium want to see if they work well and are safe.
This trial will take place at sites across the world and will involve people with TB of the lungs that would usually respond well to the standard treatment. But the new treatments being tested might also work for people with drug resistant TB, that's harder to treat.
The trial has two parts. In the first part, different combinations of drugs will be tried on up to 700 people for 16 weeks. These combinations will be compared to the standard 24-week treatment to see which ones work the best and are safe.
In the second part, the best combinations from the first part will be taken to try to find out what the best length of time is to give the treatment for. These combinations will be tried on up to 1800 people giving them either 8, 10, 12, 14 or 16 weeks treatment. The investigators will follow these people for a total of 72 weeks to make sure the treatment is working.
The UNITE4TB consortium hope that this trial will find new treatments that are fast, safe, and effective for both regular TB and resistant TB. If it works, it can then be tested again in a bigger trial to be sure.

Start Date09 Jan 2024

Sponsor / Collaborator

University College London

[+22]

100 Clinical Results associated with Quabodepistat

100 Translational Medicine associated with Quabodepistat

100 Patents (Medical) associated with Quabodepistat

Literatures (Medical) associated with Quabodepistat

22 Apr 2025·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Verapamil and its metabolite norverapamil inhibit the Mycobacterium tuberculosis MmpS5L5 efflux pump to increase bedaquiline activity

Article

Author: Cook, Gregory M. ; Ramakrishnan, Lalita ; Fountain, Adam J. ; McNeil, Matthew B. ; Edelstein, Paul H. ; Waller, Natalie J. E. ; Jowsey, William ; Troll, Mark ; Cheung, Chen-Yi ; Chrisp, Michael T.

Bedaquiline is the cornerstone of a new regimen for the treatment of drug-resistant tuberculosis. However, its clinical use is threatened by the emergence of bedaquiline-resistant strains of Mycobacterium tuberculosis . Bedaquiline targets mycobacterial ATP synthase but the predominant route to clinical bedaquiline resistance is via upregulation of the MmpS5L5 efflux pump due to mutations that inactivate the transcriptional repressor Rv0678 . Here, we show that the MmpS5L5 efflux pump reduces susceptibility to bedaquiline as well as its new, more potent derivative TBAJ-876 and other antimicrobial substrates, including clofazimine and the DprE1 inhibitors PBTZ-169 and OPC-167832. Furthermore, the increased resistance of Rv0678 mutants stems entirely from increased MmpS5L5 expression. These results highlight the potential of a pharmacological MmpS5L5 inhibitor to increase drug efficacy. Verapamil, primarily used as a calcium channel inhibitor, is known to inhibit diverse efflux pumps and to potentiate bedaquiline and clofazimine activity in M. tuberculosis . Here, we show that verapamil potentiates the activity of multiple diverse MmpS5L5 substrates. Using biochemical approaches, we demonstrate that verapamil does not exert this effect by acting as a disruptor of the protonmotive force used to power MmpS5L5, as previously proposed, suggesting that verapamil inhibits the function of the MmpS5L5 pump. Finally, norverapamil, the major verapamil metabolite, which has greatly reduced calcium channel activity, has equal potency in reducing resistance to MmpS5L5 substrates. Our findings highlight verapamil’s potential for enhancing bedaquiline TB treatment, for preventing acquired resistance to bedaquiline and other MmpS5L5 substrates, while also providing the impetus to identify additional MmpS5L5 inhibitors.

01 Apr 2025·LANCET INFECTIOUS DISEASES

Safety, pharmacokinetics, and early bactericidal activity of quabodepistat in combination with delamanid, bedaquiline, or both in adults with pulmonary tuberculosis: a randomised, active-controlled, open-label trial

Article

Author: Narunsky, Kim ; De Jager, Veronique ; Zheng, Bo ; Diacon, Andreas H ; Liu, Yongge ; Hafkin, Jeffrey ; Stinson, Kelly W ; Moodley, V Mischka ; Dawson, Rodney

BACKGROUND:

Quabodepistat (formerly OPC-167832) showed potent activity in preclinical studies and in the first stage of an early bactericidal activity study in adults with smear-positive, drug-susceptible pulmonary tuberculosis. Stage 2 of this study was designed to evaluate the safety, tolerability, pharmacokinetics, and early bactericidal activity of quabodepistat in combination with delamanid, bedaquiline, or both versus rifampicin, isoniazid, ethambutol, and pyrazinamide combination therapy for 14 days.

METHODS:

Stage 2 of this open-label, active-controlled, randomised, parallel-group study was conducted at two research sites in South Africa in adults (aged 18-64 years) with drug-susceptible pulmonary tuberculosis. Eligible participants had a BMI of 16-32 kg/m² and the ability to produce an adequate volume of sputum (≥10 mL overnight) and were excluded if they had drug-resistant tuberculosis or previous treatment for Mycobacterium tuberculosis within the past 3 years. Participants were centrally randomly assigned via interactive web response technology system, with no stratification, into four treatment groups in a ratio of 14:14:14:4 (quabodepistat 30 mg plus delamanid 300 mg, quabodepistat 30 mg plus bedaquiline 400 mg, or quabodepistat 30 mg plus delamanid 300 mg plus bedaquiline 400 mg orally once daily for 14 days, or rifampicin, isoniazid, ethambutol, and pyrazinamide combination therapy [control] according to local standard of care for 20 days). The primary outcomes were safety and tolerability during and after 14 days of treatment in all participants who received any study medication and pharmacokinetics at day 1 and day 14 in participants in the quabodepistat groups with adequate data for deriving pharmacokinetics parameters. The main secondary outcome was bactericidal activity from baseline to day 14 in all eligible participants who were quantitatively culture-positive at baseline. The study was not powered for formal statistical hypothesis testing; therefore, data were summarised by treatment group with descriptive statistics. This study is registered with ClinicalTrials.gov (NCT03678688) and is closed to new participants.

FINDINGS:

98 participants were screened for entry into stage 2 of the trial between Feb 1, 2021, and Jan 27, 2022, of whom 46 were randomly assigned (14 to each quabodepistat group, 4 to the control group) and 44 received at least one dose of study medication (one patient excluded from the quabodepistat plus delamanid and quabodepistat plus bedaquiline groups). 32 (73%) of 44 participants had at least one treatment-emergent adverse event. Most events (30/32 [94%]) were mild or moderate; the most common treatment-emergent adverse events (≥2 participants; not related to study drugs) were headache (4/44 [9%]), dizziness (3/44 [7%]), abdominal pain (2/44 [5%]), pruritus (2/44 [5%]), and nausea (2/44 [5%]). Two serious adverse events were reported in two participants in the quabodepistat and bedaquiline cohort (anal abscess [n=1], pneumothorax [n=1]); both were deemed not related to study drug. Quabodepistat exposure was minimally affected by coadministration of delamanid or bedaquiline, with lower exposure in the quabodepistat and bedaquiline cohorts (maximum plasma concentration for quabodepistat plus delamanid 208 ng/mL [SD 61; n=11]; quabodepistat plus bedaquiline 175 ng/mL [31; n=10]; quabodepistat plus delamanid plus bedaquiline 183 ng/mL [52; n=11]). Maximum quabodepistat concentrations were achieved approximately 3 h after administration in all combinations. Mean elimination half-life was shorter in combinations with bedaquiline than without bedaquiline (12·3-14·5 h vs 15·2 h). Mean changes from baseline to day 14 of sputum log₁₀ colony-forming units per mL were -2·73 (SD 1·51) for quabodepistat plus delamanid plus bedaquiline (n=12) and -2·71 (SD 0·92) for control (n=19); mean change was -2·17 (SD 1·83) in the quabodepistat plus delamanid cohort (n=11) and -1·97 (SD 1·29) in the quabodepistat plus bedaquiline cohort (n=11).

INTERPRETATION:

In this 14-day trial, quabodepistat plus delamanid plus bedaquiline, a novel three-drug combination, appeared to be safe, well tolerated, and provided robust early bactericidal activity in adults with drug-susceptible pulmonary tuberculosis. Further evaluation is warranted.

FUNDING:

Otsuka Pharmaceutical Development & Commercialization and the Bill & Melinda Gates Foundation.

01 Apr 2025·LANCET INFECTIOUS DISEASES

First data of a quabodepistat containing novel regimen for drug-susceptible tuberculosis

Article

Author: Naidoo, Kogieleum ; Perumal, Rubeshan

News (Medical) associated with Quabodepistat

06 Nov 2025

·www.otsuka.co.jp

Otsuka Announces First Participants Enrolled in Phase 3 Clinical Trial Evaluating Investigational Compound Quabodepistat for Drug-resistant Pulmonary Tuberculosis

Otsuka Pharmaceutical Co. Ltd., (Otsuka) and its U.S. subsidiary, Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) today announced that the first participants have been successfully enrolled and dosed in its Phase 3 clinical trial evaluating quabodepistat, an investigational compound for the treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB). TB, and particularly its resistant forms, remains a major global health challenge. According to the World Health Organization, over 10 million people fall ill with tuberculosis each year, most of whom live in low- to middle-income countries. Despite being preventable and curable, 1.25 million people die from the disease annually1. The Phase 3 trial named QUANTUM-TB (Quabodepistat Accelerating New Treatments for Multidrug- Resistant Tuberculosis), is a randomized study designed to evaluate efficacy, safety, and tolerability of quabodepistat-containing regimens in adults and adolescents aged 14 and above. The primary goal of the quabodepistat clinical development program is to develop an efficacious, shorter-duration, less toxic, and well-tolerated regimen for treatment of people suffering from MDR-TB. The trial will compare a quabodepistat-based regimen administered for 17 weeks in participants with fluoroquinolone-sensitive MDR-TB and for 26 weeks in participants with fluoroquinolone-resistant MDR-TB against the corresponding WHO standards of care. The first participants were enrolled in the Philippines, marking a significant milestone in the development of this investigational compound. The trial is scheduled to be conducted at over 30 sites in several countries across the globe, including Japan. "We are excited to begin this important trial and are deeply grateful to the participants and investigators," said Masanori Kawasaki, senior vice president & operating officer, associate general manager (Research) at Otsuka. "This trial represents a critical step toward addressing the unmet needs of individuals suffering from drug-resistant TB." This Phase 3 clinical trial is registered on ClinicalTrials.gov under the identifier NCT07209761. More information is available at: https://clinicaltrials.gov/study/NCT07209761 1Global tuberculosis report 2024. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.

Phase 3

05 Nov 2025

·www.drugs.com

Otsuka Announces First Participants Enrolled in Phase 3 Clinical Trial Evaluating Investigational Compound Quabodepistat for Drug-resistant Pulmonary Tuberculosis

PRINCETON, N.J. and TOKYO, JAPAN — November 5, 2025 – Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and our parent company Otsuka Pharmaceutical Co. Ltd., (Otsuka) today announced that the first patients have been successfully enrolled and dosed in its Phase 3 clinical trial evaluating quabodepistat, an investigational compound for the treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB). TB, and particularly its resistant forms, remains a major global health challenge. According to the World Health Organization, 10 million people fall ill with tuberculosis each year, most of whom live in low- to middle-income countries. Despite being preventable and curable, 1.25 million people die from the disease annually. The Phase 3 trial named QUANTUM-TB ( Qu abodepistat A ccelerating N ew T reatments for M ultidrug- Resistant Tuberculosis ), is a randomized study designed to evaluate efficacy, safety, and tolerability of quabodepistat-containing regimens in adults and adolescents aged 14 and above. The primary goal of the quabodepistat clinical development program is to develop an efficacious, shorter-duration, less toxic, and well-tolerated regimen for treatment of people suffering from MDR-TB. The trial will compare a quabodepistat-based regimen administered for 17 weeks in participants with fluoroquinolone-sensitive MDR-TB and for 26 weeks in participants with fluoroquinolone-resistant MDR-TB against the corresponding WHO standards of care. The first participants were enrolled in the Philippines, marking a significant milestone in the development of this investigational compound. The trial is scheduled to be conducted at over 30 sites in several countries across the globe, including Japan. “We are excited to begin this important trial and are deeply grateful to the participants and investigators,” said Masanori Kawasaki, senior vice president & operating officer, associate general manager (Research) at Otsuka. “This trial represents a critical step toward addressing the unmet needs of individuals suffering from drug-resistant TB.” This Phase 3 clinical trial is registered on ClinicalTrials.gov under the identifier NCT07209761 . More information about the trial can be found at https://clinicaltrials.gov/study/NCT07209761 . About Otsuka Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual’s potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka’s unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide . Otsuka established a presence in the U.S. in 1973 and today our U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,250 employees develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 35,340 people worldwide and had consolidated sales of approximately USD 14.7 billion in 2024. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS . Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/. Source: Otsuka Pharmaceutical Co., Ltd.

Phase 3

22 Mar 2024

·www.otsuka.co.jp

Otsuka Announces Interim Data from Phase 2b/c Trial Indicating New Investigational Compound May Shorten Tuberculosis Treatment

Otsuka Pharmaceutical, Co. Ltd. And our U.S.-based subsidiary Otsuka Pharmaceutical Development & Commercialization, Inc., announce that interim data from a Phase 2b/c trial exploring quabodepistat (QBS), in combination with delamanid and bedaquiline, for the treatment of pulmonary tuberculosis (TB) is positive and may shorten the duration of TB treatment for patients. QBS is an investigational anti-tuberculosis compound which has a new mechanism of action that interferes with the cell-wall structure of the bacteria causing TB.1,2 Worldwide, TB is the second leading infectious fatal disease after COVID-19. The interim analysis -- which was presented at the 2024 Conference on Retroviruses and Opportunistic Infections in Denver, Colorado in early March -- demonstrated that a four-month regimen of QBS, in combination with delamanid and bedaquiline, can achieve similar safety and efficacy, compared to the six-month, standard-of-care four-drug regimen in participants with drug-susceptible TB.3 These results show that sputum culture conversion rates -- or effectiveness of the treatment combination in killing the bacteria -- at the end of treatment in the pooled QBS-based, three-drug regimen arms were on par with existing standard four-drug TB treatment. The three-drug QBS-based arms were well-tolerated, with no serious treatment emergent adverse events reported, related to the regimens.3 The ongoing study, supported by Otsuka and the Bill & Melinda Gates Foundation, is being held across six clinical research sites in South Africa. Otsuka and the foundation have been collaborating to end TB worldwide, and the foundation contributed to initial funding for the early development of quabodepistat.2,3 "Otsuka is encouraged by these positive interim data and is pleased to continue working with the support of the Bill & Melinda Gates Foundation to identify safe and effective treatment options for patients living with tuberculosis," said Masanori Kawasaki, global project leader of TB Project at Otsuka Pharmaceutical. "We are deeply thankful to the patients, their families and the clinicians who participated in this important clinical research study." The trial (NCT05221502) was a multicenter, Phase 2b/c, open-label, randomized, dose-finding trial designed to evaluate the safety and efficacy of a four-month regimen of OPC-167832 (quabodepistat) in combination with delamanid and bedaquiline in patients with drug-susceptible pulmonary tuberculosis in comparison with six months standard treatment. Full results of this phase 2b/c, randomized trial are expected by the end of 2024.2,3 *1Hariguchi N et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor. Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19. *2Dawson R et al. Quabodepistat in Combination with Delamanid and Bedaquiline in Participants with Drug-Susceptible Pulmonary Tuberculosis: protocol for a multicenter, phase 2 b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy. Trials. 2024 Jan 19;25(1):70. *3Dawson R et al. A 4-month Regimen of Quabodepistat, Delamanid and Bedaquiline for Pulmonary TB: Interim Results. Conference on Retroviruses and Opportunistic Infections (CROI), 5 March 2024, Denver, Co., USA; Abstract no. 163. *4World Health Organization, Tuberculosis key facts　https://www.who.int/news-room/fact-sheets/detail/tuberculosis

Phase 2Clinical ResultPhase 3

100 Deals associated with Quabodepistat

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Indication	Highest Phase	Country/Location	Organization	Date
Multidrug resistant pulmonary tuberculosis	Phase 3	United States	Otsuka Pharmaceutical Development & Commercialization, Inc.	16 Oct 2025
Pulmonary Tuberculosis	Phase 2	South Africa	Otsuka Pharmaceutical Development & Commercialization, Inc.	12 Apr 2022
Tuberculosis	Phase 1	Bulgaria	Otsuka Pharmaceutical Development & Commercialization, Inc.	13 Nov 2025
Tuberculosis, Multidrug-Resistant	IND Approval	China	Otsuka Pharmaceutical Co., Ltd.	01 Sep 2025

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03678688 (CTgov)	Phase 1/2	Pulmonary Tuberculosis	122	10 mg OPC-167832 (Stage 1: 10 mg OPC-167832)	iduuudcxwt(olimaquomg) = kepsmquhgw matgimytpj (rgkmetclyq, 0.98) View more	-	18 Nov 2023
				30 mg OPC-167832 (Stage 1: 30 mg OPC-167832)	iduuudcxwt(olimaquomg) = qotujywdtk matgimytpj (rgkmetclyq, 1.01) View more

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