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Trial record 26 of 170 for:    "Pulmonary Tuberculosis"

A Phase 1/2 Trial of Multiple Oral Doses of OPC-167832 for Uncomplicated Pulmonary Tuberculosis

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ClinicalTrials.gov Identifier: NCT03678688
Recruitment Status : Recruiting
First Posted : September 20, 2018
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:
This trial will evaluate the safety, tolerability, pharmacokinetics, and efficacy of multiple oral doses of OPC-167832 in subjects with uncomplicated, smear-positive, drug-susceptible pulmonary tuberculosis (TB).

Condition or disease Intervention/treatment Phase
Pulmonary TB Drug: 10 mg OPC-167832 Drug: 30 mg OPC-167832 Drug: 90 mg OPC-167832 Drug: 270 mg OPC-167832 Drug: RHEZ Drug: Low dose OPC-167832 plus 200 mg delamanid Drug: High dose OPC-167832 plus 200 mg delamanid Drug: 200 mg delamanid alone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This will be a multiple-dose trial of OPC-167832 with 2 stages.

Stage 1 is a multiple ascending dose trial planned to be conducted in 4 sequential cohorts of 18 participants each. There will be 2 arms (OPC-167832, RHEZ) in each cohort.

Stage 2 will be a parallel group comparison of 4 treatment regimens: 1) low dose OPC-167832 plus delamanid 2) high dose OPC-167832 plus delamanid 3) delamanid only 4) RHEZ.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Active-controlled, Randomized, Open-label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Oral Doses of OPC-167832 Tablets in Subjects With Uncomplicated, Smear-positive, Drug-susceptible Pulmonary Tuberculosis
Actual Study Start Date : October 25, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Active Comparator: Stage 1 and Stage 2: RHEZ Drug: RHEZ

RHEZ will be used in both Stage 1 and Stage 2. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Participants will receive a single-dose from Day 1 through Day 20. The total number of tablets per day will be based on the pretreatment body weight:

  • Participants weighing 30 to 37 kg will receive 2 tablets per day
  • Participants weighing 38 to 54 kg will receive 3 tablets per day
  • Participants weighing 55 to 70 kg will receive 4 tablets per day
  • Participants weighing > 70 kg will receive 5 tablets per day

Experimental: Stage 1 Cohort 1 Drug: 10 mg OPC-167832
Once daily oral dose of 10 mg OPC-167832 from Day 1 through Day 14.

Experimental: Stage 1 Cohort 2 Drug: 30 mg OPC-167832
Once daily oral dose of 30 mg OPC-167832 from Day 1 through Day 14.

Experimental: Stage 1 Cohort 3 Drug: 90 mg OPC-167832
Once daily oral dose of 90 mg OPC-167832 from Day 1 through Day 14.

Experimental: Stage 1 Cohort 4 Drug: 270 mg OPC-167832
Once daily oral dose of 270 mg OPC-167832 from Day 1 through Day 14.

Experimental: Stage 2: Low dose OPC-167832/delamanid Drug: Low dose OPC-167832 plus 200 mg delamanid
Once daily oral dose of low dose OPC-167832 plus 200 mg delamanid from Day 1 through Day 14. The OPC-167832 dose will be determined after review of the data from Stage 1.

Experimental: Stage 2: High dose OPC-167832/delamanid Drug: High dose OPC-167832 plus 200 mg delamanid
Once daily oral dose of high dose OPC-167832 plus 200 mg delamanid from Day 1 through Day 14. The OPC-167832 dose will be determined after review of the data from Stage 1.

Active Comparator: Stage 2: delamanid Drug: 200 mg delamanid alone
Once daily oral dose of 200 mg delamanid from Day 1 through Day 14.




Primary Outcome Measures :
  1. Change in TB bacterial load in sputum [ Time Frame: baseline to Day 14 ]
    The change in TB bacterial load in sputum as a measure of early bactericidal activity (EBA) and measured by colony-forming unit (CFU) counts on solid media cultures. The EBA will be measured as the slope of the change in log-CFU from baseline (ie, the mean of the values from Day -2 and Day -1) to Day 14.

  2. Plasma drug levels of OPC-167832 with and without delamanid at specified pre-dose and post-dose time points [ Time Frame: up to Day 14-20 ]
  3. Incidence of adverse events (AEs) [ Time Frame: Up to follow-up visit, an average of 28 days ]
    The incidence of AEs and the incidence of abnormal laboratory findings in clinical laboratory tests (serum chemistry, hematology, urinalysis, and coagulation), physical examinations, vital signs, and electrocardiograms will be assessed.


Secondary Outcome Measures :
  1. Changes in sputum lipoarabinomannan (LAM) concentration and time to detection (TTD) in the Mycobacteria Growth Indicator Tube® (MGIT) system [ Time Frame: baseline to Day 14 ]
    The slope of the change in log-LAM values of OPC-167832 with and without delamanid.

  2. Plasma concentrations of rifampin and isoniazid at specified post-dose time points [ Time Frame: Day 14 ]
  3. Plasma concentrations of DM-6705 at specified pre-dose and post-dose time points [ Time Frame: Day 1, 2, and 14-20 ]
  4. Correlation of corrected interval using Fridericia's method (QTcF) and plasma concentrations of OPC-167832 with and without delamanid [ Time Frame: Day 1 and Day 14 ]
  5. Incidence of AEs of OPC-167832 with delamanid [ Time Frame: Up to follow-up visit, an average of 28 days ]
    Incidence of AEs and the incidence of abnormal laboratory findings in clinical laboratory tests (serum chemistry, hematology, urinalysis, and coagulation), physical examinations, vital signs, and electrocardiograms of OPC-167832 when administered with delamanid (data derived in Stage 2) will be compared with the administration of OPC-167832 alone (data derived from Stage 1).



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written, informed consent prior to initiation of any trial-related procedures, and able, in the opinion of the investigator, to comply with all the requirements of the trial.
  • Male or female participants between 18 and 64 years of age (inclusive) at the screening visit.
  • Body mass index ≥ 16.0 and ≤ 32.0 kg/m^2 (inclusive) at the screening visit.
  • Newly diagnosed, uncomplicated, drug-susceptible pulmonary TB.
  • Microscopy performed on a sputum smear at screening indicates presence of acid-fast bacilli (at least 1+).
  • Able to produce an adequate volume of sputum (approximately 10 mL or more estimated overnight production).
  • Female participants of childbearing potential must agree to use 2 different approved methods of birth control or remain abstinent throughout the participation in the trial and for 12 weeks after the last dose of IMP.
  • Male participants must agree to use 2 different approved methods of birth control or remain abstinent throughout the participation in the trial and for 12 weeks after the last dose of IMP.

Exclusion Criteria:

  • Participants are known or suspected of having resistance to rifampicin, isoniazid, ethambutol, or pyrazinamide using any combination of Xpert MTB/RIF, line probe assay, culture, and/or epidemiologic history at screening.
  • Poor general condition where no delay in treatment can be tolerated or where immediate hospital admission is warranted.
  • Evidence of clinically significant metabolic (including ongoing or current hypokalemia), gastrointestinal, neurological, psychiatric, endocrine or liver (e.g., hepatitis B and C) disease; malignancy; or other abnormalities (other than the indication being studied).
  • History of or current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
  • Known bleeding disorders or family history of bleeding disorders.
  • Any diseases or conditions in which the use of delamanid, rifampicin, isoniazid, pyrazinamide, or ethambutol is contraindicated.
  • Any prior treatment for M. tuberculosis within the past 3 years.
  • Any treatment with a drug active against M. tuberculosis (e.g., quinolones) within the 3 months prior to screening.
  • Clinical evidence of severe extrapulmonary TB (e.g., miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
  • Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB). In particular any underlying condition that could interfere with the assessment of x-ray images, sputum collection, or interpretation of sputum findings, or otherwise compromise the subject's participation in the trial.
  • Any renal impairment characterized by serum creatinine clearance of < 60 mL/min, or hepatic impairment characterized by alanine transaminase, aspartate transaminase, or total bilirubin > 1.5 x upper limit of normal of the clinical laboratory reference range at screening or baseline.
  • Participants who are HIV positive (HIV positive participants may be included in Stage 2 depending on the safety results from Stage 1).
  • Changes in the ECG such as QTcF > 450 msec, atrioventricular block II or III, bi-fasicular block, at screening or baseline or current or history of clinically significant ventricular arrhythmias. Other ECG changes if considered clinically significant by the investigator.
  • Participants receiving any of the prohibited medications within the specified periods or who would be likely to require prohibited concomitant therapy during the trial.
  • Female participants who are breast-feeding or who have a positive pregnancy test result prior to receiving the first dose of IMP or RHEZ on Day 1.
  • History of significant drug and/or alcohol abuse within 2 years prior to screening.
  • History of or current hepatitis or carriers of HBsAg and/or anti-HCV.
  • Positive urine or blood alcohol test and/or urine drug screen for substance abuse at screening.
  • History of having taken an investigational drug within 30 days preceding trial entry.
  • A history of difficulty in donating blood.
  • Donation of blood or plasma within 30 days prior to dosing.
  • Consumption of alcohol and/or grapefruit, grapefruit juice, Seville oranges, or Seville orange juice and related products within 72 hours prior to the first dose of IMP or RHEZ on Day 1.
  • History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
  • Any known prior exposure to OPC-167832 or delamanid.
  • Participants with significant medical comorbidities that in the opinion of the investigator, should not participate in the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03678688


Contacts
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Contact: Global Clinical Development 609 524 6788 mailto:clinicaltransparency@otsuka-us.com

Locations
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South Africa
University of Cape Town (Pty) Ltd. Recruiting
Cape Town, Mowbray, South Africa, 7700
Contact: Prof. Rodney Dawson, MD    +27(0) 21 406 6850    rodney.dawson@uct.ac.za   
TASK Clinical Research Centre Recruiting
Cape Town, South Africa, 7530
Contact: Veronique R de Jager, MD    +27(0) 21 917 1044    dr.veronique@task.org.za   
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Veronique R de Jager, MD TASK Clinical Research Centre
Principal Investigator: Prof. Rodney Dawson, MD University of Cape Town (Pty) Ltd.

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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT03678688     History of Changes
Other Study ID Numbers: 323-201-00003
OPP1178898 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
First Posted: September 20, 2018    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections