Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of HUEXC030 in Subjects With Pulmonary Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02467608
Recruitment Status : Unknown
Verified March 2016 by Orient Pharma Co., Ltd..
Recruitment status was:  Recruiting
First Posted : June 10, 2015
Last Update Posted : March 4, 2016
Sponsor:
Collaborators:
National Defense Medical Center, Taiwan
National Research Program for Biopharmaceuticals, Taiwan
Information provided by (Responsible Party):
Orient Pharma Co., Ltd.

Brief Summary:
Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis

Condition or disease Intervention/treatment Phase
Pulmonary Tuberculosis Drug: Isoniazid with HUEXC030 and RZE Drug: HRZE Phase 2 Phase 3

Detailed Description:

The study drug is Isoniazid formulated with HUEXC030 as excipient for eradicating ATDH, whereas the reference control is Isoniazid formulated with inactive excipient. Subjects who fulfill all the entry criteria and have written informed consent will be enrolled to the study. Eligible subjects will be randomized in a 1:1 ratio to receive study drug or reference control drug. Subjects will be genotyped according to a selected panel of single nucleotide polymorphisms (SNPs) and categorized into high risk or low risk groups for occurring ATDH via a specific haplotype consists of CYP2E1 and NAT2 SNPs. Based on an extensive study result during 2007 to 2011,the estimated frequency for patients bearing high risk genotypes in Taiwanese population is around 25%. Approximately 352 subjects will be enrolled for genotype screening in order to recruit 88 high risk subjects for each of 44 subjects in the intervention and control arms.

Subjects who are stratified as high risk groups will be administered the test drug or reference control drugs oral daily for 6 months or until treatment completion, i.e. bacteriologically confirmed negative of active M. tuberculosis. Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication under the care of their investigator for at least one follow-up visit at 4 weeks after the End of Study.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 352 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Active Drug Controlled Study to Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Liver Injury in Subjects With Pulmonary Tuberculosis
Study Start Date : December 2012
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis
Drug Information available for: Isoniazid

Arm Intervention/treatment
Experimental: Isoniazid with HUEXC030 and RZE

Subjects who are genotyped as high risk group will be receiving 2 months of intensive treatment comprised of 4 drugs (Isoniazid with HUEXC030 [H], rifampin [R], pyrazinamide [Z] and ethambutol [E]), followed by 4 months of continual chemotherapy consist of Isoniazid, Rifampin (2HRZE/4HR regimen). Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication at least one follow-up visit at 4 weeks after the end of study treatment visit.

Dosage is as below:

Isoniazid with Isoniazid(H):300mg/600mg daily, rifampin [R]: 450~600mg daily, pyrazinamide [Z]; 1000~2000mg daily and ethambutol [E]: 800-1600mg daily)

Drug: Isoniazid with HUEXC030 and RZE
Subjects will receive oral study drug daily in accordance with the following regimen, that is, INH, RMP, PZA, and EMB for the first 2 months followed by INH, RMP and EMB (if medically indicated) daily for 4 additional months
Other Name: INH with HUEXC030, RMP, PZA and EMB

HRZE

Subjects who are genotyped as high risk group will be receiving 2 months of intensive treatment comprised of 4 drugs (Isoniazid [H], rifampin [R], pyrazinamide [Z] and ethambutol [E]), followed by 4 months of continual chemotherapy consist of Isoniazid, Rifampin (2HRZE/4HR regimen). Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication at least one follow-up visit at 4 weeks after the end of study treatment visit.

Dosage is as below:

Isoniazid (H):300mg daily, rifampin [R]: 450~600mg daily, pyrazinamide [Z]; 1000~2000mg daily and ethambutol [E]: 800-1600mg daily)

Drug: HRZE
the same as experimental group,without the excipient of HUEXC030 only
Other Name: INH, RMP, PZA and EMB




Primary Outcome Measures :
  1. ALT change from baseline to the 8 weeks of study treatment [ Time Frame: 8 weeks ]
    The primary efficacy endpoint is the time-interval weighted area under the curve (AUC) of change from baseline in serum ALT, primarily in patients with high risk genotypes. The area under ALT change curve was estimated using the linear trapezoidal rule. The AUC was a measure of cumulative ALT differences from baseline to the 8 weeks of double-blind treatment period.


Secondary Outcome Measures :
  1. Incidence of ATDH in high risk genotype subjects treated with investigational drugs [ Time Frame: 8 weeks ]
    Primarily in patients with high risk genotypes, the lowering incidence of ATDH in subjects treated with anti-TB drugs in combination with HUEXC030 for 8 weeks.

  2. Incidence of ATDH in high risk genotype subjects treated with investigational drugs [ Time Frame: 26 weeks ]
    Primarily in patients with high risk genotypes, the lowering incidence of ATDH in subjects treated with anti-TB drugs in combination with HUEXC030 for 26 weeks or at treatment completion.

  3. Percentage of patients cured by the end of treatment [ Time Frame: 8 weeks ]
    At 8 weeks, the investigational product is not inferior in effectiveness of TB treatment to the control drug, primarily in patients with high risk genotypes.

  4. Percentage of patients cured by the end of treatment [ Time Frame: 26 weeks ]
    At 26 weeks or at treatment completion, the investigational product is not inferior in effectiveness of TB treatment to the control drug, primarily in patients with high risk genotypes.

  5. The overall reduced incidence of ATDH in subjects treated with investigational drugs [ Time Frame: 26 weeks ]
    Compared to control drugs, the overall reduced incidence of ATDH in all enrolled subjects treated with investigational drugs at study ends.

  6. The lowering average level of liver function tests [ Time Frame: 26 weeks ]
    Compared to control drugs, the lowering average level of liver function tests in all enrolled subjects treated with investigational drugs at study ends.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main inclusion criteria:

  1. A definite case of pulmonary TB
  2. Patient who is exposed to 3 or less doses of first-line anti-TB drug treatment for current disease.
  3. Age ≥ 20 years
  4. Have well documented baseline liver function tests that indicates patient's adequate liver function for enrollment to study.

    i. AST and ALT < 3x ULN ii. total serum bilirubin < 2.0 mg/dL

Main Exclusion Criteria:

  1. Have alcoholic liver disease or habitual alcohol consumption > 30 g/day for more than one year
  2. Previously diagnosed of:

    i. extra-pulmonary TB without concomitant lung invasion ii. HIV iii. liver malignancy iv. liver cirrhosis v. any other systemic diseases that may cause liver dysfunction

  3. Documented history of serious allergic reaction or resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, sugar alcohols or any structurally related compounds
  4. Subjects who will be using the following therapies after TB treatment starts:

    i. antiretroviral agents ii. oral corticosteroids

  5. Subjects are pregnant or lactating
  6. Subjects with child-bearing potential who are not committed to take reliable contraception during the participation of the study and at least 4 weeks after the end of the study treatment
  7. Subjects with any other serious disease considered by the investigator not in the condition to enter into 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): NCT02467608


Contacts
Layout table for location contacts
Contact: I-Chan Lee, MS +886-2-2325-7621 ext 2928 ichan.lee@oppharma.com
Contact: Cheng-Huei Hsiong, PhD +886-2-8792-3100 ext 18845 chhsiong@ndmctsgh.edu.tw

Locations
Layout table for location information
Taiwan
Changhua Christian Hospital Recruiting
Changhua, Taiwan
Contact: Ching-Hsiung Lin, MD PhD         
Changhua Hosiptal Ministry of Health And Welfare Recruiting
Changhua, Taiwan
Contact: Yi-Wen Huang, MD PhD         
Chang Gung Memorial Hospital, ChiaYi Recruiting
ChiaYi, Taiwan
Contact: Meng-Jer Hsieh, MD         
Chang Gung Memorial Hospital, Kaohsiung Recruiting
Kaohsiung, Taiwan
Contact: Wen-Feng Fang, MD         
E-DA Hospital, I-Shou University Recruiting
Kaohsiung, Taiwan
Contact: Chun-Kai Huang, MD         
Kaohsiung Medical University Hospital Recruiting
Kaohsiung, Taiwan
Contact: Inn-Wen Chong, MD         
Kaohsiung Veterans General Hospital Recruiting
Kaohsiung, Taiwan
Contact: Susan Shin-Jung Lee, MD         
Chang Gung Memorial Hospital ,Linkou Recruiting
Linkou, Taiwan
Contact: Shih-Wei Lin, MD         
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan
Contact: Wei-Chang Huang, MD         
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan, 112
Contact: Wei-Jhen Su, MD         
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 11490
Contact: Wann-Cherng Perng, MD PhD         
Buddhist Tzu Chi General Hospital Recruiting
Taipei, Taiwan
Contact: Yao-Kuang Wu, MD         
Cheng Hsin General Hospital Recruiting
Taipei, Taiwan
Contact: Wei-Teing Chen, MD PhD         
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Contact: Jann-Yuan Wang, MD PhD         
Taipei City Hospital Terminated
Taipei, Taiwan
Taipei Medical University Hospital Recruiting
Taipei, Taiwan
Contact: Chi-Li Chung, MD PhD         
Taipei Medical University-Shuang Ho Hospital Recruiting
Taipei, Taiwan
Contact: Chun-Nin Lee, MD         
Taipei Wanfang Hospital Recruiting
Taipei, Taiwan
Contact: Ming-Chih Yu, MD         
Sponsors and Collaborators
Orient Pharma Co., Ltd.
National Defense Medical Center, Taiwan
National Research Program for Biopharmaceuticals, Taiwan
Investigators
Layout table for investigator information
Study Chair: Yu-Pu Hu, PhD National Defense Medical Center, Taiwan

Layout table for additonal information
Responsible Party: Orient Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT02467608     History of Changes
Other Study ID Numbers: NDMC HUEXC030-TB1
First Posted: June 10, 2015    Key Record Dates
Last Update Posted: March 4, 2016
Last Verified: March 2016

Keywords provided by Orient Pharma Co., Ltd.:
HUEXC030
Pulmonary Tuberculosis

Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Isoniazid
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents