Pulmonary TuberculosisPhase 2/3NCT02467608
Efficacy of HUEXC030 in Subjects With Pulmonary Tuberculosis
A Phase 2/3 study testing Isoniazid with HUEXC030 and RZE and HRZE in people with Pulmonary Tuberculosis, run by Orient Pharma Co., Ltd. at 18 sites in Taiwan.
Trial summary
Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Isoniazid with HUEXC030 and RZE and HRZE
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 557 participants
- Where
- 18 sitesTaiwan
- Study dates
- 6 Dec 2012to 9 Jan 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main inclusion criteria:
- A definite case of pulmonary TB
- Patient who is exposed to 3 or less doses of first-line anti-TB drug treatment for current disease.
- Age ≥ 20 years
- Have well documented baseline liver function tests that indicates patient's adequate liver function for enrollment to study.
- AST and ALT < 3x ULN ii. total serum bilirubin < 2.0 mg/dL
Main Exclusion Criteria:
- Have alcoholic liver disease or habitual alcohol consumption > 30 g/day for more than one year
- Previously diagnosed of:
- 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
- Documented history of serious allergic reaction or resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, sugar alcohols or any structurally related compounds
- Subjects who will be using the following therapies after TB treatment starts:
- antiretroviral agents ii. oral corticosteroids
- Subjects are pregnant or lactating
- 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
- Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Taiwan18 sites
Changhua Christian Hospital
Changhua
Changhua Hosiptal Ministry of Health And Welfare
Changhua
Chang Gung Memorial Hospital, ChiaYi
Chiayi City
Chang Gung Memorial Hospital, Kaohsiung
Kaohsiung City
E-DA Hospital, I-Shou University
Kaohsiung City
Kaohsiung Medical University Hospital
Kaohsiung City
Kaohsiung Veterans General Hospital
Kaohsiung City
Chang Gung Memorial Hospital ,Linkou
Linkou District
Taichung Veterans General Hospital
Taichung
Taipei Veterans General Hospital
Taipei, 112
Tri-Service General Hospital
Taipei, 11490
Buddhist Tzu Chi General Hospital
Taipei
Cheng Hsin General Hospital
Taipei
National Taiwan University Hospital
Taipei
Taipei City Hospital
Taipei
Taipei Medical University Hospital
Taipei
Taipei Medical University-Shuang Ho Hospital
Taipei
Taipei Wanfang Hospital
Taipei
About this study
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
Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis
Read the 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.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Isoniazid with HUEXC030 and RZE, HRZE
- Keywords
- HUEXC030, Pulmonary Tuberculosis
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid with HUEXC030 and RZEDrug
Also called INH with HUEXC030, RMP, PZA and EMB
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
HRZEDrug
Also called INH, RMP, PZA and EMB
the same as experimental group,without the excipient of HUEXC030 only
| Study group | Role | What they receive |
|---|---|---|
| Isoniazid with HUEXC030 and RZE | Experimental | 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) Receives: Drug: Isoniazid with HUEXC030 and RZE |
| Isoniazid | Other | 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) Receives: Drug: HRZE |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALT change from baseline to the 8 weeks of study treatment
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.
Measured: 8 weeks
Secondary outcomes (6)
Incidence of ATDH in high risk genotype subjects treated with investigational drugs
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.
Measured: 8 weeks
Incidence of ATDH in high risk genotype subjects treated with investigational drugs
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.
Measured: 26 weeks
Percentage of patients cured by the end of treatment
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.
Measured: 8 weeks
Percentage of patients cured by the end of treatment
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.
Measured: 26 weeks
The overall reduced incidence of ATDH in subjects treated with investigational drugs
Compared to control drugs, the overall reduced incidence of ATDH in all enrolled subjects treated with investigational drugs at study ends.
Measured: 26 weeks
The lowering average level of liver function tests
Compared to control drugs, the lowering average level of liver function tests in all enrolled subjects treated with investigational drugs at study ends.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2015 (estimated)
- Study start6 Dec 2012
- Primary completion9 Jan 2019
- Study completion9 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 557 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orient Pharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Defense Medical Center, Taiwan, National Research Program for Biopharmaceuticals, Taiwan
- Responsible party
- Sponsor
- Investigators
- Yu-Pu Hu, PhD, Study chair, National Defense Medical Center, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02467608
- Sponsor's protocol ID
- NDMC HUEXC030-TB1
- Status last verified
- Jun 2022
- First submitted
- 31 May 2015
- Last updated
- 15 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02467608
- Acronym / sponsor ID
- NDMC HUEXC030-TB1
- Conditions
- Pulmonary Tuberculosis
- Keywords
- HUEXC030, Pulmonary Tuberculosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 557 participants (actual)
- Lead sponsor
- Orient Pharma Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- National Defense Medical Center, Taiwan, National Research Program for Biopharmaceuticals, Taiwan
- Study start
- 6 Dec 2012 (actual)
- Primary completion
- 9 Jan 2019 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 10 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isoniazid with HUEXC030 and RZE | Experimental | Drug: Isoniazid with HUEXC030 and RZESubjects 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) |
| Isoniazid | Other | Drug: HRZESubjects 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) |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoniazid with HUEXC030 and RZEAlso: INH with HUEXC030, RMP, PZA and EMBSubjects 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 | Drug | Isoniazid with HUEXC030 and RZE |
| HRZEAlso: INH, RMP, PZA and EMBthe same as experimental group,without the excipient of HUEXC030 only | Drug | Isoniazid |
Primary outcome
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.
6 secondary outcomes
Incidence of ATDH in high risk genotype subjects treated with investigational drugs
Time frame: 8 weeks
Incidence of ATDH in high risk genotype subjects treated with investigational drugs
Time frame: 26 weeks
Percentage of patients cured by the end of treatment
Time frame: 8 weeks
Percentage of patients cured by the end of treatment
Time frame: 26 weeks
The overall reduced incidence of ATDH in subjects treated with investigational drugs
Time frame: 26 weeks
The lowering average level of liver function tests
Time frame: 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yu-Pu Hu, PhD study chair
National Defense Medical Center, Taiwan
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Isoniazid with HUEXC030 and RZE and HRZE in people with Pulmonary Tuberculosis, run by Orient Pharma Co., Ltd. at 18 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALT change from baseline to the 8 weeks of study treatment (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.