Clinical trial NCT02467608: Efficacy of HUEXC030 in Subjects With Pulmonary Tuberculosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Tuberculosis
Keywords: HUEXC030
Pulmonary Tuberculosis
Lead sponsor: Orient Pharma Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: National Defense Medical Center, Taiwan
name: National Research Program for Biopharmaceuticals, Taiwan
First posted: 2015-06-10
Enrollment: 557
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: ALT change from baseline to the 8 weeks of study treatment
timeFrame: 8 weeks
Secondary outcomes:
measure: Incidence of ATDH in high risk genotype subjects treated with investigational drugs
timeFrame: 8 weeks
measure: Incidence of ATDH in high risk genotype subjects treated with investigational drugs
timeFrame: 26 weeks
measure: Percentage of patients cured by the end of treatment
timeFrame: 8 weeks
measure: Percentage of patients cured by the end of treatment
timeFrame: 26 weeks
measure: The overall reduced incidence of ATDH in subjects treated with investigational drugs
timeFrame: 26 weeks
measure: The lowering average level of liver function tests
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Changhua
country: Taiwan
facility: Changhua Hosiptal Ministry of Health And Welfare
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital, ChiaYi
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung
city: Kaohsiung
country: Taiwan
facility: E-DA Hospital, I-Shou University
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital ,Linkou
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei City Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University-Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Taipei Wanfang Hospital
Study officials:
affiliation: National Defense Medical Center, Taiwan
name: Yu-Pu Hu, PhD
role: STUDY_CHAIR
References: