Efficacy of HUEXC030 in Subjects With Pulmonary Tuberculosis

Orient Pharma

Status and phase: Completed; Phase 3; Phase 2

Conditions: Pulmonary Tuberculosis

Treatments: Drug: Isoniazid with HUEXC030 and RZE; Drug: HRZE

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02467608

NDMC HUEXC030-TB1

Details and patient eligibility

About

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

Full 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.

Enrollment: 557 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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557 participants in 2 patient groups

Isoniazid with HUEXC030 and RZE

Experimental group

Description:

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)

Treatment:

Drug: Isoniazid with HUEXC030 and RZE

Isoniazid

Other group

Description:

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)

Treatment:

Drug: HRZE