Efficacy of HUEXC030 in Subjects With Pulmonary Tuberculosis

Pulmonary Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02467608
• Other study ID #: NDMC HUEXC030-TB1
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 6, 2012
• Est. completion date: January 9, 2019

Study information

• Verified date: June 2022
• Source: Orient Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 557
• Est. completion date: January 9, 2019
• Est. primary completion date: January 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pulmonary Tuberculosis
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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
• HRZE
the same as experimental group,without the excipient of HUEXC030 only

Locations

Country	Name	City	State
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Changhua Hosiptal Ministry of Health And Welfare	Changhua
Taiwan	Chang Gung Memorial Hospital, ChiaYi	Chiayi City
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung
Taiwan	E-DA Hospital, I-Shou University	Kaohsiung
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital ,Linkou	Linkou
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Buddhist Tzu Chi General Hospital	Taipei
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei City Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Medical University-Shuang Ho Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Taipei Wanfang Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
Orient Pharma Co., Ltd.	National Defense Medical Center, Taiwan, National Research Program for Biopharmaceuticals, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	8 weeks
Secondary	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.	8 weeks
Secondary	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.	26 weeks
Secondary	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.	8 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks