NCT02467608

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
557

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2012

Longer than P75 for phase_2

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 6, 2012

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

May 31, 2015

Completed
10 days until next milestone

First Posted

Study publicly available on registry

June 10, 2015

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 9, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 9, 2019

Completed
Last Updated

June 15, 2022

Status Verified

June 1, 2022

Enrollment Period

6.1 years

First QC Date

May 31, 2015

Last Update Submit

June 14, 2022

Conditions

Keywords

HUEXC030Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Incidence of ATDH in high risk genotype subjects treated with investigational drugs

    8 weeks

  • Incidence of ATDH in high risk genotype subjects treated with investigational drugs

    26 weeks

  • Percentage of patients cured by the end of treatment

    8 weeks

  • Percentage of patients cured by the end of treatment

    26 weeks

  • The overall reduced incidence of ATDH in subjects treated with investigational drugs

    26 weeks

  • +1 more secondary outcomes

Study Arms (2)

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)

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)

Drug: HRZE

Interventions

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

Also known as: INH with HUEXC030, RMP, PZA and EMB
Isoniazid with HUEXC030 and RZE
HRZEDRUG

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

Also known as: INH, RMP, PZA and EMB
Isoniazid

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Have alcoholic liver disease or habitual alcohol consumption \> 30 g/day for more than one year
  • 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
  • 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:
  • i. 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Changhua Christian Hospital

Changhua, Taiwan

Location

Changhua Hosiptal Ministry of Health And Welfare

Changhua, Taiwan

Location

Chang Gung Memorial Hospital, ChiaYi

Chiayi City, Taiwan

Location

Chang Gung Memorial Hospital, Kaohsiung

Kaohsiung City, Taiwan

Location

E-DA Hospital, I-Shou University

Kaohsiung City, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, Taiwan

Location

Chang Gung Memorial Hospital ,Linkou

Linkou District, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Buddhist Tzu Chi General Hospital

Taipei, Taiwan

Location

Cheng Hsin General Hospital

Taipei, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei City Hospital

Taipei, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Taipei Medical University-Shuang Ho Hospital

Taipei, Taiwan

Location

Taipei Wanfang Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

IsoniazidNSC 366140

Condition Hierarchy (Ancestors)

TuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

HydrazinesOrganic ChemicalsIsonicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Yu-Pu Hu, PhD

    National Defense Medical Center, Taiwan

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2015

First Posted

June 10, 2015

Study Start

December 6, 2012

Primary Completion

January 9, 2019

Study Completion

January 9, 2019

Last Updated

June 15, 2022

Record last verified: 2022-06

Locations