Clinical Trials for Tuberculosis in India_Soumya Swaminathan

7/28/2019 Clinical Trials for Tuberculosis in India_Soumya Swaminathan

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Clinical Trials for TB in IndiaSoumya Swaminathan MD,

National Institute for Research in TB (formerly TuberculosisResearch Centre), Chennai


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Tuberculosis in India

Accounts for > 25% of global TB burden

2 million new cases, 1.5 million in RNTCP

~ 1000 deaths/day

~ 60% adults latently infected with M.tuberculosis ~ 100,000 MDRTB cases each year

90,000 notified pediatric cased (7% of total)

Major risk factors

Undernutrition HIV

Diabetes mellitus

Smoking, indoor air pollution


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INH Resistance and MDRTB inNew and Re-treatment Cases

MDR (global)

New: 3.7%, Retreatment: 20%

Relapse: 32%

Failure: 49%

Treatment after default: 32%

In India, among new TB cases, INHresistance 11-17%, MDRTB 2-3%

Among re-treatment cases, INHresistance 25-40% and MDRTB 15-20%


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Clinical Trials for TB in India

New drugs/regimens for drug sensitiveand drug resistant TB

HIV+ and HIV- patients

Immunomodulators/supplementary agents

Trials to predict/reduce toxicity

Mostly conducted in public hospitalsaffiliated to academic centres/medicalcolleges or research organizations


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Format of Trial Description

Aim, type of trial

Nature of Intervention

Primary, secondary outcome measure/s

Period, sample size

Site/s

Sponsor

Information obtained from NIH clinical trialsregistry and Clinical Trials Registry of India


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End Points for TB Clinical Trials

Phase II: early bactericidal activity and extended EBA 2nd month culture conversion and speed of

culture conversion

Safety Phase III

Cure at end of treatment (bacteriologic)

Recurrence (bacteriologic) Death usually low in HIV negative patients

Development of drug resistance esp Rifampin

Radiographic changes unreliable


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Phase III trials for new TB therapy

Recognised endpoints in Phase III trials: Failure: Culture positive in the last 2 mo of treatment

Death: except accidental deaths

Recurrences: ~80% occur within 12 months of stoppingtreatment. Genotyping of strains important to

distinguish true relapse (re-activation) from re-infection

Endpoint rare (5%-10%) leading to trials involving a large

number of participants

> 5 years for a phase III trial from conception to

presentation of results.


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TRC Study 18Ofloxacin in the intensive phase

1 2 3 4 5 6

INH

RIF

PZA

EMB

OFX

PZA

RIFINH

Intensive phase Continuation phase

months


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The authors should be congratulated for their efforts to

further shorten chemotherapy for TB.,. The paper

convincingly shows that adding a quinolone to the initial

intensive phase of therapy permits the regimen to beshortened to 4 or 5 months with no loss in efficacy and no

important increase in toxicity. I have no important

reservations or suggestions regarding the study design or its

results. However, it would be of interest to the world tomention the added cost of ofloxacin . The ICMR has

contributed greatly to our understanding of TB. It is good

to know that the tradition continues.

EDITORIAL OFFICESThe New England Journal of Medicine


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Response at end of treatment(360 patients with drug susceptible TB)

Ind J Tub 2002: 49: 27-38

92% 94% 96% 97%

1% 1%1%

1%


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Regimen Patients Relapse

No (%)

Time of relapse aftertreatment (in months)

1-6 7-12 > 12

O3 83 7 (8%) 5 1 1

O4 81 3 (4%) 3 0 0

O5 86 2 (2%) 2 0 0

O4 (2) 91 12 (13%) 9 3 0

Relapse after treatment (up to 24 months)(341 patients with drug susceptible TB)

Ind J Tub 2002: 49: 27-38


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Efficacy and Tolerability of 3- and 4- monthregimens containing Moxifloxacin in sputum

smear and culture positive pulmonary TB

Randomized, parallel group, multiple arm, openlabel trial (phase III)

Intervention: 4 regimens containing Moxifloxacin

Outcomes: Relapse (24 months aftercompletion of treatment), sputum cultureconversion at 2nd month, bacteriologic response

at end of treatment, adverse reactions Period: 2007-2015, sample size 1650

Site and sponsor: Tuberculosis ResearchCentre, ICMR


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RegimensRegimen Months Month

s1 2 3 4 5 6

Test Reg1

RHZEM 3

Test Reg2

RHZEM RHM 4

Test Reg

3

RHZEM RHM3 4

Test Reg4

RHZEM RHEM3 4

Control RHZE3 RH3 6

R

Rifampicin 450/ 600 mgH Isoniazid 300/ 600 mgZ Pyrazinamide 1500 mg

E Ethambutol 800/ 1200 mgM Moxifloxacin 400 mg


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Moxifloxacin 3 and 4-month regimens: 2-mosputum culture conversion

P 0.001P 0.06


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High Dose Isoniazid Adjuvant therapy forMulti Drug Resistant TB

Randomized double blind placebo control, parallelassignment safety/efficacy study

Intervention: INH high (16-18mg/kg/day) and regulardose (5mg/kg/day) vs placebo in addition to

standardized MDR regimen (kanamycin, levofloxacin,protionamide, cycloserine, PAS)

Outcome: Time to sputum culture conversion,radiological improvement, proportion with peripheralneuropathy, hepatotoxicity

Period: 2004-2007, SS 134

Sites: Kanpur and Nagpur, India

Sponsor: GSVM Medical college, Kanpur


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Antibacterial activity, safety and tolerabilityof TMC207 in patients with MDRTB

Randomized double blind parallel assignment safety/efficacy study(Phase II)

2 stages: exploratory (I) and proof of effectiveness (II)

Intervention: TMC 207 400mg QD for 14 days, 200mg tiw for 6 or 22weeks vs placebo, in addition to background regimen (national

guideline) Outcome: time to sputum culture conversion (8 weeks) and 24

weeks. Pharmacokinetics of TMC 207 and its metabolite M2 inplasma and sputum, PK/PD relationships for activity andsafety/efficacy, drug interactions with other drugs in backgroundregimen. Patients will be followed for 96 wks

Period: 2007-2012. Sample size 50 for I stage and 150 for stage II Sites: Multicentric (south Africa, Thailand, Brazil, India, Latvia, Peru,

Philippines, Russia)

Sponsor: Tibotec Virco Virology

STREAM T i l Th E l ti f


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STREAM Trial: The Evaluation of aStandardised Treatment Regimen of Anti-

Tuberculosis Drugs for Patients with MDR-TB Based on short Bangladesh regimen tried under

operational/program conditions

4 countries: Ethiopia, India, S Africa, Vietnam

Test regimen: moxifloxacin, clofazimine, ethambutol and

pyrazinamide given for nine months (40 weeks),supplemented by kanamycin, isoniazid andprothionamide in the first four months (16 weeks). Totalmax length: 48 weeks

Control regimen: Locally used WHO-approved MDRTBtreatment regimen

Primary Outcomes: proportion of patients with afavourable outcome at 27 months and proportion of

patients experiencing Grade III or IV AE


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Efficacy of 6- vs 9-month intermittent shortcourse ATT in HIV-infected TB patients

Randomized open label Phase III trial

Patients with HIV and pulmonary/extrapulmonary TB randomized to receive

2EHRZ3/4RH3 or 2EHRZ3/7RH3 ART naive

Outcome: cure, relapse rate at 24 months

Period: 2001-2008, SS 300 Site: Tuberculosis Research Centre, Chennai

Sponsor: Indian Council of Medical Research


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Am J Respir Crit Care Med 2010; 181:743-51

300 patients, ART-nave, 70% PTB, medianCD4 count 150

Cure rate and mortality no different

Recurrences (bacteriologic) significantly lower

with 9-month regimen

All 19 patients developed acquired Rifampicinresistance at time of failure

Am J Respir Crit Care Med 2010; 181:743-51


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Baseline and recurrence cultures fingerprintedusing IS6110, MIRU-VNTR and spoligotyping

20 paired HIV+ and 25 HIV- TB patientspecimens

Re-activation accounted for 92% of HIV-

Re-infection accounted for 88% of HIV+recurrences

J Infect Dis 2010; 201:691-703


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Comparing Daily vs intermittentATT in HIV with Pulmonary TB

Efficacy of 3 different regimens in reducing failures andemergence of acquired rifampicin resistance in HIV/TB

Randomized, open label, parallel arm

Regimens: 2EHRZ7/4RH7, 2EHRZ7/4RH3 2EHRZ3/4RH3(control)

ART as per national guidelines

Outcomes: bacteriologic failure, ARR during treatmentperiod

2009-2015, sample size: 420 Site: Tuberculosis Research Centre, Chennai

Sponsor: USAID through WHO


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Objectives: To identify clinical and laboratory predictors

of tuberculosis-associated IRIS (TB-IRIS) To study the immunopathogenesis of TB-IRIS

among HIV-infected patients initiating anti-TBand anti-retroviral trt

NIH Intramural-to-India Program/US-India JWG

Collaborators: Tuberculosis Research Centre, Chennai, India(Soumya Swaminathan, G Narendran, Subhash Babu)

NIH/NIAID/LIR & LPD, Bethesda, Maryland (Brian Porter, IriniSereti, Alan Sher)

Predictors and Immunologic Characterizationof TB-associated IRIS in a cohort of HIV-

infected TB patients in Chennai


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Safety and Efficacy of two different once-daily antiretroviral treatment regimens along

with anti-TB treatment

Randomized, open label, active control, parallelassignment safety/efficacy trial

Interventions: ddI/3TC/NVP vs ddI/3TC/EFV

along with standard intermittent TB regimen,from 2nd month of ATT Outcome: virological suppression at 6

months, adverse events, death, TBcure/relapse

2006-2009, sample size 180 Site: Tuberculosis Research centre clinics at

Chennai, Madurai and Vellore, Tamil Nadu Sponsor: National AIDS Control Organization


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Intent to Treat Analysis at 24 weeks(Swaminathan et al Clinical Infectious Diseases 2011;53:716724)

Response to ART EfavirenzregimenN = 59

NevirapineregimenN = 57

Favourable response(viral load < 400 copies/ml)

50 (85%)p=0.038

38 (67%)

Unfavourable responses 9 19

failure 6 11death - 5

Lost to f/u 3 3

RR of failure with NVP 1.28 (95% CI 1.03-1.6)

Effi f Si th 36 th i f


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Efficacy of a Six-month vs a 36-month regimen forprevention of tuberculosis in HIV-infected persons in

India: A Randomized Clinical Trial Randomized, open label clinical trial

Interventions: 6EH vs 36H

Endpoint: development of TB, death, AE

Period: 2001-2008 Site: Tuberculosis Research centre clinics at

Chennai, Madurai

Sponsor: USAID through WHO

In press Plos One


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Results

712 patients randomized, 2/3rds female, medianCD4 count 350

TB Incidence rate (2.4 and 1.5/100 py) muchlower than historical 6.9/100py both regimens

highly efficacious in preventing TB No significant difference between 6EH and 36H

in efficacy or safety

TB and death rates 3-4 times higher inCD4


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TB Incidence Rate

6EH 36H

ITT (n= 683)rate/100 py (95%

CI)

2.44(1.42 3.46)

1.55( 0.73 2.36)

Per Protocol(n =619)

2.03(1.1 3.0)

1.3(0.5 - 2.1)

Rate Ratio 1.54 (95% CI 0.72 3.25)


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TB Incidence by Immune StatusWithin each CD4 stratum, rates not different

by regimen


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Cost-Effectiveness Results

Strategy

Lifeexpectancy

(years) Costs ($)

Cost-effectivenessratio ($/YLS)

Selectivereferral

16.85 95 --

Currentstandard

16.86 110 660

Routinereferral

16.88 120 730

India per capita GDP: $1,015 Pho, M et al, PLoS One.2012;7(4):e36001. Epub 2012 Apr 30.


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Early vs Delayed initiation of ART for IndianHIV-Infected individuals with TB on ATT

Randomized, open label trial 150 HIV+ TB+ randomized to

receive ART (d4T / ZDV + 3TC +

EFV) after

2-4 or 8-12 weeks of starting ATT

Primary end points: death from

any cause & progression of HIV

disease

No difference in mortality in

groups Incidence of ART failure was 31% in

delayed versus 16% in early ART

arm (p = 0.045)

KM - Disease progression free

survival

At 79%, significantly better for theearly ART group, as against 64% for

delayed ART group (p = 005)

Sinha et al, BMC Infectious Diseases 2012, 12:168 doi:10.1186/1471-2334-12-168


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Immediate versus delayed start of anti-HIVtherapy in HIV-infected TB patients with CD4< 250cells/mm3 (ACTG 5221) N Engl J Med 2011;365:1482-91.

Immediate (within 2 weeks) ART compared to deferredART (after 8 weeks) of ATT in reducing death and AIDS-defining illness

Randomized, open label, active control, parallelassignment, safety/efficacy study TDF/FTC/EFV orally once daily within 2 weeks or at 8-

12 weeks of ATT in patients with CD4 < 200 cells/mm

Outcome: proportion of patients surviving without AIDS

progression at week 48 Period: 2006-2013, SS 800

Site: multicentric, 22 sites globally. YRG Care, Chennai

Sponsor: NIAID, NIH


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Results (ACTG 5221)

809 patients, median CD4 77 12.9% of early ART group and 16% of delayed

group had AIDS-defining event or death within48 weeks, ns

Among patients with CD4< 50, 15.5% vs 27%developed new illness or died, p=0.02

TB IRIS more common with early (11%)

compared to deferred ART (5%) Virological suppression at 48 weeks same

(~75%)


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Other ACTG/HPTN studies at YRG

Care, Chennai or NARI, Pune

HPTN 052: Can TB and other OIs beprevented by starting ART early?

ACTG 5253: Diagnostic algorithm for TBusing new tools

ACTG 5274: Empiric TB treatment in HIV+patients with CD4< 50

GSK TB vaccine in HIV+ subjects: safetyand immunogenecity


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Efficacy of Thrice weekly DOTS in HIV-associated tuberculosis

Non-randomized open label active controlparallel assignment efficacy study

Efficacy of thrice-weekly intermittent shortcourse anti-TB chemotherapy in TB patients

with and without HIV 2EHRZ3/4RH3 in HIV+ and HIV- patients Outcome: cure rate, treatment failure, death,

relapse, adverse drug reactions

Period: 2006-2009, SS 150 Site and Sponsor: All India Institute of Medical

Sciences, New Delhi and Ministry of health Study completed, manuscript submitted

Effi d S f t f I d l t


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Efficacy and Safety of Immunomodulatoras an Adjunct Therapy in New Pulmonary

TB (Cat I) Patients Randomized double blind placebo controlled

safety/efficacy study (Phase III)

6 doses ofMycobacterium indicus pranii0.1 ml(100 million bacilli) intradermal

Time of sputum conversion and cure rate,relapses and clinical adverse events

Period: 2007-2009, sample size 300

Multicentric Sponsor: Dept of Biotechnology, Govt of India

Data under analysis

Efficac and Safet of Imm nomod lator


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Efficacy and Safety of Immunomodulatoras an Adjunct Therapy in Pulmonary TB

Retreatment Patients Randomized double blind placebo controlled

safety/efficacy study (Phase III)

6 doses ofMycobacterium indicus praniiinimproving sputum conversion and cure rate,reducing relapses and safety issues in Cat IIpatients


Multicentric: Delhi, Tamil Nadu, Rajasthan,Andhra Pradesh

Sponsor: Dept of Biotechnology, Govt of India

Data under analysis

Efficacy of Oral Zinc Administration as


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Efficacy of Oral Zinc Administration asan Adjunct Therapy in New Pulmonary

TB (Cat I) Patients

Randomized double blind placebo controlledparallel assignment efficacy trial

Role of oral zinc (50mg/day) along with ATT

among newly diagnosed pulm TB pts 2008-2009, sample size 150

Time of smear conversion, cure rate, relapses,

adverse reactions and immunological changes Site: AIIMS, New Delhi

Sponsor: Ministry of Science and Technology


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Pulmonary TB and vitamin D

Randomized double blind placebo controlled efficacystudy (phase III) Role of oral vit D as adjunct therapy in Cat I pulmonary

TB along with assessment of immunological parameters Cholecalciferol 60,000IU weekly for 2 months, then

monthly, with 1 gm calcium carbonate daily Placebo lactose Time to convert sputum positivity to negativity, effector

immune function, safety, relapses


Site: AIIMS, New Delhi Sponsors: Dept Biotechnology, Indian Council of

Medical Research


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Effect of Addition of Vit D to ConventionalTreatment in New Pulmonary TB Patients

Randomized, double blind placebo control,parallel assignment safety/efficacy study

100,000 IU cholecalciferol once every 2 weeksfor 2 months, in addition to ATT

Time to sputum culture conversion, treatmentoutcomes (RNTCP), weight gain, performancestatus, % smear/culture positive at 8 weeks,time to growth in liquid media

2009-2011 (not recruiting yet), SS 250 Site: Christian Medical College, Vellore Sponsor: CMC and Dalhousie Univ, Canada


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Micronutrient Supplementation inPediatric Pulmonary TB

Randomized double blind factorial assignment(Phase III)

Intervention: zinc 20mg/day, multimineral 2RDA, multimineral+zinc, placebo with std ATT in

pediatric (6mo-15 yrs) new pulmonary TB Outcome: change in z score for weight,

improvement in x-Ray, IFN-gamma activity at 2and 6 months, symptoms

Period: 2008-2011, SS 400 Site: All India Institute of Medical Sciences Sponsor: AIIMS, Univ of Bergen


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Immunomodulatory effects of Withaniasomnifera (Ashwagandha) in pulmonary TB

Proof of concept prospective, randomized,parallel arm, placebo controlled clinical trial toevaluate the effect of PHP-TB in patients withpulmonary TB (phase II)

Intervention: Capsule PHP-TB containing hydro-alcoholic extracts of Withania somnifera 300mgonce daily or placebo for entire 6 months of ATT(2EHRZ3/4RH3)

Outcomes: weight gain, improved QOL, sputumAFB clearance, xRay and immune parameters

Period: 2008-2009, SS 120 Site and Sponsor: Govt Medical College,

Jammu


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Role of N-acetyl cysteine in patients withnewly detected sputum positive pulm TB

Randomized, parallel group placebo controlledtrial

Intervention: N-acetyl cysteine 600mg once

daily vs placebo, along with standard ATT Outcome: sputum smear conversion rate (1, 2,

4, 6 month), cure and relapse rates

Period: 2007-2009, SS 60

Site and sponsor: Christian Medical College,Vellore


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Early Prediction of anti-tuberculosistreatment induced hepatitis

Hepatitis most common side effect with short-courseATT, mortality 6-12% if drugs continued

Onset 3-135 days, usually within 3 months

Pathogenesis and dose relationship not clear (?value ofTDM)

Case control, prospective study

To evaluate plasma levels of hepatotoxic drugs (INH,Rif, PZA plus significant metabolites) among patients on

ATT and compare levels among those who develop drug

induced hepatitis on follow up and those who do not Cat I and II patients will be enrolled and followed

Outcome: plasma levels of INH, Rif and PZA amongcases and controls, metabolites

Period: 2007-2009, SS 100

Site and Sponsor: All India Institute of Medical Sciences,

ff f


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Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced

hepatotoxicity in an in vitro modelHum Exp Toxicol. 2012 Aug;31(8):788-97

Aim: to investigate the role of curcumin (CUR), silymarin(SILY) and N-acetylcysteine (N-ACET) on hepatotoxicityby ATT drugs using an in vitro model of human

hepatocellular carcinoma cell line (HepG2) Results: (a) increased cell viability, (b) healthy-looking

cell morphology as revealed by phase contrastmicroscopy, (c) active respiring cells as observed with

confocal microscopy upon staining with a mitochondrialmembrane-specific dye, MitoTracker() Red, andreduction in the sub-G(1) peak in cell cycle analysis byflow cytometry

Clinical trials needed


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Hum Exp Toxicol. 2012 Aug;31(8):788-97.doi: 10.1177/0960327111433901. Epub2012 Feb 8.

Singh M, Sasi P, Gupta VH, Rai G,Amarapurkar DN, Wangikar PP.

Source

Department of Chemical Engineering,Indian Institute of Technology Bombay,Powai, Mumbai, Maharashtra, India.


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Study of NAT2 and Cyp2E1 gene as riskfactors for hepatitis

Prospective Study of N-acetyltransferase 2 (NAT2) geneand Rifampicin induced cytochrome p4502E1 (Cyp2E1)gene as susceptibility risk factors for anti-tuberculosisdrug induced hepatitis

Slow acetylator genotype of NAT2 and wild typegenotype of Cyp2E1 associated with greater toxicity

Design: Case control, prospective

Intervention: Newly diagnosed pulmonary TB patientsenrolled, genotyped and followed

Period: 2005-2008 (completed)

Site and sponsor: Maulana Azad Medical College, NDelhi


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Efficacy and Safety of Modified Anti-tubercular Regimens in TreatmentofTuberculosis in Patients With Underlying Compensated and

Decompensated Chronic Liver Disease

This study is not yet open for participant recruitment. Verified August 2012 by Institute of Liver and Biliary Sciences, India

Sponsor: Institute of Liver and Biliary Sciences, India

ClinicalTrials.gov Identifier: NCT01677871

Study Type Interventional

Study Phase Study Design Allocation: RandomizedEndpoint Classification: Safety/Efficacy StudyIntervention Model: Parallel AssignmentMasking: Open LabelPrimary Purpose: Treatment

Condition Chronic Liver Disease With Tuberclosis

Intervention

Drug: 2HRZE/4HRIsoniazid + Rifampicin+Pyrazinamide+Ethambutol for initial 2 months followed byIsoniazid + Rifampicin for next 4 months

Drug: 2HRLE/4HRIsoniazid + Rifampicin+ Levofloxacin+Ethambutol for initial 2 months followed byIsonizid + Rifampicin for next 4 months

Drug: 9HLEIsoniazid+ Levofloxacin+ Ethambutol for 9 months

Drug: 9RLERifampicin + Levofloxacin+ Ethambutol for 9 months

Study Arm (s)

Experimental: 2HRZE/4HRIsoniazid + Rifampicin+Pyrazinamide+Ethambutol for initial 2 monthsfloolowed by Isoniazid + Rifampicin for next 4 monthsIntervention: Drug: 2HRLE/4HR

Active Comparator: 2HRLE/4HRIsoniazid + Rifampicin+ Levofloxacin+Ethambutol for initial 2 monthsfollowed by Isonizid + Rifampicin for next 4 monthsIntervention: Drug: 2HRZE/4HR

Experimental: 9HLEIsoniazid+ Levofloxacin+ Ethambutol for 9 monthsIntervention: Drug: 9RLE

Active Comparator: 9RLERifampicin + Levofloxacin+ Ethambutol for 9 monthsIntervention: Drug: 9HLE

Safety and Efficacy of different regimens of re


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Safety and Efficacy of different regimens of re-introduction of anti-TB drugs in anti-TB drug

induced liver damage

Randomized open label, dose comparison, parallelassignment safety/efficacy study

At time of re-introduction of anti-TB drugs, patientsrandomized to i) daily INH, Rif, PZA full dose ii) Rif day

1, INH day 8, PZA day 15 full dose iii) graduallyincreasing doses of INH day 1, Rif day 8 and PZA day15

Safety, predictors and risk factors for recurrence

Liver functions monitored weekly

Period: 2006-2008

Sites: Tirupati, AP and New Delhi

Sponsor: All India Institute of Medical Sciences, N Delhi

ff f f


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Effect of parasitic worm infections onthe immune response to TB bacteria

To determine if pre-existing intestinal helminth infectionor filarial infection alters the immune response tomycobacterial antigens or clinical expression of TB

Randomized clinical trial

TST positive persons randomized to receiveDEC+Albendazole or placebo

Outcome: Change in TST status, cellular immunologicalchanges

Period: 2002-2009, SS 5200 Site: Tuberculosis Research centre, Chengleput district

Sponsor: NIAID, NIH

Early bactericidal activity and pharmacokinetic


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Early bactericidal activity and pharmacokineticstudy of LL 3858 among newly diagnosed

sputum smear positive pulmonary TB patients

Phase IIa open label single arm study to determine EBA,extended EBA and pharmacokinetics of novelcompound LL 3858 of Lupin Ltd

Intervention: LL3858 400 mg OD orally for 5 days. 16 hr

collection of sputum on day 1,3,4,6 Patients will receive full ATT from day 7

Outcome: Safety, fall in log10 colony forming units(CFU) of M.tuberculosis/ml sputum 0-2 days (EBA) and2-5 days (extended EBA), PK profile full profile after 1st

and 5th

dose and a sample on days 7 and 8 Sample size: 40 (20 analyzable) Period: 2009 (not yet recruiting)

Sponsor: Lupin Ltd


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Gaps and Challenges

Low capacity for Phase I and II (EBA), PK studies Limited capacity for high quality phase III trials of

new drugs/diagnostics/vaccines

Few well characterized patient/ population

cohorts No biological specimen repository from well

characterized TB patients

Limited research on pediatric TB

No national network of centres that can undertakemulticentric trials

Few studies combining clinical and immunologic/

pathogenesis research (network of basic and


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Research Priorities

Efficient and cost-effective point of carediagnostic test for TB (all forms)

Shorter treatment regimens for drug-susceptible and drug resistant TB

Trials of new and repurposed drugs for TB

Adjunct treatment with agents that

improve drug efficacy/tolerability Pharmacokinetics of first and second line

anti-TB drugs in adults and children

Documents

Clinical Trials for Tuberculosis in India_Soumya Swaminathan