REMoxTB: Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis
Sponsor
Global Alliance for TB Drug Development (Other)
Overall Status
Completed
CT.gov ID
NCT00864383
Collaborator
European and Developing Countries Clinical Trials Partnership (EDCTP) (Other), University College, London (Other), Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma (Industry), Sanofi (Industry)
1,931
47
3
73
41.1
0.6
Study Details
Study Description
Brief Summary
REMoxTB is a study for the "Rapid Evaluation of Moxifloxacin in the treatment of sputum smear positive tuberculosis". REMoxTB aims to find and evaluate new drugs and regimens that shorten the duration of tuberculosis therapy.
The purpose of REMoxTB is to evaluate the efficacy, safety and acceptability of two moxifloxacin-containing treatment combinations to determine whether substituting ethambutol with moxifloxacin in one combination, and/or substituting isoniazid with moxifloxacin in another combination, makes it possible to reduce the duration of treatment for TB.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The current recommended treatments for tuberculosis (TB) require a patient to take multiple drugs for six to eight months. Because the course of therapy is long, many patients do not adhere to treatment and as a consequence they have a poor outcome. In these cases either the sputum is not cleared of the bacteria causing tuberculosis, or the disease returns again (called relapse). Response to medication can be monitored during treatment by collecting regular sputum samples and examining these samples by culture, for the organisms that cause tuberculosis.
The commonly used drugs to treat tuberculosis are rifampicin, isoniazid, ethambutol and pyrazinamide. Previous studies in animals and in humans suggest that a new drug called moxifloxacin may also be an effective treatment in tuberculosis. Moreover, promising laboratory studies on mice suggest that moxifloxacin may enable the total duration of chemotherapy to be reduced to four months, which would be a significant improvement for patients taking medication for tuberculosis.
This study will involve comparisons that are designed to assess whether substituting moxifloxacin for individual drugs in existing treatment combinations will enable tuberculosis treatment to be shortened. Patients selected for the study will be allocated to one of three treatment groups. The first group will be given six months standard treatment. A second group will receive moxifloxacin substituted for ethambutol, as part of a four month regimen, to see whether the shorter treatment is not inferior to the standard six month treatment. The third group will receive moxifloxacin substituted for isoniazid, as part of a four month regimen, to see whether the shorter treatment is not inferior to the standard six month treatment.
Hypotheses:
-
In treatment-naïve adults with active pulmonary TB treated with eight weeks of moxifloxacin (M), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (i.e. a standard regimen where moxifloxacin is substituted for ethambutol (E)), followed by nine weeks of moxifloxacin, isoniazid and rifampicin, followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin) (Comparison 1).
-
In treatment-naïve adults with active pulmonary TB treated with eight weeks of ethambutol, moxifloxacin, rifampicin and pyrazinamide (i.e. a standard regimen where moxifloxacin is substituted for isoniazid), followed by nine weeks of moxifloxacin and rifampicin followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin) (Comparison 2).
Study Design
Study Type:
Interventional
Actual Enrollment
:
1931 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
Oct 1, 2013
Actual Study Completion Date
:
Feb 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Regimen 1 - 2EHRZ/4HR (control regimen) Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. |
Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg
All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Other Names:
|
| Experimental: Regimen 2 - 2MHRZ/2MHR Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. |
Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg
All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Other Names:
|
| Experimental: Regimen 3 - 2EMRZ/2MR Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo |
Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg
All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ). [18 months (within one year of completion of therapy)]
The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results.
- Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting) [18 months (within one year of completion of therapy)]
The number of participants includes all patients who had at least one grade 3 or 4 adverse event.
Secondary Outcome Measures
- Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT). [18 months (within one year of completion of therapy)]
The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis.
- Number of Patients Who Are Culture Negative (Solid LJ Culture) [8 weeks]
Number of patients who are TB LJ culture negative at 8 weeks.
- Number of Patients Who Are Culture Negative (Liquid MGIT Culture) [8 weeks]
Number of patients who are TB MGIT culture negative at 8 weeks.
- Time to First Culture Negative Sputum Sample (LJ Solid Media) [18 months]
Culture negative for TB using LJ cultures.
- Time to First Culture Negative Sputum Sample (MGIT Liquid Media) [18 months]
- Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media. [18 months]
Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.
- Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media. [18 months]
Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity.
-
Two sputum specimens positive for tubercle bacilli on smear microscopy at least one of which must be processed and positive at the study laboratory.
-
Aged 18 years or over.
-
No previous anti-tuberculosis chemotherapy.
-
A firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during the treatment and follow-up period.
-
Agreement to participate in the study and to give a sample of blood for HIV testing (see appendices 1 & 2).
-
Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an IUCD in place.
-
Laboratory parameters performed up to 14 days before enrolment.
-
Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal.
-
Serum total bilirubin level less than 2.5 times upper limit of normal. Creatinine clearance (CrCl) level greater than 30 mls/min.
-
Haemoglobin level of at least 7.0 g/dL.
-
Platelet count of at least 50x109cells/L.
-
Serum potassium greater than 3.5 mmol/L.
-
Negative pregnancy test (women of childbearing potential).
Exclusion Criteria:
-
Unable to take oral medication.
-
Previously enrolled in this study.
-
Received any investigational drug in the past 3 months.
-
Received an antibiotic active against M. tuberculosis in the last 14 days (fluoroquinolones, macrolides, standard anti-tuberculosis drugs).
-
Any condition that may prove fatal during the first two months of the study period.
-
TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome
-
Pre-existing non-tuberculosis disease e.g. diabetes, liver or kidney disease, blood disorders,peripheral neuritis, chronic diarrhoeal disease in which the current clinical condition of the patient is likely to prejudice the response to, or assessment of treatment.
-
Pregnant or breast feeding.
-
Suffering from a condition likely to lead to uncooperative behaviour e.g. psychiatric illness or alcoholism.
-
Contraindications to any medications in the study regimens.
-
Known to have congenital or sporadic syndromes of QTc prolongation or receiving concomitant medication reported to increase the QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).
-
Known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated with quinolones.
-
Patients already receiving anti-retroviral therapy.
-
Patients whose initial isolate is shown to be multiple drug resistant (i.e. resistant to rifampicin and isoniazid) or monoresistant to rifampicin, or resistant to any fluoroquinolone)
-
Weight less than 35kg
-
HIV infection with CD4 count less than 250 cells/µL.
-
End stage liver failure (class Child-Pugh C).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tuberculosis and Thoracic Tumor Research Institute | Beijing | China | 101149 | |
| 2 | Shanghai Pulmonary Hospital | Shanghai | China | 200433 | |
| 3 | TB Institute | Tianjin | China | 300041 | |
| 4 | Nirmal Kumar Jain | Jaipur | Rajasthan | India | |
| 5 | Mahatma Gandhi Medical College& Hospital | Jaipur | Rajsthan | India | |
| 6 | Ram-Tej Hospital, | Agra | Uttar Pradesh | India | |
| 7 | Siddharth Nursing Home, | Agra | Uttar pradesh | India | |
| 8 | Rajul Nursing Home | Aligarh | Uttar Pradesh | India | |
| 9 | Varshneya Chest Clinic & Eye Care Centre | Aligarh | Uttar Pradesh | India | |
| 10 | Dr. Neeraj Gupta Clinic | Firozabad | Uttar Pradesh | India | |
| 11 | S.P.S Chauhan Clinic | Firozabad | Uttar Pradesh | India | |
| 12 | Dr. R. K. Garg's Clinic, | Gaziabad | Uttar Pradesh | India | 2011002 |
| 13 | Indra Nursing Home and Maternity Centre | Ghaziabad | Uttar Pradesh | India | |
| 14 | Dr. AK Singh Clinic | Kanpur | Uttar Pradesh | India | |
| 15 | Dr. S. K. Katiyar, Swaroop Nagar, | Kanpur | Uttar Pradesh | India | |
| 16 | Guru Tej Bahadur Hospital | Kanpur | Uttar Pradesh | India | |
| 17 | Dr. Komal Gupta | Lucknow | Uttar Pradesh | India | |
| 18 | New City Hospital and Trauma Centre, | Lucknow | Uttar Pradesh | India | |
| 19 | Surya Chest Foundation, | Lucknow | Uttar Pradesh | India | |
| 20 | Surya Kant Clinic | Lucknow | Uttar Pradesh | India | |
| 21 | Dr. Mahip Saluja Clinic, U.P. | Meerut, | Uttar Pradesh | India | |
| 22 | Arya Chest Clinic, UP,India | Meerut | Uttar Pradesh | India | |
| 23 | Dr. S. P. Sondhi Clinic, | Meerut | Uttar Pradesh | India | |
| 24 | Sri Ram Plaza | Meerut | Uttar Pradesh | India | |
| 25 | Jigyasa Medical Center | Moradabad | Uttar Pradesh | India | |
| 26 | Saanvi MultiSpeciality Clinic, | Moradabad | Uttar Pradesh | India | |
| 27 | A-One Hospital | Delhi | India | 110087 | |
| 28 | Dr. D.K. Chauhan | New Delhi | India | 110002 | |
| 29 | Centre for advanced lung and sleep disorders | New Delhi | India | 110026 | |
| 30 | Dr. Mittal's clinic | New Delhi | India | 110043 | |
| 31 | Diligent Hospital | New Delhi | India | 110062 | |
| 32 | Ish Medical Centre and Respiratory Lab, | New Delhi | India | ||
| 33 | Smt Prakash Devi Memorial Medical Centre, | New Delhi | India | ||
| 34 | Centre for Respiratory Disease Research at KEMRI | Nairobi | Kenya | ||
| 35 | Institute of Respiratory Medicine (IPR) Jalan Pahang | Kuala Lumpur | Malaysia | 53000 | |
| 36 | Hospital General de Occidente de la secretaria | Guadalajara | Seattle | Mexico | 45170 |
| 37 | Madibeng centre for Research, 40 Pienaar Street, | Madibeng | Brits | South Africa | 0250 |
| 38 | Clinical HIV Research Unit (CHRU) | Johannesburg | Westdene | South Africa | 2092 |
| 39 | Centre for TB Research and Innovation, University of Cape Town Lung Institute | Cape Town | South Africa | 7700 | |
| 40 | Tiervlei Trial Center and University of Stellenbosch | Cape Town | South Africa | ||
| 41 | Unit for Clinical & Biomedical TB Research, MRC Durban | Durban | South Africa | ||
| 42 | NIMR Mbeya Medical Research Programme | Mbeya | Tanzania | ||
| 43 | Kilimanjaro Christian Medical Centre | Moshi | Tanzania | ||
| 44 | Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University | Khon Kaen | Mueang | Thailand | 40200 |
| 45 | Chest Disease Institute (CDI), Ministry of Public, | Nonthaburi | Mueang | Thailand | 11000 |
| 46 | Rajavithi Hospital, Division Of Pulmonary Medicine | Bangkok | Phayathai | Thailand | 10400 |
| 47 | University Teaching Hospital | Lusaka | Zambia |
Sponsors and Collaborators
- Global Alliance for TB Drug Development
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- University College, London
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Sanofi
Investigators
- Study Director: Stephen H Gillespie, MB BCh BAO MD DSc, University of St Andrews
- Principal Investigator: Andrew Nunn, BSc MSc, MRC Clinical Trials Unit
- Principal Investigator: Sarah K Meredith, MB BS MSc, MRC Clinical Trials Unit
- Principal Investigator: Timothy D McHugh, BSc PhD CSi, Centre for Medical Microbiology, Royal Free and University College Medical School
- Principal Investigator: Ali Zumla, BSc MBChB MSc PhD, Centre for International Health, Royal Free and University College Medical School
- Principal Investigator: Alexander Pym, MB BMRCP PhD, Unit for Clinical & Biomedical TB Research, MRC Durban
- Principal Investigator: Peter Mwaba, MB ChB MMed PhD, University Teaching Hospital
- Principal Investigator: Noel Sam, MMed MD, Kilimanjaro Christian Medical Centre
- Principal Investigator: Andreas Diacon, BM MD, Tiervlei Trial Center and University of Stellenbosch
- Principal Investigator: Rodney Dawson, MB ChB FCP, Centre for TB Research and Innovation, UCT Lung Institute
- Principal Investigator: Evans Amukoye, MBChB. Mmed (Paediatric), Centre for Respiratory Disease Research at KEMRI
- Principal Investigator: Leonard Maboko, MD MSc PhD, NIMR - Mbeya Medical Research Programme
- Principal Investigator: Ian Sanne, MBBCH FCP(SA), Clinical HIV Research Unit (CHRU), Westdene
- Principal Investigator: Cheryl Louw, MBChB, Madibeng Centre For Research, Brits
- Principal Investigator: Mengqui Gao, MD, Beijing Tuberculosis and Thoracic Tumor Research Institute
- Principal Investigator: Qing Zhang, MD, Shanghai Pulmonary Hospital, Shanghai, China
- Principal Investigator: Xiexiu Wang, MD, TB Institute, Tianjin
- Principal Investigator: Aziah Mahayiddin, MD, Institute of Respiratory Medicine (IPR) Jalan Pahang, Malaysia
- Principal Investigator: Watchara Boonsawat, MD PhD, Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
- Principal Investigator: Charoen Chuchottaworn, MD, Chest Disease Institute (CDI), Ministry of Public Health, Nonthaburi
- Principal Investigator: Pairaj Kateruttanakul, MD, Rajavithi Hospital, Division of Pulmonary, Department of Medicine, Bangkok
- Principal Investigator: Gerardo Amaya-Tapia, MD, Hospital General de occidente de la secretaria, Seattle, Mexico
- Principal Investigator: Stephen Murray, M.D, PhD, Global Alliance for TB Drug Development
- Principal Investigator: Michael Brown, BA, BM, BCh, MRCP, PhD, DTM&H, London School of Hygiene and Tropical Medicine
- Principal Investigator: Rakesh Lal, MD, Centre for Advanced Lung and Sleep Disorders, New Delhi, India
- Principal Investigator: Rakesh Mittal, MBBS MD, Dr. Mittal's Clinic, Balaji Medical Store, New Delhi, India
- Principal Investigator: A K Jain, MBBS FICA, Diligent Hospital, New Delhi, India
- Principal Investigator: Mahesh Kapoor, MBBS DTCD, A One Hospital, New Delhi, India
- Principal Investigator: D K Chauhan, MBBS, Dr D.K. Chauhan, New Delhi, India
- Principal Investigator: Mahip Saluja, M.D, Dr. Mahip Saluja Clinic, Meerut, U.P. India
- Principal Investigator: Neeraj Gupta, MD, Dr. Neeraj Gupta, Firozabad ,U.P, India
- Principal Investigator: Subodh Katiyar, MD, Dr Subodh, Swaroop Nagar,Kanpur, India
- Principal Investigator: Nirmal K Jain, MD, Dr.Nirmal Kumar Jain, Jaipur, India
- Principal Investigator: Komal Gupta, M.D, Kilkari , Lucknow , India
- Principal Investigator: Fahad Khan, MD, New City Hospital and Trauma Centre, Lucknow, India
- Principal Investigator: Vaibhav Gupta, MD, Saanvi MultiSpeciality Clinic, Moradabad, UP, India,
- Principal Investigator: Suraj P Sondhi, MD, Dr. S. P. Sondhi Clinic , Meerut U.P India
- Principal Investigator: Siddharth Agarwal, MD, Siddharth Nursing Home, Agra, U.P India
- Principal Investigator: Sanjay Teotia, M.D, Dr. Sanjay Teotia Clinic, Meerut, U.P , India
- Principal Investigator: S PS Chauhan, MD, Dr. SPS Chauhan, Firozabad, U.P-India,
- Principal Investigator: Mahesh Mishra, MD, Mahatma Gandhi Medical College& Hospital , Jaipur, India
- Principal Investigator: Ashish Rohatgi, DTCD, Ish Medical Centre and Respiratory Lab, New Delhi- India
- Principal Investigator: Om P Rai, MD, Guru Tej Bahadur Hospital, Kanpur India
- Principal Investigator: Pawan Varshneya, MD, Varshneya Chest Clinic & Eye Care Centre, Aligarh, UP India
- Principal Investigator: R K Garg, MD, Dr. R. K. Garg's Clinic, U.P, India
- Principal Investigator: Vinod K Karhana, M.D, Prakash Devi Memorial Medical Centre,New Delhi, India
- Principal Investigator: Vijay K Khurana, M.D, Ram-Tej Hospital, Agra, India
- Principal Investigator: Surya Kant, MD, FCCP, FNCP, FCAI, Dr.Surya Kant, Lucknow, India
- Principal Investigator: Shalini Arya, MD, Arya Chest Clinic, Meerut, UP,India
- Principal Investigator: Ashok K Singh, MD, FCCP, FCCS, Pulmonary Care and Sleep Clinic, Kanpur, India
- Principal Investigator: Bhanu P Singh, MD, FCCP, Surya Chest Foundation, Lucknow India
- Principal Investigator: Chandra P Singh, MD, Jigyasa Medical Center,Uttar Pradesh, India
- Principal Investigator: Arun Aggarwal, MD, Indra Nursing Home and Maternity Centre, Uttar Pradesh, India
- Principal Investigator: Anjula Bhargava, MS, Rajul Nursing Home, Sasni Gate, Aligarh, UP India
- Principal Investigator: Angela Crook, MRC Clinical Trials Unit
- Principal Investigator: Salome Charalambous, The Aurum Institute, Tembisa Hospital, South Africa
- Principal Investigator: Lerato Mohapi, Soweto Perinatal HIV Research Unit, Johannesburg, South Africa
- Principal Investigator: Nesri Padayatchi, Caprisa eThakwini Research Facility, Durban, South Africa
- Principal Investigator: Sandy Pillay, International Clinical Trials Unit, Durban, South Africa
Study Documents (Full-Text)
None provided.More Information
Publications
- Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, Pym A, Mahayiddin AA, Chuchottaworn C, Sanne IM, Louw C, Boeree MJ, Hoelscher M, McHugh TD, Bateson AL, Hunt RD, Mwaigwisya S, Wright L, Gillespie SH, Bentley SD. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med. 2013 Dec;1(10):786-92. doi: 10.1016/S2213-2600(13)70231-5. Epub 2013 Nov 21.
- Friedrich SO, Rachow A, Saathoff E, Singh K, Mangu CD, Dawson R, Phillips PP, Venter A, Bateson A, Boehme CC, Heinrich N, Hunt RD, Boeree MJ, Zumla A, McHugh TD, Gillespie SH, Diacon AH, Hoelscher M; Pan African Consortium for the Evaluation of Anti-tuberculosis Antibiotics (PanACEA). Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment. Lancet Respir Med. 2013 Aug;1(6):462-70. doi: 10.1016/S2213-2600(13)70119-X. Epub 2013 Jul 1.
Responsible Party:
Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier:
NCT00864383
Other Study ID Numbers:
- REMoxTB
- ISRCTN85595810
First Posted:
Mar 18, 2009
Last Update Posted:
Mar 21, 2017
Last Verified:
Feb 1, 2017
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Period Title: Per- Protocol | |||
| STARTED | 640 | 655 | 636 |
| COMPLETED | 510 | 514 | 524 |
| NOT COMPLETED | 130 | 141 | 112 |
| Period Title: Per- Protocol | |||
| STARTED | 640 | 655 | 636 |
| COMPLETED | 555 | 568 | 551 |
| NOT COMPLETED | 85 | 87 | 85 |
Baseline Characteristics
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR (Isoniazid) | Regimen 3 - 2EMRZ/2MR (Ethambutol) | Total |
|---|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Total of all reporting groups |
| Overall Participants | 510 | 514 | 524 | 1548 |
| Age, Customized (participants) [Number] | ||||
| < 25 years |
160
31.4%
|
162
31.5%
|
146
27.9%
|
468
30.2%
|
| 25-35 years |
145
28.4%
|
162
31.5%
|
175
33.4%
|
482
31.1%
|
| > 35 years |
205
40.2%
|
190
37%
|
203
38.7%
|
598
38.6%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
154
30.2%
|
163
31.7%
|
155
29.6%
|
472
30.5%
|
| Male |
356
69.8%
|
351
68.3%
|
369
70.4%
|
1076
69.5%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| Black |
238
46.7%
|
210
40.9%
|
237
45.2%
|
685
44.3%
|
| Asian |
160
31.4%
|
154
30%
|
161
30.7%
|
475
30.7%
|
| Mixed race |
111
21.8%
|
148
28.8%
|
126
24%
|
385
24.9%
|
| Other |
1
0.2%
|
2
0.4%
|
0
0%
|
3
0.2%
|
| Weight group (participants) [Number] | ||||
| < 40 kg |
50
9.8%
|
44
8.6%
|
58
11.1%
|
152
9.8%
|
| 40-45 kg |
80
15.7%
|
90
17.5%
|
82
15.6%
|
252
16.3%
|
| > 45-55 kg |
206
40.4%
|
210
40.9%
|
204
38.9%
|
620
40.1%
|
| > 55-75 kg |
161
31.6%
|
158
30.7%
|
174
33.2%
|
493
31.8%
|
| > 75 kg |
13
2.5%
|
12
2.3%
|
6
1.1%
|
31
2%
|
| Smoking status (participants) [Number] | ||||
| Never |
246
48.2%
|
231
44.9%
|
230
43.9%
|
707
45.7%
|
| Past |
119
23.3%
|
111
21.6%
|
134
25.6%
|
364
23.5%
|
| Current |
145
28.4%
|
172
33.5%
|
160
30.5%
|
477
30.8%
|
| HIV positivity (participants) [Number] | ||||
| Number [participants] |
38
7.5%
|
37
7.2%
|
35
6.7%
|
110
7.1%
|
| Drug resistance (participants) [Number] | ||||
| Isoniazid |
29
5.7%
|
34
6.6%
|
39
7.4%
|
102
6.6%
|
| Pyrazinamide |
14
2.7%
|
7
1.4%
|
6
1.1%
|
27
1.7%
|
| Cavitation (participants) [Number] | ||||
| Number [participants] |
368
72.2%
|
357
69.5%
|
367
70%
|
1092
70.5%
|
| Time to positivity on MGIT sputum culture (participants) [Number] | ||||
| ≥ 5 days |
266
52.2%
|
263
51.2%
|
258
49.2%
|
787
50.8%
|
| < 5 days |
229
44.9%
|
239
46.5%
|
254
48.5%
|
722
46.6%
|
| Not available |
15
2.9%
|
12
2.3%
|
12
2.3%
|
39
2.5%
|
Outcome Measures
| Title | Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ). |
|---|---|
| Description | The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results. |
| Time Frame | 18 months (within one year of completion of therapy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 510 | 514 | 524 |
| Number [participants with failure or relapse] |
43
8.4%
|
78
15.2%
|
105
20%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Regimen 1 - 2EHRZ/4HR (Control Regimen), Regimen 2 - 2MHRZ/2MHR |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was defined as a between-group difference of less than 6 percentage points in the upper boundary of the two-sided 97.5% Wald confidence interval for the difference in proportion of patients with an unfavorable outcome. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in proportions |
| Estimated Value | 6.1 | |
| Confidence Interval |
(2-Sided) 97.5% 1.7 to 10.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted difference from control in proportion of unfavorable outcome - percentage points | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Regimen 1 - 2EHRZ/4HR (Control Regimen), Regimen 3 - 2EMRZ/2MR |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Noninferiority was defined as a between-group difference of less than 6 percentage points in the upper boundary of the two-sided 97.5% Wald confidence interval for the proportion of patients with an unfavorable outcome. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference from control |
| Estimated Value | 11.4 | |
| Confidence Interval |
(2-Sided) 97.5% 6.7 to 16.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted difference from control in rate of unfavorable outcome- percentage points | |
| Title | Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting) |
|---|---|
| Description | The number of participants includes all patients who had at least one grade 3 or 4 adverse event. |
| Time Frame | 18 months (within one year of completion of therapy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population, defined as all subjects who underwent randomization and who received at least on dose of study drug. |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 639 | 655 | 636 |
| Number [participants with Grade 3 or 4 AEs] |
123
24.1%
|
127
24.7%
|
111
21.2%
|
| Title | Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT). |
|---|---|
| Description | The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. |
| Time Frame | 18 months (within one year of completion of therapy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 498 | 498 | 512 |
| Number [participants with failure or relapse] |
65
12.7%
|
98
19.1%
|
131
25%
|
| Title | Number of Patients Who Are Culture Negative (Solid LJ Culture) |
|---|---|
| Description | Number of patients who are TB LJ culture negative at 8 weeks. |
| Time Frame | 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 422 | 457 | 458 |
| Number [participants who are culture negative] |
352
69%
|
394
76.7%
|
401
76.5%
|
| Title | Number of Patients Who Are Culture Negative (Liquid MGIT Culture) |
|---|---|
| Description | Number of patients who are TB MGIT culture negative at 8 weeks. |
| Time Frame | 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 419 | 440 | 429 |
| Number [participants who are culture negative] |
235
46.1%
|
274
53.3%
|
260
49.6%
|
| Title | Time to First Culture Negative Sputum Sample (LJ Solid Media) |
|---|---|
| Description | Culture negative for TB using LJ cultures. |
| Time Frame | 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients excluding late screen failures |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 600 | 617 | 604 |
| Median (95% Confidence Interval) [Time to culture negative status / weeks] |
6.0
|
6.0
|
6.0
|
| Title | Time to First Culture Negative Sputum Sample (MGIT Liquid Media) |
|---|---|
| Description | |
| Time Frame | 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients excluding late screen failures |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 600 | 617 | 604 |
| Median (95% Confidence Interval) [Time to culture negative status / weeks] |
11.9
|
8.0
|
8.0
|
| Title | Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media. |
|---|---|
| Description | Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results. |
| Time Frame | 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects. |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 640 | 655 | 636 |
| Number [participants with unfavorable outcome] |
172
33.7%
|
219
42.6%
|
217
41.4%
|
| Title | Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media. |
|---|---|
| Description | Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results. |
| Time Frame | 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR |
|---|---|---|---|
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. |
| Measure Participants | 640 | 655 | 636 |
| Number [participants with unfavorable outcome] |
87
17.1%
|
132
25.7%
|
132
25.2%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class. | |||||
| Arm/Group Title | Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR | |||
| Arm/Group Description | Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm. | |||
All Cause Mortality |
||||||
| Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/639 (5.9%) | 46/655 (7%) | 40/636 (6.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal Distension | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Abdominal Mass | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Abdominal Pain | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Abdominal Pain Lower | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Abdominal Tenderness | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Acute Abdomen | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Ascites | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Diarrhoea | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Gastrointestinal Disorder | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Haematemesis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Haematochezia | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nausea | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 2 |
| Pancreatitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Peptic Ulcer Perforation | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Vomiting | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 6/636 (0.9%) | 11 |
| Infections and infestations | ||||||
| Appendicitis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Diarrhoea Infectious | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Disseminated Tuberculosis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Gangrene | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hepatitis B | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Investigations | ||||||
| Aspartate Aminotransferase Increased | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Blood Bilirubin Increased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Blood Creatinine Increased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Breath Sounds Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Gamma- Glutamyltransferase Increased | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Haemoglobin Decreased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hepatic Enzyme Increased | 3/639 (0.5%) | 3 | 3/655 (0.5%) | 3 | 4/636 (0.6%) | 4 |
| International Normalised Ratio Increased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Liver Function Test Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Prothrombin Time prolonged | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Respiratory Rate Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Weight Decreased | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asphyxia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Asthma | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Bronchospasm | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Cough | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Dysphonia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Dyspnoea | 5/639 (0.8%) | 6 | 2/655 (0.3%) | 2 | 6/636 (0.9%) | 8 |
| Haemoptysis | 7/639 (1.1%) | 8 | 6/655 (0.9%) | 7 | 2/636 (0.3%) | 2 |
| Haemothorax | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hydropneumothorax | 0/639 (0%) | 0 | 1/655 (0.2%) | 3 | 0/636 (0%) | 0 |
| Hypoventilation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Oropharyngeal Pain | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pleural Effusion | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Pneumonia Aspiration | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pneumothorax | 2/639 (0.3%) | 5 | 3/655 (0.5%) | 3 | 3/636 (0.5%) | 6 |
| Rales | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Respiratory Distress | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Respiratory Failure | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Rhonchi | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Wheezing | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Regimen 1 - 2EHRZ/4HR (Control Regimen) | Regimen 2 - 2MHRZ/2MHR | Regimen 3 - 2EMRZ/2MR | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 507/639 (79.3%) | 537/655 (82%) | 522/636 (82.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Abdominal Lymphadenopathy | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Anaemia | 10/639 (1.6%) | 17 | 13/655 (2%) | 16 | 8/636 (1.3%) | 11 |
| Hypochromic Anaemia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Iron Deficiency Anaemia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Leukocytosis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Leukopenia | 8/639 (1.3%) | 13 | 9/655 (1.4%) | 12 | 9/636 (1.4%) | 12 |
| Lymph Node Pain | 2/639 (0.3%) | 7 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Lymphadenitis | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Lymphadenopathy | 43/639 (6.7%) | 61 | 44/655 (6.7%) | 71 | 50/636 (7.9%) | 68 |
| Lymphopenia | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Microcytic Anaemia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Monocytosis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Neutropenia | 4/639 (0.6%) | 13 | 3/655 (0.5%) | 6 | 2/636 (0.3%) | 5 |
| Neutrophilia | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Splenomegaly | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Thrombocytopenia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Thrombocytosis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Cardiac disorders | ||||||
| Arrhythmia | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Bradycardia | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Cardiac Failure | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Cardiac Failure Congestive | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Congestive Cardiomyopathy | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Cor Pulmonale | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hyperdynamic Left Ventricle | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Left Ventricular Hypertrophy | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Palpitations | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 5 | 2/636 (0.3%) | 6 |
| Pericardial Disease | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Sinus Tachycardia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tachyarrhythmia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Tachycardia | 40/639 (6.3%) | 54 | 48/655 (7.3%) | 71 | 39/636 (6.1%) | 45 |
| Ventricular Hypertrophy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Ear and labyrinth disorders | ||||||
| Auricular Swelling | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Cerumen Impaction | 10/639 (1.6%) | 13 | 5/655 (0.8%) | 7 | 8/636 (1.3%) | 8 |
| Deafness | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Ear Canal Erythema | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Ear Discomfort | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 2 |
| Ear Pain | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 4 | 5/636 (0.8%) | 7 |
| Ear Pruritus | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Haematotympanum | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hearing Impaired | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hypoacusis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 2 |
| Otorrhoea | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tinnitus | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Tympanic Membrane Hyperaemia | 0/639 (0%) | 0 | 4/655 (0.6%) | 4 | 1/636 (0.2%) | 1 |
| Tympanic Membrane Perforation | 2/639 (0.3%) | 4 | 4/655 (0.6%) | 4 | 3/636 (0.5%) | 4 |
| Tympanic Membrane Scarring | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Tympanosclerosis | 1/639 (0.2%) | 2 | 4/655 (0.6%) | 6 | 1/636 (0.2%) | 2 |
| Vertigo | 2/639 (0.3%) | 2 | 3/655 (0.5%) | 3 | 0/636 (0%) | 0 |
| Eye disorders | ||||||
| Astigmatism | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Cataract | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 4/636 (0.6%) | 4 |
| Conjunctival Haemorrhage | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Conjunctival Hyperaemia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Conjunctival Irritation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Conjunctival Pallor | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 3/636 (0.5%) | 3 |
| Conjunctivitis | 2/639 (0.3%) | 2 | 4/655 (0.6%) | 6 | 3/636 (0.5%) | 3 |
| Conjunctivitis Allergic | 3/639 (0.5%) | 3 | 2/655 (0.3%) | 2 | 3/636 (0.5%) | 3 |
| Corneal Opacity | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Dry Eye | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Eye Irritation | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 2 |
| Eye Oedema | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Eye Pain | 4/639 (0.6%) | 4 | 2/655 (0.3%) | 2 | 4/636 (0.6%) | 4 |
| Eye Pruritus | 4/639 (0.6%) | 4 | 5/655 (0.8%) | 6 | 8/636 (1.3%) | 9 |
| Eyelid Oedema | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Eyelids Pruritus | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hypermetropia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Keratitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Lacrimation Increased | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Night Blindness | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Ocular Discomfort | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Ocular Hyperaemia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Ocular Icterus | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Photophobia | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Pterygium | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Scleral Hyperaemia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Scleritis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Uveitis | 0/639 (0%) | 0 | 1/655 (0.2%) | 3 | 0/636 (0%) | 0 |
| Vision Blurred | 10/639 (1.6%) | 12 | 8/655 (1.2%) | 8 | 9/636 (1.4%) | 9 |
| Visual Acuity Reduced | 7/639 (1.1%) | 9 | 16/655 (2.4%) | 18 | 12/636 (1.9%) | 12 |
| Visual Impairment | 4/639 (0.6%) | 5 | 3/655 (0.5%) | 3 | 1/636 (0.2%) | 2 |
| Vitreous Floaters | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal Discomfort | 1/639 (0.2%) | 1 | 5/655 (0.8%) | 6 | 7/636 (1.1%) | 8 |
| Abdominal Distension | 3/639 (0.5%) | 3 | 2/655 (0.3%) | 3 | 4/636 (0.6%) | 4 |
| Abdominal Pain | 12/639 (1.9%) | 17 | 15/655 (2.3%) | 20 | 15/636 (2.4%) | 17 |
| Abdominal Pain Lower | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Abdominal Pain Upper | 10/639 (1.6%) | 10 | 14/655 (2.1%) | 14 | 7/636 (1.1%) | 8 |
| Abdominal Rigidity | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Abdominal Tenderness | 5/639 (0.8%) | 5 | 9/655 (1.4%) | 13 | 6/636 (0.9%) | 8 |
| Anal Haemorrhage | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Anal Pruritus | 1/639 (0.2%) | 2 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Ascites | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Chapped Lips | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Cheilitis | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Colitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Constipation | 10/639 (1.6%) | 11 | 12/655 (1.8%) | 17 | 3/636 (0.5%) | 3 |
| Dental Caries | 6/639 (0.9%) | 6 | 1/655 (0.2%) | 1 | 7/636 (1.1%) | 9 |
| Diarrhoea | 16/639 (2.5%) | 18 | 38/655 (5.8%) | 51 | 46/636 (7.2%) | 59 |
| Dyspepsia | 10/639 (1.6%) | 13 | 8/655 (1.2%) | 8 | 5/636 (0.8%) | 6 |
| Dysphagia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Epigastric Discomfort | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Faecal Volume Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Flatulence | 0/639 (0%) | 0 | 1/655 (0.2%) | 3 | 0/636 (0%) | 0 |
| Food Poisoning | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Frequent Bowel Movements | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Gastritis | 4/639 (0.6%) | 5 | 7/655 (1.1%) | 7 | 3/636 (0.5%) | 4 |
| Gastrointestinal Hypermotility | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Gastrointestinal Pain | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Gastrointestinal Sounds Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Gastrooesophageal Reflux Disease | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Gingival Pain | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Gingival Recession | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Glossitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Haematemesis | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Haematochezia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Haemorrhoidal Haemorrhage | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Haemorrhoids | 3/639 (0.5%) | 4 | 1/655 (0.2%) | 1 | 3/636 (0.5%) | 3 |
| Hyperchlorhydria | 3/639 (0.5%) | 3 | 3/655 (0.5%) | 3 | 0/636 (0%) | 0 |
| Lip Blister | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Lip Swelling | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Lip Ulceration | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Lower Gastrointestinal Haemorrhage | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Melaena | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Mouth Haemorrhage | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Nausea | 40/639 (6.3%) | 49 | 39/655 (6%) | 44 | 45/636 (7.1%) | 50 |
| Odynophagia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Oesophagitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Oral Mucosal Discolouration | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Oral Pain | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Paraesthesia Oral | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Parotid Gland Enlargement | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Peptic Ulcer | 2/639 (0.3%) | 3 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Post-Tussive Vomiting | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 5 | 1/636 (0.2%) | 2 |
| Rectal Discharge | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Rectal Haemorrhage | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Rectal Tenesmus | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Salivary Gland Disorder | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Salivary Gland Pain | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Tongue Coated | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tongue Disorder | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Tongue Haemorrhage | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tongue Ulceration | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Toothache | 5/639 (0.8%) | 7 | 5/655 (0.8%) | 6 | 4/636 (0.6%) | 4 |
| Vomiting | 44/639 (6.9%) | 56 | 70/655 (10.7%) | 95 | 70/636 (11%) | 92 |
| General disorders | ||||||
| Adhesion | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Asthenia | 12/639 (1.9%) | 14 | 10/655 (1.5%) | 11 | 16/636 (2.5%) | 19 |
| Catheter Site Pain | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Chest Discomfort | 2/639 (0.3%) | 2 | 4/655 (0.6%) | 4 | 1/636 (0.2%) | 1 |
| Chest Pain | 60/639 (9.4%) | 76 | 49/655 (7.5%) | 57 | 55/636 (8.6%) | 68 |
| Chills | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Crepitations | 5/639 (0.8%) | 5 | 4/655 (0.6%) | 4 | 7/636 (1.1%) | 8 |
| Face Oedema | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Fatigue | 10/639 (1.6%) | 12 | 21/655 (3.2%) | 22 | 7/636 (1.1%) | 7 |
| Gait Disturbance | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Generalised Oedema | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hernia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hypothermia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Influenza Like Illness | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Local Swelling | 5/639 (0.8%) | 7 | 9/655 (1.4%) | 10 | 2/636 (0.3%) | 2 |
| Malaise | 2/639 (0.3%) | 2 | 3/655 (0.5%) | 3 | 3/636 (0.5%) | 3 |
| Mass | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Medical Device Pain | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Mucosal Discolouration | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Non-Cardiac Chest Pain | 20/639 (3.1%) | 22 | 18/655 (2.7%) | 20 | 23/636 (3.6%) | 30 |
| Oedema | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Oedema Peripheral | 6/639 (0.9%) | 7 | 2/655 (0.3%) | 3 | 2/636 (0.3%) | 4 |
| Pain | 10/639 (1.6%) | 12 | 9/655 (1.4%) | 14 | 10/636 (1.6%) | 17 |
| Pyrexia | 58/639 (9.1%) | 95 | 67/655 (10.2%) | 103 | 84/636 (13.2%) | 116 |
| Tenderness | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Thirst | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Unevaluable Event | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Xerosis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Hepatic Function Abnormal | 5/639 (0.8%) | 10 | 2/655 (0.3%) | 3 | 2/636 (0.3%) | 2 |
| Hepatitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Hepatomegaly | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hyperbilirubinaemia | 2/639 (0.3%) | 3 | 5/655 (0.8%) | 7 | 2/636 (0.3%) | 3 |
| Jaundice | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Liver Tenderness | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 2 |
| Infections and infestations | ||||||
| Abscess Neck | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Acarodermatitis | 2/639 (0.3%) | 3 | 1/655 (0.2%) | 2 | 1/636 (0.2%) | 1 |
| Amoebic Dysentery | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Anal Abscess | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Body Tinea | 1/639 (0.2%) | 1 | 5/655 (0.8%) | 5 | 3/636 (0.5%) | 4 |
| Breast Abscess | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Bronchitis | 10/639 (1.6%) | 10 | 3/655 (0.5%) | 3 | 6/636 (0.9%) | 6 |
| Bronchitis Bacterial | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Bronchitis Viral | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Candida Infection | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Cellulitis | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Chest Wall Abscess | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Cystitis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Dermatitis Infected | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Dysentery | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Ear Infection | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Eye Infection | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Febrile Infection | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Folliculitis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Fungal Infection | 2/639 (0.3%) | 3 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 2 |
| Fungal Skin Infection | 5/639 (0.8%) | 7 | 3/655 (0.5%) | 3 | 3/636 (0.5%) | 5 |
| Furuncle | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Gastroenteritis | 5/639 (0.8%) | 6 | 1/655 (0.2%) | 1 | 13/636 (2%) | 14 |
| Gastroenteritis Viral | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Genital Candidiasis | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Genital Herpes | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Giardiasis | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Gingival Abscess | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Helminthic Infection | 1/639 (0.2%) | 2 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 2 |
| Herpes Zoster | 2/639 (0.3%) | 2 | 4/655 (0.6%) | 5 | 1/636 (0.2%) | 1 |
| Hiv Infection | 2/639 (0.3%) | 3 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Impetigo | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Infected Dermal Cyst | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Infected Skin Ulcer | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Infection | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Influenza | 15/639 (2.3%) | 16 | 16/655 (2.4%) | 16 | 17/636 (2.7%) | 22 |
| Laryngitis | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 3/636 (0.5%) | 3 |
| Lobar Pneumonia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 3/636 (0.5%) | 3 |
| Lower Respiratory Tract Infection | 5/639 (0.8%) | 5 | 10/655 (1.5%) | 11 | 4/636 (0.6%) | 4 |
| Lower Respiratory Tract Infection Bacterial | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Lung Abscess | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Lung Infection | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Malaria | 15/639 (2.3%) | 15 | 10/655 (1.5%) | 11 | 9/636 (1.4%) | 10 |
| Molluscum Contagiosum | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Mycobacterium Fortuitum Infection | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Myringitis | 1/639 (0.2%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nasopharyngitis | 12/639 (1.9%) | 14 | 15/655 (2.3%) | 16 | 20/636 (3.1%) | 21 |
| Oesophageal Candidiasis | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Onychomycosis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Ophthalmic Herpes Zoster | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Oral Candidiasis | 6/639 (0.9%) | 9 | 12/655 (1.8%) | 14 | 11/636 (1.7%) | 13 |
| Oral Hairy Leukoplakia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Oral Herpes | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Otitis Externa | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Otitis Media | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Otitis Media Chronic | 1/639 (0.2%) | 2 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pelvic Inflammatory Disease | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 2 | 1/636 (0.2%) | 1 |
| Pericarditis Tuberculous | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pharyngitis | 3/639 (0.5%) | 3 | 7/655 (1.1%) | 8 | 7/636 (1.1%) | 7 |
| Pharyngotonsillitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pneumocystis Jirovecii Pneumonia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Pneumonia | 6/639 (0.9%) | 9 | 3/655 (0.5%) | 5 | 7/636 (1.1%) | 7 |
| Pneumonia Bacterial | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Pneumonia Haemophilus | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pulmonary Tuberculosis | 14/639 (2.2%) | 14 | 24/655 (3.7%) | 27 | 36/636 (5.7%) | 37 |
| Pulpitis Dental | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pyelonephritis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Rash Pustular | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 4 |
| Respiratory Tract Infection | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 3 | 3/636 (0.5%) | 3 |
| Respiratory Tract Infection Viral | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Rhinitis | 10/639 (1.6%) | 11 | 13/655 (2%) | 16 | 18/636 (2.8%) | 21 |
| Schistosomiasis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Schistosomiasis Bladder | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Septic Rash | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 8 |
| Sinusitis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 3 |
| Subcutaneous Abscess | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Tinea Capitis | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 5 | 0/636 (0%) | 0 |
| Tinea Faciei | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tinea Infection | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Tinea Pedis | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 3/636 (0.5%) | 4 |
| Tinea Versicolour | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 4/636 (0.6%) | 5 |
| Tonsillitis | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Tooth Abscess | 1/639 (0.2%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 2 |
| Tooth Infection | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Tuberculosis | 3/639 (0.5%) | 3 | 11/655 (1.7%) | 11 | 8/636 (1.3%) | 9 |
| Tuberculosis Gastrointestinal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Typhoid Fever | 3/639 (0.5%) | 3 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Upper Respiratory Tract Infection | 24/639 (3.8%) | 27 | 20/655 (3.1%) | 23 | 20/636 (3.1%) | 24 |
| Upper Respiratory Tract Infection Bacterial | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Urinary Tract Infection | 8/639 (1.3%) | 9 | 7/655 (1.1%) | 8 | 11/636 (1.7%) | 12 |
| Vaginitis Bacterial | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Varicella | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Viral Infection | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Viral Upper Respiratory Tract Infection | 7/639 (1.1%) | 13 | 6/655 (0.9%) | 11 | 7/636 (1.1%) | 11 |
| Vulvovaginal Candidiasis | 5/639 (0.8%) | 8 | 7/655 (1.1%) | 9 | 6/636 (0.9%) | 8 |
| Vulvovaginitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Wound Infection | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Wound Sepsis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Accident | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Animal Bite | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Ankle Fracture | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Contusion | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 4/636 (0.6%) | 4 |
| Excoriation | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 2 |
| Eyelid Injury | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Fall | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Fibula Fracture | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Foreign Body | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Foreign Body In Eye | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hand Fracture | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Human Bite | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Humerus Fracture | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Incorrect Dose Administered | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Injury Corneal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Jaw Fracture | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Joint Injury | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Laceration | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 4/636 (0.6%) | 5 |
| Ligament Sprain | 0/639 (0%) | 0 | 2/655 (0.3%) | 4 | 2/636 (0.3%) | 2 |
| Lip Injury | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Muscle Strain | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 1/636 (0.2%) | 1 |
| Periorbital Contusion | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Rib Fracture | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Road Traffic Accident | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Scar | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Skeletal Injury | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Soft Tissue Injury | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 3/636 (0.5%) | 3 |
| Stab Wound | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Subdural Haematoma | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Thermal Burn | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Tibia Fracture | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Tooth Fracture | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Wound | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Investigations | ||||||
| Activated Partial Thromboplastin Time Prolonged | 10/639 (1.6%) | 13 | 10/655 (1.5%) | 13 | 13/636 (2%) | 16 |
| Alanine Aminotransferase Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Alanine Aminotransferase Decreased | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Alanine Aminotransferase Increased | 25/639 (3.9%) | 37 | 30/655 (4.6%) | 39 | 16/636 (2.5%) | 24 |
| Amylase Increased | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Aspartate Aminotransferase Increased | 28/639 (4.4%) | 41 | 35/655 (5.3%) | 47 | 24/636 (3.8%) | 31 |
| Blood Albumin Decreased | 1/639 (0.2%) | 3 | 2/655 (0.3%) | 3 | 2/636 (0.3%) | 2 |
| Blood Bilirubin Increased | 4/639 (0.6%) | 4 | 9/655 (1.4%) | 14 | 2/636 (0.3%) | 6 |
| Blood Creatine Increased | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Blood Creatinine Decreased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Blood Creatinine Increased | 7/639 (1.1%) | 8 | 15/655 (2.3%) | 17 | 7/636 (1.1%) | 10 |
| Blood Glucose Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Blood Glucose Increased | 2/639 (0.3%) | 4 | 3/655 (0.5%) | 9 | 0/636 (0%) | 0 |
| Blood Potassium Decreased | 0/639 (0%) | 0 | 3/655 (0.5%) | 3 | 4/636 (0.6%) | 5 |
| Blood Potassium Increased | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Blood Pressure Decreased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Blood Pressure Diastolic Decreased | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Blood Pressure Diastolic Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Blood Pressure Increased | 6/639 (0.9%) | 7 | 6/655 (0.9%) | 7 | 7/636 (1.1%) | 8 |
| Blood Pressure Systolic Decreased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Blood Pressure Systolic Increased | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 4 | 0/636 (0%) | 0 |
| Blood Sodium Decreased | 4/639 (0.6%) | 9 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Blood Sodium Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 4/636 (0.6%) | 5 |
| Blood Urea Increased | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Blood Uric Acid Increased | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Body Temperature Increased | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Breath Sounds Abnormal | 7/639 (1.1%) | 9 | 9/655 (1.4%) | 10 | 5/636 (0.8%) | 6 |
| Cardiac Murmur | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Cd4 Lymphocytes Decreased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Chest X-Ray Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Coagulation Test Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Colour Vision Tests Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Creatinine Renal Clearance Decreased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Gamma-Glutamyltransferase Increased | 2/639 (0.3%) | 4 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Gastrointestinal Examination Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Glucose Urine Present | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Haemoglobin Decreased | 13/639 (2%) | 24 | 18/655 (2.7%) | 29 | 20/636 (3.1%) | 28 |
| Heart Rate Increased | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Heart Rate Irregular | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 3 |
| Heart Sounds Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hepatic Enzyme Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hepatic Enzyme Increased | 22/639 (3.4%) | 36 | 18/655 (2.7%) | 30 | 11/636 (1.7%) | 17 |
| International Normalised Ratio Abnormal | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| International Normalised Ratio Increased | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Liver Function Test Abnormal | 2/639 (0.3%) | 4 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Liver Palpable Subcostal | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Lymph Node Palpable | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Neutrophil Count Decreased | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 0/636 (0%) | 0 |
| Neutrophil Percentage Decreased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Ophthalmological Examination Abnormal | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Percussion Test Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Platelet Count Decreased | 5/639 (0.8%) | 5 | 3/655 (0.5%) | 6 | 4/636 (0.6%) | 4 |
| Prothrombin Level Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Prothrombin Time Abnormal | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Prothrombin Time Prolonged | 11/639 (1.7%) | 15 | 13/655 (2%) | 16 | 20/636 (3.1%) | 30 |
| Pulmonary Physical Examination Abnormal | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Red Blood Cell Sedimentation Rate Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Respiratory Rate Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Transaminases Increased | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Urine Analysis Abnormal | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Urine Cytology Abnormal | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Urine Leukocyte Esterase Positive | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Weight Decreased | 62/639 (9.7%) | 83 | 70/655 (10.7%) | 85 | 72/636 (11.3%) | 77 |
| White Blood Cell Count Decreased | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| White Blood Cell Count Increased | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Abnormal Loss Of Weight | 15/639 (2.3%) | 22 | 20/655 (3.1%) | 23 | 16/636 (2.5%) | 18 |
| Cachexia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Decreased Appetite | 45/639 (7%) | 54 | 33/655 (5%) | 35 | 45/636 (7.1%) | 50 |
| Dehydration | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Diabetes Mellitus | 6/639 (0.9%) | 10 | 7/655 (1.1%) | 9 | 9/636 (1.4%) | 13 |
| Diabetes Mellitus Inadequate Control | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 1/636 (0.2%) | 1 |
| Electrolyte Imbalance | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hypercholesterolaemia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hyperglycaemia | 3/639 (0.5%) | 3 | 3/655 (0.5%) | 6 | 2/636 (0.3%) | 5 |
| Hyperkalaemia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 3/636 (0.5%) | 3 |
| Hypernatraemia | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Hyperuricaemia | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 3 | 1/636 (0.2%) | 1 |
| Hypoglycaemia | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hypokalaemia | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 4 | 1/636 (0.2%) | 1 |
| Hyponatraemia | 4/639 (0.6%) | 5 | 5/655 (0.8%) | 6 | 1/636 (0.2%) | 1 |
| Iron Deficiency | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Metabolic Acidosis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Polydipsia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Vitamin B Complex Deficiency | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 10/639 (1.6%) | 182 | 12/655 (1.8%) | 177 | 10/636 (1.6%) | 162 |
| Arthritis | 6/639 (0.9%) | 7 | 6/655 (0.9%) | 12 | 1/636 (0.2%) | 1 |
| Arthropathy | 3/639 (0.5%) | 3 | 4/655 (0.6%) | 7 | 2/636 (0.3%) | 2 |
| Arthrotoxicity | 1/639 (0.2%) | 2 | 3/655 (0.5%) | 5 | 4/636 (0.6%) | 7 |
| Back Pain | 19/639 (3%) | 26 | 20/655 (3.1%) | 24 | 20/636 (3.1%) | 22 |
| Bursitis | 1/639 (0.2%) | 2 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Chondrotoxicity | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 3 | 1/636 (0.2%) | 1 |
| Clubbing | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Costochondritis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Fibromyalgia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Finger Deformity | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Flank Pain | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 4/636 (0.6%) | 4 |
| Gouty Arthritis | 2/639 (0.3%) | 4 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Joint Range Of Motion Decreased | 1/639 (0.2%) | 2 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Joint Stiffness | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 3 | 1/636 (0.2%) | 1 |
| Joint Swelling | 5/639 (0.8%) | 6 | 4/655 (0.6%) | 5 | 6/636 (0.9%) | 9 |
| Ligament Pain | 2/639 (0.3%) | 3 | 2/655 (0.3%) | 3 | 0/636 (0%) | 0 |
| Metatarsalgia | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Muscle Atrophy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Muscle Fatigue | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Muscle Spasms | 10/639 (1.6%) | 11 | 6/655 (0.9%) | 10 | 4/636 (0.6%) | 4 |
| Muscle Swelling | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Muscular Weakness | 3/639 (0.5%) | 4 | 5/655 (0.8%) | 5 | 2/636 (0.3%) | 2 |
| Musculoskeletal Chest Pain | 1/639 (0.2%) | 1 | 3/655 (0.5%) | 5 | 0/636 (0%) | 0 |
| Musculoskeletal Discomfort | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Musculoskeletal Disorder | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Musculoskeletal Pain | 12/639 (1.9%) | 17 | 11/655 (1.7%) | 12 | 7/636 (1.1%) | 8 |
| Musculoskeletal Stiffness | 4/639 (0.6%) | 5 | 4/655 (0.6%) | 6 | 1/636 (0.2%) | 1 |
| Myalgia | 14/639 (2.2%) | 15 | 28/655 (4.3%) | 41 | 21/636 (3.3%) | 25 |
| Myopathy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Myositis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Neck Pain | 3/639 (0.5%) | 4 | 6/655 (0.9%) | 6 | 2/636 (0.3%) | 3 |
| Osteoarthritis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pain In Extremity | 32/639 (5%) | 44 | 27/655 (4.1%) | 38 | 29/636 (4.6%) | 43 |
| Periarthritis | 3/639 (0.5%) | 4 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Polyarthritis | 0/639 (0%) | 0 | 1/655 (0.2%) | 3 | 0/636 (0%) | 0 |
| Sensation Of Heaviness | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Spinal Pain | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Synovial Cyst | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tendon Disorder | 2/639 (0.3%) | 3 | 5/655 (0.8%) | 6 | 4/636 (0.6%) | 4 |
| Tendon Pain | 3/639 (0.5%) | 3 | 4/655 (0.6%) | 4 | 3/636 (0.5%) | 3 |
| Tendonitis | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 3 | 1/636 (0.2%) | 1 |
| Trigger Finger | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Upper Extremity Mass | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Anogenital Warts | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Penile Wart | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pharyngeal Neoplasm Benign | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Thyroid Neoplasm | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nervous system disorders | ||||||
| Ageusia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Burning Sensation | 2/639 (0.3%) | 3 | 3/655 (0.5%) | 3 | 0/636 (0%) | 0 |
| Coma | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Convulsion | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Dizziness | 15/639 (2.3%) | 17 | 16/655 (2.4%) | 25 | 26/636 (4.1%) | 32 |
| Dizziness Postural | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Dysgeusia | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Epilepsy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Headache | 35/639 (5.5%) | 44 | 39/655 (6%) | 45 | 52/636 (8.2%) | 63 |
| Hemiparesis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hemiplegia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hyperaesthesia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hyperreflexia | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hypoaesthesia | 8/639 (1.3%) | 14 | 8/655 (1.2%) | 9 | 12/636 (1.9%) | 19 |
| Lethargy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 3/636 (0.5%) | 3 |
| Loss Of Consciousness | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Memory Impairment | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Migraine | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Neuralgia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Neuritis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Neuropathy Peripheral | 13/639 (2%) | 16 | 6/655 (0.9%) | 6 | 11/636 (1.7%) | 14 |
| Paraesthesia | 8/639 (1.3%) | 12 | 10/655 (1.5%) | 13 | 3/636 (0.5%) | 5 |
| Parosmia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Post Herpetic Neuralgia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Restless Legs Syndrome | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Sciatica | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Sensory Disturbance | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Somnolence | 6/639 (0.9%) | 6 | 5/655 (0.8%) | 8 | 7/636 (1.1%) | 7 |
| Syncope | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Tension Headache | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Tremor | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Visual Field Defect | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion Threatened | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Pregnancy | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 4 | 0/636 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 5/636 (0.8%) | 5 |
| Anxiety Disorder | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Confusional State | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 3 |
| Depression | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Hallucination | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Initial Insomnia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Insomnia | 12/639 (1.9%) | 16 | 6/655 (0.9%) | 6 | 6/636 (0.9%) | 6 |
| Nervousness | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Premature Ejaculation | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Psychotic Disorder | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Sleep Disorder | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Tension | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Renal and urinary disorders | ||||||
| Bilirubinuria | 0/639 (0%) | 0 | 5/655 (0.8%) | 5 | 0/636 (0%) | 0 |
| Dysuria | 6/639 (0.9%) | 7 | 5/655 (0.8%) | 5 | 2/636 (0.3%) | 2 |
| Enuresis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Glycosuria | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 3/636 (0.5%) | 5 |
| Haematuria | 2/639 (0.3%) | 2 | 3/655 (0.5%) | 3 | 4/636 (0.6%) | 6 |
| Leukocyturia | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 4 | 1/636 (0.2%) | 1 |
| Nephrolithiasis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nocturia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pollakiuria | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Polyuria | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Proteinuria | 3/639 (0.5%) | 3 | 6/655 (0.9%) | 6 | 7/636 (1.1%) | 8 |
| Renal Colic | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Renal Failure Acute | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Urethral Discharge | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Urinary Incontinence | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Urinary Retention | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Breast Discharge | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Breast Pain | 2/639 (0.3%) | 4 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Dysmenorrhoea | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Erectile Dysfunction | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Fibrocystic Breast Disease | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Genital Rash | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 2 |
| Genital Ulceration | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Menometrorrhagia | 1/639 (0.2%) | 4 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Menorrhagia | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Menstruation Irregular | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Nipple Pain | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Penile Discharge | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Polymenorrhoea | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pruritus Genital | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Testicular Pain | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Vaginal Discharge | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Vaginal Disorder | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Vaginal Haemorrhage | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Vulvovaginal Pruritus | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 4 | 1/636 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Allergic Bronchitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Asphyxia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Aspiration | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Asthma | 1/639 (0.2%) | 2 | 5/655 (0.8%) | 7 | 4/636 (0.6%) | 4 |
| Atelectasis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Bronchiectasis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Bronchospasm | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Chronic Obstructive Pulmonary Disease | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Cough | 85/639 (13.3%) | 107 | 11/655 (1.7%) | 136 | 13/636 (2%) | 188 |
| Dysphonia | 2/639 (0.3%) | 2 | 3/655 (0.5%) | 3 | 1/636 (0.2%) | 1 |
| Dyspnoea | 49/639 (7.7%) | 70 | 54/655 (8.2%) | 67 | 79/636 (12.4%) | 99 |
| Dyspnoea Exertional | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Epistaxis | 4/639 (0.6%) | 4 | 2/655 (0.3%) | 2 | 2/636 (0.3%) | 3 |
| Haemoptysis | 51/639 (8%) | 59 | 55/655 (8.4%) | 71 | 40/636 (6.3%) | 47 |
| Hiccups | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hyperventilation | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Hypoventilation | 5/639 (0.8%) | 8 | 8/655 (1.2%) | 9 | 5/636 (0.8%) | 6 |
| Mediastinal Shift | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nasal Congestion | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Nasal Discomfort | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Nasal Obstruction | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Nasal Oedema | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Nasal Ulcer | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Obstructive Airways Disorder | 0/639 (0%) | 0 | 1/655 (0.2%) | 2 | 0/636 (0%) | 0 |
| Oropharyngeal Pain | 7/639 (1.1%) | 8 | 10/655 (1.5%) | 10 | 11/636 (1.7%) | 11 |
| Pharyngeal Erythema | 3/639 (0.5%) | 3 | 3/655 (0.5%) | 3 | 4/636 (0.6%) | 4 |
| Pharyngeal Oedema | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 3 |
| Pleural Effusion | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Pleural Rub | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Pleuritic Pain | 5/639 (0.8%) | 7 | 5/655 (0.8%) | 6 | 18/636 (2.8%) | 19 |
| Pneumonitis | 1/639 (0.2%) | 2 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Pneumothorax | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Productive Cough | 3/639 (0.5%) | 3 | 3/655 (0.5%) | 4 | 10/636 (1.6%) | 10 |
| Pulmonary Arterial Hypertension | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pulmonary Congestion | 1/639 (0.2%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Pulmonary Hilum Mass | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Pulmonary Hypertension | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Rales | 11/639 (1.7%) | 17 | 10/655 (1.5%) | 11 | 18/636 (2.8%) | 20 |
| Respiratory Disorder | 46/639 (7.2%) | 58 | 52/655 (7.9%) | 63 | 54/636 (8.5%) | 69 |
| Respiratory Fremitus | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Rhinitis Allergic | 2/639 (0.3%) | 3 | 2/655 (0.3%) | 4 | 5/636 (0.8%) | 5 |
| Rhinorrhoea | 11/639 (1.7%) | 12 | 7/655 (1.1%) | 8 | 4/636 (0.6%) | 5 |
| Rhonchi | 0/639 (0%) | 0 | 3/655 (0.5%) | 3 | 1/636 (0.2%) | 1 |
| Sneezing | 1/639 (0.2%) | 1 | 4/655 (0.6%) | 5 | 2/636 (0.3%) | 2 |
| Tachypnoea | 3/639 (0.5%) | 3 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Throat Irritation | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Tonsillar Hypertrophy | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Tonsillar Inflammation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Upper-Airway Cough Syndrome | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Wheezing | 6/639 (0.9%) | 10 | 7/655 (1.1%) | 8 | 9/636 (1.4%) | 11 |
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 4/636 (0.6%) | 4 |
| Alopecia | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Angioedema | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Blister | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Chloasma | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Dermal Cyst | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Dermatitis | 6/639 (0.9%) | 7 | 4/655 (0.6%) | 5 | 3/636 (0.5%) | 3 |
| Dermatitis Acneiform | 2/639 (0.3%) | 3 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Dermatitis Allergic | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Dermatitis Bullous | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Dermatitis Contact | 3/639 (0.5%) | 4 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Diabetic Foot | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Dry Skin | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Eczema | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 1/636 (0.2%) | 1 |
| Erythema | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 3 |
| Exfoliative Rash | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hand Dermatitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Hyperhidrosis | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hyperkeratosis | 0/639 (0%) | 0 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Intertrigo | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Milia | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Miliaria | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Night Sweats | 29/639 (4.5%) | 32 | 48/655 (7.3%) | 50 | 57/636 (9%) | 61 |
| Pemphigus | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Pruritus | 39/639 (6.1%) | 46 | 35/655 (5.3%) | 52 | 37/636 (5.8%) | 47 |
| Pruritus Generalised | 18/639 (2.8%) | 22 | 16/655 (2.4%) | 20 | 9/636 (1.4%) | 12 |
| Rash | 25/639 (3.9%) | 33 | 18/655 (2.7%) | 20 | 22/636 (3.5%) | 32 |
| Rash Generalised | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Rash Macular | 4/639 (0.6%) | 5 | 5/655 (0.8%) | 7 | 2/636 (0.3%) | 2 |
| Rash Maculo-Papular | 5/639 (0.8%) | 6 | 4/655 (0.6%) | 4 | 4/636 (0.6%) | 4 |
| Rash Maculovesicular | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Rash Papular | 6/639 (0.9%) | 6 | 7/655 (1.1%) | 8 | 8/636 (1.3%) | 13 |
| Rash Pruritic | 9/639 (1.4%) | 12 | 4/655 (0.6%) | 4 | 5/636 (0.8%) | 8 |
| Seborrhoeic Dermatitis | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 2 |
| Skin Discolouration | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Skin Exfoliation | 3/639 (0.5%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Skin Hyperpigmentation | 1/639 (0.2%) | 1 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Skin Hypopigmentation | 2/639 (0.3%) | 4 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Skin Lesion | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 3 |
| Skin Reaction | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Skin Ulcer | 0/639 (0%) | 0 | 2/655 (0.3%) | 3 | 1/636 (0.2%) | 1 |
| Skin Warm | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Swelling Face | 1/639 (0.2%) | 1 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Urticaria | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 0/636 (0%) | 0 |
| Social circumstances | ||||||
| Cosmetic Body Piercing | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Physical Assault | 3/639 (0.5%) | 3 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Victim Of Crime | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 2/636 (0.3%) | 2 |
| Surgical and medical procedures | ||||||
| Cataract Operation | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Ear Operation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Eye Prosthesis Insertion | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Finger Amputation | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Leg Amputation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Tooth Extraction | 2/639 (0.3%) | 2 | 2/655 (0.3%) | 2 | 1/636 (0.2%) | 1 |
| Vascular disorders | ||||||
| Deep Vein Thrombosis | 1/639 (0.2%) | 3 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Diastolic Hypertension | 1/639 (0.2%) | 2 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Haematoma | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hot Flush | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Hypertension | 15/639 (2.3%) | 28 | 18/655 (2.7%) | 30 | 10/636 (1.6%) | 16 |
| Hypertensive Crisis | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Hypotension | 2/639 (0.3%) | 2 | 1/655 (0.2%) | 1 | 5/636 (0.8%) | 5 |
| Orthostatic Hypotension | 2/639 (0.3%) | 2 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Pallor | 2/639 (0.3%) | 2 | 4/655 (0.6%) | 4 | 1/636 (0.2%) | 1 |
| Phlebitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 1/636 (0.2%) | 1 |
| Poor Peripheral Circulation | 0/639 (0%) | 0 | 1/655 (0.2%) | 1 | 0/636 (0%) | 0 |
| Systolic Hypertension | 0/639 (0%) | 0 | 0/655 (0%) | 0 | 2/636 (0.3%) | 2 |
| Thrombophlebitis | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
| Varicose Vein | 1/639 (0.2%) | 1 | 0/655 (0%) | 0 | 0/636 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Daniel E. Everitt, MD, Vice President and Senior Medical Officer |
|---|---|
| Organization | Global Alliance for TB Drug Development |
| Phone | (212) 227-7540 |
| Dan.Everitt@tballiance.org |
Responsible Party:
Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier:
NCT00864383
Other Study ID Numbers:
- REMoxTB
- ISRCTN85595810
First Posted:
Mar 18, 2009
Last Update Posted:
Mar 21, 2017
Last Verified:
Feb 1, 2017