CTRI/2025/12/099360 [Registered on: 17/12/2025] Trial Registered Prospectively
Last Modified On:
07/04/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Phase III study to determine Efficacy, Safety and Tolerability of Oral Nafithromycin in comparison with Oral Amoxicillin-Clavulanic Acid and Azithromycin in adult participants with Acute Bacterial RhinoSinusitis (ABRS)
Scientific Title of Study
A Phase III, Randomized, Open-label, Multicenter, Comparative Study to Evaluate the Efficacy, Safety and Tolerability of Oral Nafithromycin (WCK 4873) Versus Combination of Oral Amoxicillin-Clavulanic Acid And Azithromycin in the Treatment of Acute Bacterial Rhinosinusitis (ABRS) in Adults
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
W-4873-302 Amendment 2 Version 3.0 Dated 28 Oct 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Sachin Bhagwat
Designation
Chief Scientific Officer, Drug Discovery
Affiliation
Wockhardt Research Centre
Address
Division - Drug Discovery Research Department- Microbiology D-4 MIDC, Chikalthana
Aurangabad MAHARASHTRA 431006 India
Phone
02406694185
Fax
Email
sbhagwat@wockhardt.com
Details of Contact Person Public Query
Name
Dr Sachin Bhagwat
Designation
Chief Scientific Officer, Drug Discovery
Affiliation
Wockhardt Research Centre
Address
Division - Drug Discovery Research Department- Microbiology D-4 MIDC, Chikalthana
MAHARASHTRA 431006 India
Phone
02406694185
Fax
Email
sbhagwat@wockhardt.com
Source of Monetary or Material Support
Wockhardt Ltd, D-4, MIDC, Chikalthana, Chhatrapati Sambhajinagar – 431006, India.
Primary Sponsor
Name
Ms Wockhardt Limited
Address
Wockhardt Ltd, D-4, MIDC, Chikalthana, Chhatrapati Sambhajinagar – 431006, India.
Room No- 213, ENT Department, Mihan, Nagpur, Maharashtra- 441108, India. Nagpur MAHARASHTRA
8237791561
sandy.emt@gmail.com
Dr Sandeep Katiyar
Apollo Spectra Hospital
B-20, Basement, Apollo Spectra Hospital, 14/138, Chunni Ganj, Kanpur-208001, Uttar Pradesh, India. Kanpur Nagar UTTAR PRADESH
9889888080
skkatiyarin@gmail.com
Dr Manjunatha Rao S V
Basaveshwara Medical Collage and Hospital
OPD-03, ENT Department, NH4 Chitradurga, Karnataka-577502, India. Chitradurga KARNATAKA
8792995867
investigator.research12@gmail.com
Dr Karthika Bhagavan
Belagavi Institute of Medical Sciences
OPD- 50, Third floor, ENT Department, Belagavi Institute of Medical Sciences, Dr. B R Ambedkar Road, Sada Shiv Nagar , Belgavi, Karnataka-590019, India. Belgaum KARNATAKA
8312491071
belgaum.bims@gmail.com
Dr C V Srinivas
Dr. B R Ambedkar Medical College and Hospital
OPD- 24, ENT Department, No. 24, Shampura, Kadugondanahalli , Bengaluru, Karnataka- 560045, India. Bangalore KARNATAKA
8151994080
ambedkarhospital.crc@gmail.com
Dr Diyya Sudheer
Government Hospital for Chest and Communicable Diseases (GHCCD)
OPD-01, Ground Floor, Government Hospital for Chest and Communicable Diseases (GHCCD) , Gorantala , Guntur, Andhra Pradesh- 522034, India. Guntur ANDHRA PRADESH
8919069428
dsudheer.dr@gmail.com
Dr Sudeena Dullapalli
Govt. Siddhartha Medical College
Room No- 218, Second Floor,Department of Pulmonary medicines, Ring Road Gunadala, Vijayawada, Andhra Pradesh-520008, India. Krishna ANDHRA PRADESH
9866059523
drsudeenara@gmail.com
Dr B Tata Rao
Great Eastern Medical School & Hospital
OPD-01, Ground Floor, ENT Department, Gems Medical College Road, Aditya Educational Society Srikakulam, Ragolu, Andhra Pradesh 532484, India. Srikakulam ANDHRA PRADESH
7893777399
drbtataraoresearch@gmail.com
Dr Amrita Srivastava
GSVM Medical College
Room No 04, ENT Department, Swaroop Nagar, Kanpur, Uttar Pradesh-208002, India. Kanpur Nagar UTTAR PRADESH
8650439887
dramrita.srivastava@gmail.com
Dr Mundhe Ram Govindrao
Gunjkar Multispeciality Hospital
OPD-03, ENT Department, Plot No. 315, Sector No. 18, Spine
Rd, Shivtej Nagar, Chinchwad,
Vitthal Nagar, Pune, Maharashtra 411019, India. Pune MAHARASHTRA
8454859082
drmundhe.gunjkarhospital@email.com
Dr Digvijay Singh Rawat
Jawahar Lal Nehru Medical College
Room No-17, Ground Floor, Jawaharlal Nehru Medical College, Kala Bagh, Ajmer - 305001, Rajasthan, India Ajmer RAJASTHAN
9460331895
drdigvijaysingh231@gmail.com
Dr Ranjith Vijay Kumar
K R Hospital
OPD-No-01, Ground Floor, OPD Building, Department of Medicine, Mysore Medical Collage and Research Institute, Irwin road, Mysore, Karnataka-570001, India. Mysore KARNATAKA
9448188588
ranjithvmmcri@gmail.com
Dr Shivprakash Mehta
Kothrud Hospital
OPD- 01, ENT Department, Gadiya Estate, Paud Rd, opposite Hill View Park, Bhagya Chintamani Nagar, Guruganesh Nagar, Kothrud, Pune, Maharashtra-411038, India. Pune MAHARASHTRA
8048059328
hkreception22@gmail.com
Dr Vishal Modi
Mavajat Hospital
OPD- 13, ENT Department, Mavjat Multispeciality Hospital, Mansarovar Lake Rd,
Bank Colony, Palanpur, Gujarat-385001, India. Banas Kantha GUJARAT
9574564949
modivishal13@gmail.com
Dr Rahul Aggarwal
Max Superspeciality Hospital
OPD-148, ENT Department, Max Super Speciality Hospital, Vaishali, W-3, Sector-1, Vaishali, Ghaziabad- 201012, Uttar pradesh, India. Ghaziabad UTTAR PRADESH
9810588621
rahul.aggrawal.ent@gmail.com
Dr Saumik Das
North Bengal Medical College and Hospital
OPD-10-11, Ground Floor, ENT Department, Sushruta Nagar, Siliguri, West Bengal-734012, India. Darjiling WEST BENGAL
OPD 04, Basement Floor, Calgiri Marg, near Police Station, Jhalana Gram, Malviya Nagar, Jaipur, Rajasthan-302017, India. Jaipur RAJASTHAN
9818055846
dms@rungtahospital.com
Dr Akhil Pratap Singh
S N Medical College & Hospital
Room No- 04, ENT Department, Raja Mandi, Near Central Library, Moti Katra, Mantola, Agra, Uttar Pradesh - 282003, India. Agra UTTAR PRADESH
7095464858
dr.akhilpratap1@gmail.com
Dr Monica Gupta
Samvedna Hospital
OPD-01, Department of General Medicine, Samvedna Hospital, B-27/88G, Durgakund road, opposite IP Vijaya Mall, Bhelupur, Varanasi, Uttar Pradesh-221005, India. Varanasi UTTAR PRADESH
9415336322
monicag@yahoo.com
Dr Mukesh More
Supe Heart and Diabetes Hospital and Research Centre
Room No- 03, ENT Department, Gharapure Ghat Rd, Near Rungta High School, Ashok Stambh, Raviwa Panchavati, Nashik, Maharashtra-422002, India. Nashik MAHARASHTRA
9224507915
drmukeshmore29@gmail.com
Dr Mohit Ruparel
V-Cure Hospital
OPD-02, 5th Floor, ENT Department , Gate 2, 5th Floor Ashwamegh Elegance III, Ambawadi Cir, opposite CN Vidyalaya, beside Grand Mall, Ambawadi, Ahmedabad, Gujarat 380015, India. Ahmadabad GUJARAT
9925474750
mohit23386@gmail.com
Dr Viral Prajapati
Viral Multisuper Speciality Hospital
Room no-03, 1st floor, ENT Department, Prabhat Chowk, Viral Multi-Super Speciality Hospital, opposite ADC bank, near Nutan English Medium School, Ghatlodia, Ahmedabad, Gujarat-380061, India. Ahmadabad GUJARAT
Strength and pharmaceutical dosage form: 625 mg tablets
Dose: 625 mg thrice daily for 5-7 days
Route of Administration: Oral
Comparator Agent
Azithromycin
Strength and pharmaceutical dosage form: 500 mg tablets
Dose: 500 mg once daily for 3 days
Route of Administration: Oral
Intervention
Nafithromycin
Strength and pharmaceutical dosage form: 400 mg tablet
Dose: 400 mg once daily on Day 1 through Day 3
Route of Administration: Oral
Inclusion Criteria
Age From
18.00 Year(s)
Age To
90.00 Year(s)
Gender
Both
Details
1. Male or female greater than equal to 18 years of age
2. Willing to participate in the study and provide written informed consent before any protocol-specific assessment is performed.
3. Clinical diagnosis of ABRS in accordance with the guidelines of the Infectious Disease Society of America (IDSA), i.e., fitting into one of 3 categories. The 3 IDSA categories are
• Persistent symptoms of rhinitis, purulent secretions, and/or pain in the face or teeth without improvement (lasting for greater than equal 10 days), OR
• Severe symptoms or signs of fever of at least 102 °F and nasal discharge or facial pain (lasting for greater than equal 3 to 4 days), OR
• Worsening symptoms or signs characterized by a new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory illness that lasted 5 to 6 days and was initially improving (double sickening).
4. Trial participants have at least 2 out of 5 symptoms of ABRS mentioned in the ABRS symptom questionnaire such as purulent nasal discharge, blocked nose, facial pain, chills/rigor and pressure around eyes, nose and cheek, forehead.
5. Trial participants have a baseline CT sinus imaging, done not more than 48 hrs prior to randomization and having findings consistent with ABRS.
6. All females must have had a negative urine or serum pregnancy test (beta human chorionic gonadotropin [beta HCG]) at Screening AND agreed to the use of 1 of the following acceptable methods of contraception from Screening through Day 8: surgical sterilization (defined as bilateral oophorectomy or bilateral salpingectomy, but excluding bilateral tubal occlusion), post-menopausal women (defined by amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments), barrier contraception (Example. condom, intrauterine device), levonorgestrel intrauterine system example Mirena, regular medroxyprogesterone injections Example Depo-provera, sexual intercourse with only vasectomized partners or abstinence.
7. All males must have agreed to use an acceptable barrier method of birth control (i.e. condom) with female partner(s) and must not donate sperm from Screening through Day 8.
8. Ability to ingest the intact oral study drug.
ExclusionCriteria
Details
1. Trial participants who have severe infection requiring surgical drainage of sinuses or parenteral antibiotic therapy or needing hospitalization.
2. Presence or known diagnosis of Allergic rhinitis
3. Presence or known diagnosis of Nasal polyposis requiring surgery
4. Suspected or confirmed complications such as preseptal cellulitis, orbital cellulitis, subperiosteal abscess, orbital abscess, cavernous sinus
thrombophlebitis, acute mastoiditis, facial palsy and bacterial meningitis in the opinion of Investigator.
5. Trial participants who have received more than a single dose of systemic antibacterial treatment for ABRS within the last 72 hrs, with exception of participants who are not responding to the current antibiotic treatment according to the Investigator.
6. Need of concomitant use of other antibiotics.
7. Chronic or recurrent “sinus” problems. Defined as persistent symptoms of “sinus” congestion, not attributed to nasal allergies, for 8 weeks or more or 2 or more episodes of antibiotic-treated “sinusitis” in past 3 months.
8. Known or suspected sinus fungal or viral cause of infection
9. Presence or history of recent trauma or recent surgery with last 4 weeks.
10. Known to have had Methicillin-resistant Staphylococcus aureus (MRSA) sinus infection within the past month.
11. History of hospitalization in the last 90 days before screening
12. Use of any experimental drug or device within 30 days prior to enrolment
13. History of allergy or intolerance to any penicillin or amoxicillin clavulanate or macrolides and their excipients.
14. History or of hypersensitivity, known contraindication (example. lactose intolerance, lactase deficiency or glucose-galactose malabsorption) or allergic reaction (example. anaphylaxis, urticaria, other significant reaction) to any macrolide or beta-lactam antibiotic or beta-lactamase inhibitor (any of the study drug or its ingredients).
15. Evidence of significant immunologic disease determined by any of the following:
• Current or anticipated neutropenia defined as less than 500 neutrophils,mm3
• History of heart, lung, liver or kidney transplant
• Receipt of cancer chemotherapy, radiotherapy or potent, non-corticosteroid immunosuppressant drugs (e.g., cyclosporine, azathioprine, tacrolimus, immune-modulating monoclonal antibody therapy) within the past 3 months or receipt of corticosteroids equivalent to or greater than 40 mg of prednisone per day for more than 14 days in the 30 days before randomization.
16. Compromised hepatic or renal function, including but not limited to the following: clinical evidence of end stage liver disease (Example. ascites, hepatic encephalopathy), screening serum total bilirubin greater then 2 times the Upper Limit of Normal ULN (unless associated with an elevated indirect bilirubin typical of Gilbert syndrome), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater then or equal to 3 times the ULN, serum creatinine greater than 2.0 mg/dL creatinine clearance less than 50 mL/min or blood urea nitrogen greater then 30 mg/dL; other clinically significant abnormal laboratory findings should be discussed with the Medical Monitor before the enrollment of the trial participants.
17. History of Clostridium difficile-associated disease within 6 months before enrolment.
18. Trial Participants with prior treatment with or concomitant use of CYP liver enzyme inducers (example. phenobarbital, carbamazepine, griseofulvin, sulfonylureas, phenytoin or rifampin), cancer chemotherapy, radiotherapy or potent, non-corticosteroid immunosuppressant drugs (example. cyclosporine, azathioprine, tacrolimus or immune-modulating monoclonal antibody therapy) within the past 3 months or have received corticosteroids equivalent to or greater than 40 mg of prednisone per day for more than 14 days in the 30 days before randomization and trial participants who received any experimental drug within 30 days before enrolment.
19. Current second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months before the Screening visit, clinically significant ECG abnormalities including QT interval corrected for heart rate using Fridericia’s formula (QTcF) greater than 450 ms (males) or greater than 470 ms (females) or requirement for medications known to cause QT prolongation.
20. Nursing mothers or pregnant females
21. Require admission to an intensive care unit for any reason, life expectancy of less than 2 months or any concomitant condition that in the opinion of the Investigator is likely to interfere with evaluation of the response of the infection under study, determination of AEs or completion of the expected course of treatment.
22. Current peripheral neuropathy or myasthenia gravis
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the clinical response rate of oral nafithromycin compared to combination
of oral amoxicillin-clavulanic acid and azithromycin at the visit on Day 8.
Day 8
Secondary Outcome
Outcome
TimePoints
• To assess the safety of oral nafithromycin treatment.
• To assess the clinical response at early assessment (EA) visit on Day 4.
• To assess the clinical outcome at the follow up (FU) Visit on Day 15.
Day 4, Day 15
Target Sample Size
Total Sample Size="290" Sample Size from India="290" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
29/12/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="6" Days="15"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase III,
open-label, multicentre, comparative, interventional study to evaluate the
efficacy, safety and tolerability of oral Nafithromycin versus combination of
oral Amoxicillin-clavulanic acid and Azithromycin in approximately 290 adult
patients with Acute Bacterial Rhinosinusitis (ABRS). The patients will be
randomized 1:1 such that they receive oral antibiotic treatment for a duration
of 3 days for patients on Nafithromycin 400mg, arm and 5 to 7 days for
Amoxicillin-clavulanic acid 625mg and Azithromycin 500 mg arm, in the
outpatient setting preferably after a meal. ABRS symptoms will be assessed at
Screening/Baseline, Day 4, Day 8 (+1) and 15 (±2).