CTRI/2019/03/018143 [Registered on: 18/03/2019] Trial Registered Prospectively
Last Modified On:
04/03/2020
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A Clinical Study to evaluate Efficacy and Safety of Tapentadol Nasal Spray in Comparison to Tramadol in Patients with Post-Operative Pain
Scientific Title of Study
A Multicentric, Randomized, Open Label Clinical Trial to Evaluate Efficacy and Safety of Tapentadol Nasal Spray in Comparison to Tramadol Immediate Release Capsule and Intravenous Injection in Patients with Post-Operative Moderate to Severe Pain
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CT/TAPE/PAIN/17/03 Version 2.1 21/12/2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sanjay Sharma
Designation
General Manager
Affiliation
Torrent Pharmaceuticals Ltd, Research Centre
Address
Torrent Pharmaceuticals Ltd, Research Centre, Village: Bhat
Dist: Gandhinagar, Gujarat 382428 India
Ahmadabad GUJARAT 382428 India
Phone
079-23969100
Fax
079-23969135
Email
SanjaySharma@torrentpharma.com
Details of Contact Person Scientific Query
Name
Dr Sanjay Sharma
Designation
General Manager
Affiliation
Torrent Pharmaceuticals Ltd, Research Centre
Address
Torrent Pharmaceuticals Ltd, Research Centre, Village: Bhat
Dist: Gandhinagar, Gujarat 382428 India
Ahmadabad GUJARAT 382428 India
Phone
079-23969100
Fax
079-23969135
Email
SanjaySharma@torrentpharma.com
Details of Contact Person Public Query
Name
Dr Sanjay Sharma
Designation
General Manager
Affiliation
Torrent Pharmaceuticals Ltd, Research Centre
Address
Torrent Pharmaceuticals Ltd, Research Centre, Village: Bhat
Dist: Gandhinagar, Gujarat 382428 India
Ahmadabad GUJARAT 382428 India
Phone
079-23969100
Fax
079-23969135
Email
SanjaySharma@torrentpharma.com
Source of Monetary or Material Support
Torrent Pharmaceutical Ltd., India
Primary Sponsor
Name
Torrent Pharmaceutical Ltd
Address
Torrent Pharmaceuticals Ltd, Research Centre, Village: Bhat
Dist: Gandhinagar, Gujarat 382428 India
NKPSIMS and Lata Mangeshkar Hospital, Digdoh hills, Hingna Road, Nagpur-440019, Maharashtra, India Nagpur MAHARASHTRA
9422108284
drshmankar@gmail.com
Dr Rohit Luthra
Noble Hospital
Clinical researcch department, Basement Noble Hospital Annexe, Noble Hospital, 153, Magarpatta City Road, Hadapsar, Pune-411013 Pune MAHARASHTRA
99239875502
dr.rohitluthra@gmail.com
Dr D Prasada Rao
Rajiv Gandhi Institute of Medical Sciences & RIMS, Government General Hospital
Department of Surgery, Rajiv Gandhi Institute of Medical Sciences & RIMS, Government General Hospital, Srikakulam-532001, Andhra Pradesh, India Srikakulam ANDHRA PRADESH
9849702720
drprasadaraod@gmail.com
Dr Hemant Lalitchandra Leuva
Sheth V S General Hospital & Smt. N.H.L. Municipal Medical College
Department of General Surgery, Sheth V S General Hospital & Smt. N.H.L. Municipal Medical College, Ellisbridge, Ahmedabad-380006, Gujarat, India. Ahmadabad GUJARAT
9427323050
drhemantleuva@gmail.com
Dr Bikram Kumar Gupta
Sir Sunderlal Hospital, Institute of Medical Science - Banaras Hindu University
Department of Anasthesiology, Sir Sunderlal Hospital, Institute of Medical Science - Banaras Hindu University, Varanasi, 221005, Uttar Pradesh-221005, India. Varanasi UTTAR PRADESH
8400100128
bikramgupta03@gmail.com
Dr Ranajit Panigrahi
Sparsh Hospital and Critical Care
Orthopedic OPD, Sparsh Hospital and Critical Care (P), Ltd , Plot No.A/407, Sahid Nagar, Bhubaneswar -751007 Khordha ORISSA
9777037435
ranajitpanigrahi@gmail.com
Dr T Arulappan
Sri Ramachandra Hospital
Dept. Gen Surgery, No.1, Ramachandra Nagar, Porur, Chennai-600116 Chennai TAMIL NADU
9841215453
arulappant@gmail.com
Dr Prafulla Borkar
Vidarbha Institute of Medical Sciences (VIMS)
5 floor, clinical research department, Vidarbha Institute of Medical Sciences (VIMS), Near LIC Square, Mohan Nagar, Kamptee Road, Nagpur-440001 Nagpur MAHARASHTRA
Nasal Spray 22.5 mg/45 mg every 4-6 hours for 05 days
Comparator Agent
Tramadol
Injection 50mg/100mg every 4-6 hours for 1 day or 2 day
Capsule 50mg/100mg every 4-6 hours for remaining 03/04 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female subjects of 18-65 years of age, both inclusive.
2. Patient is fit for surgery under general anaesthesia or regional anaesthesia
3. Patients having physical status of I-II according to American Society of Anaesthesiologists (ASA) classification.
4. After weaning of anaesthesia post-surgery, patients having pain intensity score ≥ 4 on an 11-point (0 to 10) Numeric
Pain Rating Scale (NPRS).
5. Patient willing to remain hospitalized for a minimum of 5 days post-surgery.
6. Patient willing to give written informed consent to participate in the study before undergoing surgical intervention.
ExclusionCriteria
Details
1. Patients with a history of hypersensitivity to Tapentadol or Tramadol.
2. History of active or suspected gastrointestinal ulcers or bleeding or motility disorder within the past 6 months prior to screening.
3. Patient who will undergo either laparoscopic surgeries (eg. laparoscopic cholecystectomy, laparoscopic appendectomy) or cardiothoracic surgeries (eg. heart bypass surgery, open esophagectomy) or cancer surgeries (eg. mastectomy).
4. Patients who have taken any medication by intranasal route within the past 72 hours prior to randomization.
5. Patients who have received analgesic postoperatively prior to
randomization.
6. Patients with chronic use of any opioids for any disease within the last 28 days prior to screening.
7. Patients currently being treated with tricyclic antidepressants, selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors, anticonvulsants, neuroleptics, triptans, monoamine oxidase inhibitors, steroids or other drugs that has potential to reduce the seizure threshold within the past 4 weeks prior to screening.
8. Patients having clinically significant postoperative complications before randomization which may compromise safety of the patient or study outcome as per investigator opinion.
9. History of any seizure disorder or epilepsy.
10. Patients with history of mild to moderate traumatic brain injury (loss of consciousness ≥ 30 minutes to 6 hours), stroke or brain neoplasm within past 1-year or severe traumatic brain injury (loss of consciousness ≥ 6 hours) within past 15
years prior to screening.
11. Patients with clinically significant ECG abnormalities or QTc ≥ 450 msec for male or QT ≥ 470 msec for female at screening.
12. Any clinically significant abnormal nasal or respiratory tract conditions i.e., atrophic rhinitis, nasal polyp, upper respiratory tract infection etc. which can interfere with the absorption of the drug.
13. History of drug abuse or known active alcohol abuse within past 6 months.
14. Patients with liver enzymes (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase) > 2.5X the upper limit of normal value (ULN) or total bilirubin >1.5X of ULN or serum creatinine >1.5X of ULN at screening.
15. Patients having respiratory rate less than 12 breaths per minute or greater than 20 breaths per minute at randomization.
16. History of active Hepatitis B or Hepatitis C or HIV infection.
17. Pregnant or lactating women.
18. In the opinion of the investigator, patient is either unable to cooperate or unlikely to adhere with any study procedures.
19. Patients who have participated in any other investigational drug trial within the past four weeks prior to screening.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
1. Pain intensity difference
2. Patient Global Assessment
3. Sum of Pain Intensity Difference
1. Pain intensity difference at 60 minutes
2. Patient Global Assessment at 24 hours
3. Sum of Pain Intensity Difference at 60 minutes
Secondary Outcome
Outcome
TimePoints
1. Sum of Pain Intensity Difference
2. Meaningful pain relief
3. Total pain relief score
4. First intake of rescue medication for pain
5. Percentage of patients who required rescue medication for nausea and
vomiting
6. Pain intensity difference
7. Patient global assessment
1. Sum of Pain Intensity Difference at 2 hrs, 4 hrs, 24 hrs, 48 hrs, 72 hrs,
96 hrs and 120 hours
2. Median Time to onset of meaningful pain relief
3. Total pain relief score at at 24 hrs, 48 hrs, 72 hrs, 96 hrs and 120
4. Median time to first intake of rescue medication for pain
5. NA
6. Pain intensity difference at pre-2nd dose and pre-3rd dose
7. Patient global assessment at 120 hours
Target Sample Size
Total Sample Size="294" Sample Size from India="294" Final Enrollment numbers achieved (Total)= "294" Final Enrollment numbers achieved (India)="294"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Tapentadol is centrally acting analgesic
with dual mechanisms of action: µ-opioid receptor agonism and norepinephrine
reuptake inhibition. It is approved as immediate release tablet (50mg, 75 mg,
100mg) and extended release tablet (50mg, 100mg, 150mg, 200mg, 250mg) in India
for moderate to severe acute pain. In phase I studies conducted in
healthy volunteers, Tapentadol nasal spray has been found safe and
well-tolerated without any serious adverse events. The objectives of this Phase III study are to evaluate the efficacy and safety of Tapentadol nasal spray in comparison
to Tramadol immediate release tablet and intravenous injection in patients with
post-operative moderate to severe pain.