CTRI/2022/01/039128 [Registered on: 04/01/2022] Trial Registered Prospectively
Last Modified On:
10/12/2021
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
Phase-III clinical trial of Tapentadol Nasal Spray in comparision with Tramadol
Scientific Title of Study
A Multi-centric, Randomized, Double-blind, Double-dummy Clinical
Trial to Evaluate Efficacy and Safety of Tapentadol Nasal Spray in Comparison to
Tramadol in Patients With Acute Moderate to Severe Pain
Trial Acronym
Tape NS
Secondary IDs if Any
Secondary ID
Identifier
CT/TAPE/PAIN/21/03_02 version no.03 Date:15.07.21
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
DrRam Gupta
Designation
Assistant General Manager
Affiliation
Torrent Pharmaceuticals Limited
Address
Clinical Research Department, Old building, second floor,Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Clinical Research Department, Old building, second floor,Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Gandhinagar GUJARAT 382428 India
Phone
07923969100-197
Fax
07923969135
Email
ramgupta@torrentpharma.com
Details of Contact Person Scientific Query
Name
DrBhumika Ahir
Designation
Manager
Affiliation
Torrent Pharmaceuticals Limited
Address
Clinical Research Department, Old building, second floor Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Clinical Research Department, Old building, second floor Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Gandhinagar GUJARAT 382428 India
Phone
07923969100-162
Fax
07923969135
Email
bhumikaahir@torrentpharma.com
Details of Contact Person Public Query
Name
DrRam Gupta
Designation
Assistant General Manager
Affiliation
Torrent Pharmaceuticals Limited
Address
Clinical Research Department, Old building, second floor,Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Clinical Research Department, Old building, second floor, Torrent Pharmaceuticals Limited
Research Centre, Village Bhat, Dist. Gandhinagar - 382 428
Gujarat, India Gandhinagar GUJARAT 382428 India
Phone
07923969100-197
Fax
07923969135
Email
ramgupta@torrentpharma.com
Source of Monetary or Material Support
Torrent Pharmaceuticals Limited
Primary Sponsor
Name
Torrent Pharmaceuticals Limited
Address
Research Centre,Village Bhat, Dist Gandhinagar 382428 Gujarat India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
DrValsammaAbraham
Christian Medical College (CMC) Hospital, Punjab
Christian Medical College (CMC) Hospital,
Department of Anasthesiology,
Brown Road, Ludhiana - 141008, Punjab, India
Ludhiana PUNJAB
911612115376 911612609958 contact@cmcludhiana.in
DrSunilShetty
D Y Patil Medical College
D Y Patil Medical College
Sector 5 Nerul Navi Mumbai Maharashtra - 400706 India
Mumbai (Suburban) MAHARASHTRA
02227735999 02227736038 dyphrcms@gmail.com
DrAnilDhule
Government Medical College,Aurangabad
Government Medical College,
Near Panchakki Road.
Aurangabad, Maharashtra Pin: 431001, India
Aurangabad MAHARASHTRA
02402402418 02402402418 dranildhule5@gmail.com
Dr Ashish Sethi
International Gastro Institute Vadodara
International Gastro Institute
Isha Hospital, Behind Atlantis Opp. Vadodara Central Sarabhai Campus, Subhanpura, Vadodara, Vadodara GUJARAT
02652314055 02652314055 drashishsethi@hotmail.com
DrKRBhagawan
K. S. Hegde Medical College karnataka
K S Hegde Medical Academy,
P.O Deralakatte,
Mangaluru - 575018
Karnataka, India
Dakshina Kannada KARNATAKA
08242204490 08242204490 dean.kshema@nitte.edu.in
DrSushil Mankar
NKPSIMS and Lata Mangeshkar Hospital Nagpur
NKPSIMS and Lata Mangeshkar Hospital,
Digdoh Hills, Hingna Road,
Nagpur-440019, Maharashtra, India
Nagpur MAHARASHTRA
07104665000 07104665011 nkpsims1@rediffmail.com
DrSurajKumarPattnayak
Rajiv Gandhi Institute of Medical Sciences and RIMS Govt. General Hospital
Rajiv Gandhi Institute of Medical Sciences and RIMS Govt. General Hospital,
Research Wing, 2nd Floor,
Beside FM Ward, Srikakulam-532001 , A.P Srikakulam ANDHRA PRADESH
919000268524 918942279033 rimsresearch@gmail.com
DrTapanShah
Sangini Hospital Gujarat
Sangini Hospital
1st Floor, Santorini Square, Opp. Star Bazzar
Satellite, Ahmedabad-380015, Gujarat, India
Ahmadabad GUJARAT
Patients randomized to the reference arm will be administered tramadol 100 mg i.v as initial
bolus dose. Subsequently, either tramadol 50 mg or 100 mg will be administered
intravenously slowly over 2-3 minutes (4-6 hourly) for first 24 hours, following which
patient will be switched to oral tramadol (50/100 mg) as per the Investigator’s discretion at
every 4-6 hours. Frequency, dosing regimen, dose titration for tramadol in reference arm
would be carried out as per Investigators discretion. Total daily dose of tramadol should not
be more than 400 mg. Placebo of nasal spray will be given at each administration along with tramadol i.v./oral.
Total study treatment duration should not exceed more than 120 hours.
Comparator Agent
Test arm
Patients randomized to test arm will be administered tapentadol nasal spray 45 mg (one spray
in each nostril) every 4-6 hours. Placebo of tramadol injection will be given at treatment initiation and subsequently at an interval of every 4-6 hours for first 24 hours, followed by
placebo of tramadol capsule every 4-6 hours along with tapentadol nasal spray.
Pain intensity will be recorded at baseline, 60 min and then every 24 hours after first
tapentadol nasal spray 45 mg dose administration until the end of the treatment. Depending
on the Investigators assessment of the need for analgesia, the dose of tapentadol nasal spray
may be titrated between 45 mg or 22.5 mg. The frequency of administration of tapentadol
nasal spray will be every 4-6 hourly. Daily total dose greater than 270 mg per days is not recommended.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Acute pancreatitis:
2. Male or female subjects of 18-65 years of age, both inclusive.
3. Patient willing to give written informed consent to participate in the study
Patient diagnosed with acute pancreatitis based on the revised Atlanta Classification
2012 i.e., acute pancreatitis established by two of the following three criteria: (1)
abdominal pain consistent with acute pancreatitis; (2) serum lipase activity (or amylase
activity) at least three times greater than the upper limit of normal; and (3)
characteristic findings of acute pancreatitis on imaging. If the diagnosis of acute
pancreatitis is established by abdominal pain and by increases in the serum pancreatic
enzyme activities, imaging is not mandatory to establish the diagnosis in the emergency
room or on admission to the hospital.
5. Patient complaining of abdominal pain consistent with acute pancreatitis for duration
not more than 24 hours.
6. Patient having NPRS≥5 on an 11-point (0 to 10) Numeric Pain Rating Scale (NPRS),
even after administration of acetaminophen or NSAID.
7. Patient requiring treatment with opioid analgesic in the opinion of Investigator
Lumbago :
1. Male or female subjects of 18-65 years of age, both inclusive.
2. Patient willing to give written informed consent to participate in the study.
3. Low back pain, localized below the costal margin and above the inferior gluteal folds.
4. Patients diagnosed with episode of nonspecific acute lumbago since not more than 2
days prior to inclusion in the trial and more than 6 weeks after the last episode of acute
low back pain.
5. Patient having NPRS≥5 on an 11-point (0 to 10) Numeric Pain Rating Scale (NPRS),
even after administration of acetaminophen or NSAID.
6. Patient requiring treatment with opioid analgesic in the opinion of Investigator.
Trauma :
1. Male or female subjects of 18-65 years of age, both inclusive.
2. Patient willing to give written informed consent to participate in the study.
3. Patient with clinical diagnosis for a musculoskeletal trauma due to traumatic injury of
musculoskeletal structure of limbs like fractures, sprain, tendon rupture.
4. Patient has chief complaint of musculoskeletal pain lasting not more than 2 days prior
to inclusion in the trial.
5. Patient having NPRS≥5 on an 11-point (0 to 10) Numeric Pain Rating Scale (NPRS),
even after administration of acetaminophen or NSAID.
6. Patient requiring treatment with opioid analgesic in the opinion of Investigator
ExclusionCriteria
Details
1.Patients with history of hypersensitivity to tapentadol, tramadol or any of the
excipients.
History of active or suspected gastrointestinal ulcers or bleeding or motility disorder
within the past 6 months prior to screening.
Note: Investigator based on clinical judgement may initiate treatment without waiting
for confirmatory lab reports; however, if the patient is confirmed for meeting any
exclusion criteria based on laboratory results, patient would be withdrawn from study
and will be replaced with another eligible patient
3. Patients who have taken any medication by intranasal route within the past 72 hours
prior to randomization.
4. Patients with chronic use of any opioids for any disease within the last 28 days prior to
screening.
5. 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 have
the potential to reduce the seizure threshold within the past 4 weeks prior to screening.
6. History of any seizure disorder or epilepsy. Patients with increased intracranial
pressure, brain tumors, head injury, or impaired consciousness.
7. Patients with clinically significant ECG abnormalities.
8. 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.
9. History of drug abuse or known active alcohol abuse within the past 6 months.
10. 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, and considered clinically significant by Investigator.
Patients having respiratory rate less than 12 breaths per minute or greater than 20
breaths per minute at randomization.
12. History of active Hepatitis B or Hepatitis C or HIV infection.
13. Pregnant or lactating women or females of childbearing potential, who are neither
surgically sterilized nor willing to use reliable contraceptive methods throughout the
study duration or male subjects of childbearing potential not willing to use reliable
contraception methods throughout the study duration.
14. In the opinion of the Investigator, patient is either unable to cooperate or unlikely to
adhere with any study procedures.
15. Patients who have participated in any other investigational drug trial within the past
four weeks prior to screening.
16. Evidence of obstructive pancreatitis on available cross-sectional imaging.
17. Patients admitted to the Intensive Care Unit (ICU).
18. Patient requiring urgent surgery within 6 days of randomization.
19. Patient with evidence of chronic pancreatitis (recurrent, obstructive and chronic;
autoimmune and chronic; marked pancreatic insufficiency such as steatorrhea).
20. Suspected organ failure or progressing towards organ failure in the opinion of the
Investigator.
21.History of chronic low back pain.
22.Evidence of clinically unstable disease, as determined by medical history, physical
examination, that, in the Investigator opinion, preclude entry into the study
Note-Investigator based on clinical judgement may initiate treatment without waiting
for confirmatory lab reports; however, if the patient is confirmed for meeting any
exclusion criteria based on laboratory results, patient would be withdrawn from study
and will be replaced with another eligible patient
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
1. Pain intensity difference (PID) at 60 minutes from baseline after administering the
first dose of tapentadol nasal spray or tramadol.
2. Patient global assessment at 120 hours/end of treatment
1. Pain intensity difference (PID) at 60 minutes from baseline after administering the
first dose of tapentadol nasal spray or tramadol.
2. Patient global assessment at 120 hours/end of treatment
Secondary Outcome
Outcome
TimePoints
1) Sum of Pain Intensity Difference (SPID) every 24 hours till the end of the treatment.
2) Proportion of patients achieving 30% and 50% reduction in pain intensity from baseline.
3) Time to onset of meaningful pain relief after first dose (Day 0) administration.
4)Time to the first intake of rescue medication for pain.
5) Patient global assessment at 24 hours.
comparison to the tramadol in patients with acute moderate to severe pain
at 24 hours till end of the treatment
Target Sample Size
Total Sample Size="370" Sample Size from India="370" 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)
01/06/2022
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="2" Months="6" Days="25"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Nil
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The efficacy and tolerability of tapentadol oral formulation is well
established in pain management.
Immediate release formulation of tapentadol has been approved by the
US Food and Drug Administration since November 2008 and indicated
for the management of acute pain severe enough to require an opioid
analgesic and for which alternative treatments are inadequate.
Subsequently extended-release formulation was approved by the US
Food and Drug Administration in August 2011 for the management of (a)
pain severe enough to require daily, around-the-clock, long-term opioid
treatment and for which alternative treatment options are inadequate and
(b) neuropathic pain associated with diabetic peripheral neuropathy in
adults severe enough to require daily, around-the-clock, long-term opioid
treatment and for which alternative treatment options are inadequate.
The tapentadol oral solution (20 mg per mL) was also approved by US
Food and Drug Administration in 2012 with the same indication as
tapentadol IR formulation.
CDSCO has approved tapentadol immediate release tablet for relief of
moderate to severe acute pain in adults and extended-release tablet for
use in in-patients under hospital setting for severe acute pain for a period
not exceeding 5 days.
The tapentadol nasal spray has been recently approved by the CDSCO in
2020 and indicated for the treatment of moderate to severe post-operative
pain in hospital admitted patients.
Tapentadol efficacy in alleviating pain is well established. During phase I
study, intra-nasal route showed higher bioavailability and early Tmax as
compared to oral route.
A phase-III, multi-centric, randomized, open-label clinical trial was
conducted to evaluate the 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.
This study established that tapentadol nasal spray is non-inferior to
tramadol IV and Oral. Tapentadol nasal spray provided same degree of
postoperative pain relief in comparison to tramadol IV or oral.
Tapentadol nasal spray was well tolerated. No SAEs were observed and
most AEs observed were mild in nature.
These results support the use of tapentadol nasal spray as a potential
treatment for acute pain.
Since, tapentadol act on pain receptor and alter pain perception without
altering the pathology responsible for pain and tapentadol immediate
release formulation is already approved for acute pain, tapentadol nasal
spray, which is an immediate release formulation to be administered by
nasal route, is expected to alleviate acute moderate to severe pain seen in
hospital settings as emergency department, trauma centre and outpatient
department.
Thus, the current phase III study is planned to evaluate efficacy and
safety of tapentadol nasal spray in comparison to tramadol intravenous
injection and/or immediate release capsule in patients with acute
moderate to severe pain due to acute pancreatitis, acute lumbago and