A Multi-centric, Randomized, Double-blind, Double-dummy ClinicalTrial to Evaluate Efficacy and Safety of Tapentadol Nasal Spray in Comparison toTramadol in Patients With Acute Moderate to Severe Pain
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 370
- 试验地点
- 10
- 主要终点
- first dose of tapentadol nasal spray or tramadol.
研究概览
简要总结
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
trauma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Acute pancreatitis:
- •Male or female subjects of 18-65 years of age, both inclusive.
- •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.
- •Patient complaining of abdominal pain consistent with acute pancreatitis for duration not more than 24 hours.
- •Patient having NPRS≥5 on an 11-point (0 to 10) Numeric Pain Rating Scale (NPRS), even after administration of acetaminophen or NSAID.
- •Patient requiring treatment with opioid analgesic in the opinion of Investigator Lumbago :
- •Patient willing to give written informed consent to participate in the study.
- •Low back pain, localized below the costal margin and above the inferior gluteal folds.
- •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.
- •Patient with clinical diagnosis for a musculoskeletal trauma due to traumatic injury of musculoskeletal structure of limbs like fractures, sprain, tendon rupture.
- •Patient has chief complaint of musculoskeletal pain lasting not more than 2 days prior to inclusion in the trial.
排除标准
- •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
- •Patients who have taken any medication by intranasal route within the past 72 hours prior to randomization.
- •Patients with chronic use of any opioids for any disease within the last 28 days prior to screening.
- •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.
- •History of any seizure disorder or epilepsy.
- •Patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness.
- •Patients with clinically significant ECG abnormalities.
- •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.
- •History of drug abuse or known active alcohol abuse within the past 6 months.
- •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.
- •History of active Hepatitis B or Hepatitis C or HIV infection.
- •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.
- •In the opinion of the Investigator, patient is either unable to cooperate or unlikely to adhere with any study procedures.
- •Patients who have participated in any other investigational drug trial within the past four weeks prior to screening.
- •Evidence of obstructive pancreatitis on available cross-sectional imaging.
- •Patients admitted to the Intensive Care Unit (ICU).
- •Patient requiring urgent surgery within 6 days of randomization.
- •Patient with evidence of chronic pancreatitis (recurrent, obstructive and chronic; autoimmune and chronic; marked pancreatic insufficiency such as steatorrhea).
- •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.
结局指标
主要结局
first dose of tapentadol nasal spray or tramadol.
时间窗: 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
2. Patient global assessment at 120 hours/end of treatment
时间窗: 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
时间窗: 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
次要结局
- 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.)