A clinical trial to study the efficacy and safety of combination drugs of Pregabalin Prolonged Release and Etoricoxib in comparison to single therapy of Etoricoxib in patients having chronic low back pain in India.
- Conditions
- Chronic pain, not elsewhere classified,
- Registration Number
- CTRI/2018/10/015886
- Lead Sponsor
- Sun Pharma Laboratories Limited
- Brief Summary
This is a randomised, multi-centric, open label, parallel group, comparative phase III clinical study to evaluate efficacy and safety of fixed dose combination of Pregabalin prolonged release and Etoricoxib in comparison to monotherapy of Etoricoxib in patients having chronic low back pain. Male or female 272 subjects with age between 18 to 65 years, diagnosed with chronic low back pain for at least 03 months and NRS score of at least 4 will be enrolled in the study. Total study duration of 10 weeks will consist of 4 visits including: one screening visit, one enrolment visit, one follow-up visit and end of the study visit at 08 weeks. Efficacy analysis will be assessed by change in Numeric Rating Scale (NRS), Roland-Morris Disability questionnaire (RDQ), Visual Analog Scale (VAS), Patient Global Impression of Improvement (PGI-I) and Clinical Global Impression of Improvement (CHI-I) from baseline to 08 weeks.
Primary Endpoint(s): Mean change in Numeric Rating Scale (NRS) from enrollment to 8 weeks [Time frame: 08 weeks]
**Secondary Endpoint(s):**
**1.** Mean change in Numeric Rating Scale (NRS) from enrollment to 4 weeks [Time frame: 04 weeks]
**2.** Mean change in Roland-Morris Disability Questionnaire (RDQ) from enrollment [Time frame: 04, 08 weeks]
**3.** Mean change in Visual Analogue Scale (VAS) from enrollment [Time frame: 04, 08 weeks]
**4.** Consumption of rescue medication (total dose of paracetamol tablets consumed) (post enrolment) [Time frame: 04, 08 weeks]
**5.** Patient Global Impression of Improvement (PGI-I) [Time frame: 04, 08 weeks]
**6.** Clinical Global Impression of Improvement (CGI-I) [Time frame: 04, 08 weeks]
**7.** Proportion of participants with adverse events and serious adverse events [Time frame: 08 weeks]
**Discussion and Conclusion:**
This was a phase III, randomized, multi-centric,active controlled, parallel group, open-label, comparativestudy conducted at 12 active sites in 319 patients to evaluate efficacy andsafety of FDCof Pregabalin Prolonged Release and Etoricoxib in comparison to Etoricoxibalone in patients having chronic low back pain. Eligible patients wererandomized to either FDC of Pregabalin Prolonged Release and Etoricoxib orEtoricoxib arm and treatment of once daily was given for eight weeks. Efficacywas assessed by evaluating effect of treatment on pain intensity and functionalstatus by validated scales. For pain intensity NRS and VAS were used whereasfor functional status RDQ was used. Safety was assessed by profile of TEAEs.
**Principal Findings:**This trial demonstrated that treatment with FDC of PregabalinProlonged Release and Etoricoxib had provided superior efficacy than Etoricoxibalone in primary outcome measures such as NRS as well as on secondary outcomemeasures such as RDQ, VAS, PGI-I and CGI-I. It is worthwhile to notethateffect on all these parameters were seen as early as by 28 days. Use of rescuemedication Paracetamol was less in test arm than Comparatorarm. Both study medications were well tolerated and safe in studypopulation.
**Efficacy Data:**
**1. Effect on Pain Intensity Domain:**
An NRS involves asking patients to rate the painfrom 0 to 10 (an 11-point scale). Reduction in the scale suggests improvementin back pain. It is suggested that in chronic low back pain minimum clinicallyimportant change (MCIC) is 2.5. We have observed in our study that change frombaseline at eight weeks was significantly higher (4) in FDC of PregabalinProlonged Release and Etoricoxib arm than both MCIC (2.5) and Etoricoxib arm(2.92). We have seen similar trend in assessment of VAS. In test arm changefrom baseline at eight weeks was significantly higher (37.6 mm) than both MCIC(15 mm) and Comparator arm (28.5 mm). Thus, we can say that our test arm FDC ofPregabalin Prolonged Release and Etoricoxib has demonstrated both clinicallyand statistically significant reduction in NRS and VAS scores both thancomparator arm.
**2. Effect on Functional Status Domain:**
Low back pain interferes withactivities such as mobility, dressing, sitting and standing. Patients can give this information bycompleting disability questionnaires such as Roland–Morris DisabilityQuestionnaire (RDQ). The RDQ focuses on a limited range of physical functions,including walking, bending over, sitting, lying down, dressing, sleeping,self-care and daily activities. The MCIC of the RDQ has been assessed in anumber of studies. It is recommended to consider at least 3.5 as MCIC. We haveobserved that in test arm change from baseline at eight weeks was significantlyhigher (9.28) than both MCIC (3.5) and Comparator arm (6.78). Thus, our testarm FDC of Pregabalin Prolonged Release and Etoricoxib has demonstrated bothclinically and statistically significant reduction in RDQ scale than comparatorarm.
Improvementin NRS, VAS and RDQ can be reflected very well in other secondary outcomeparameters such as PGI-I, CGI-I and consumption of rescue medicationParacetamol. Thus we can say that FDC of Pregabalin Prolonged Release andEtoricoxib has demonstrated both clinically and statistically significanteffect than comparator arm Etoricoxib alone.
**Safety Data:**
We have observed that a total of 19 patients hadatleast one TEAE. Total number of TEAEs in ourstudy were 22. Incidence of TEAEs were 11 (6.9%) in test arm and 8 (5%) in Comparatorarm. Incidence of ADRs were 5 (3.1%) in FDC of Pregabalin Prolonged Release andEtoricoxib and 2 (1.3%) in Etoricoxib arm. Out of total 11 TEAEs,eight were mild in nature and three were moderate in nature in test arm.In Etoricoxib arm, out of total 11 TEAEs, 10 were mild innature and one was moderate in nature. All 22 AEs were recovered/resolved. None of thepatients discontinued from the study due to AE. No serious AEs were reported in thestudy. Therefore, we can conclude that both treatments were safe and welltolerated.
**Implications of study results**Chronic low back pain (LBP) has been shown to be theresult of neuropathic as well as nociceptive pain mechanisms. Based on thisevidence, it has been suggested that anticonvulsants in combination with either opioids, traditionalnonsteroidal anti-inflammatory drugs or muscle relaxants could be useful in thetreatment of this condition. Based on our studyresults we can say that FDC of Pregabalin Prolonged Release and Etoricoxib whengiven once daily for eight weeks in the patients of chronic low back pain canresult into superior reduction in pain intensity and improvement in functionalstatus of patients. Thus, in such patients giving FDC is a better option thangiving Etoricoxib alone.
**Conclusion**Wehave observed in our study that in patients having chronic low back pain whentreated with FDC of Pregabalin Prolonged Release and Etoricoxib experienced astatistically and clinically significant benefit in pain intensity andfunctional status domain than those treated with Etoricoxib alone. Benefitswere seen as early as 28 days. Overall the drug was found to be safe and welltolerated by the patients. Hence, FDC of Pregabalin Prolonged Release andEtoricoxib can be a better therapeutic option than administering Etoricoxibalone in patients with chronic low back pain by producing both better and earlypain relief and improvement in disability.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 272
- 1.Male or female patients of 18 to 65 years of age (both inclusive) 2.Patients with chronic low back pain (symptoms duration: greater than or equal to 3 months) and at least one of the following features on the side corresponding to leg pain: a.Sharp and shooting pain below the knee; b.Pain evoked by straight leg raising to 60 degrees or less; c.Decreased or absent ankle reflex; d.Weakness of muscles below the knee.
- e.Sensory loss in L5/S1 distribution 3.Patient who have pain score of at least 4 on a Numeric Rating Scale (11- point).
- 4.Patients who agree not to use any other approved or experimental pharmacological treatments for low back pain, other than mentioned in the protocol, at any time during the study.
- 5.Patient or his/her legally accepted representative is willing to give informed consent.
- 6.Female participants of childbearing potential must be willing to use acceptable method of contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study.
- Acceptable method of contraception includes (e.g., barrier method with spermicide).
- The "calendar method," withdrawal, or an IUD is NOT an acceptable method.
- 7.Patients willing to follow the study protocol.
- 1.Breast feeding or pregnant females 2.History of Hepatitis B, Hepatitis C or HIV infection 3.Anticonvulsants, antidepressants (eg tricyclic,tetracyclic,atypical),aspirin at doses greater than 81 mg/day,benzodiazepines,opioids,herbal medications,mexiletine HCl,epidural injection and procedure (eg acupuncture)performed within 6 weeks prior to screening or planning to use during the study or taken more than recommended doses of any dosage form of NSAIDs analgesics in last 15 days prior to screening and any treatment for low back pain within 2 days prior to enrolment 4.Patients who,in the opinion of the investigator,have history of clinically significant cardiovascular disease (ex MI),psychiatric disorders as per DSM-5 (Bipolar disorder,generalized anxiety disorder,depression,psychosis or post-traumatic stress disorder),epilepsy or seizure disorder requiring treatment with anti-epileptic drugs,severe hepatic and renal impairment(defined as either creatinine clearance less than 60 mL/min or renal dysfunction requiring hemodialysis),neoplastic disease, suicidal behavior,underlying conditions that may precipitate encephalopathy (ex liver failure),lactose intolerance,angle closure glaucoma,angioedema,urinary retention,thyroid disorder,uncontrolled hypertension and diabetes or abnormal ECG or the participant has any other abnormal laboratory value or MRI lumbosacral spine finding (eg neoplasia) of clinical significance for this study during screening visit 5.5.Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of Pregabalin Prolonged Release or Etoricoxib in the investigators judgment 6.Patients with known alcohol or other substance abuse within last one year as per DSM-5 criteria 7.Participant has hypersensitivity, intolerance, or contraindication to the use of Etoricoxib and Pregabalin, or any of its components 8.HbA1c greater than 8% at screening 9.Patient received treatment with an investigational device or compound within 6 months prior of the screening.
- 10.Patients with clinically significant disorder that, in the opinion of the investigator, would result in the participant’s inability to understand and comply with the requirements of the study 11.Patients operating heavy complex machinery or who intend to drive.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Mean change in Numeric Rating Scale (NRS) from enrolment to 8 weeks Mean change in Numeric Rating Scale (NRS) from enrolment to 8 weeks
- Secondary Outcome Measures
Name Time Method 1.Mean Change in Numeric Rating Scale (NRS) from enrolment to 4 weeks 2.Mean change in Roland-Morris Disability Questionnaire (RDQ) from enrolment
Trial Locations
- Locations (12)
B. J. Government Medical College & Sassoon General Hospitals
🇮🇳Pune, MAHARASHTRA, India
Gandhi Hospital
🇮🇳Hyderabad, TELANGANA, India
Grant Government Medical College and Sir J J group of Hospitals
🇮🇳Mumbai, MAHARASHTRA, India
Hi-Tech Multispeciality Hospital
🇮🇳Gandhinagar, GUJARAT, India
Kanoria Hospital & Research Centre
🇮🇳Gandhinagar, GUJARAT, India
King George’s Medical University
🇮🇳Lucknow, UTTAR PRADESH, India
Kovai Diabetes Speciality Centre and Hospital
🇮🇳Coimbatore, TAMIL NADU, India
Nehru hospital
🇮🇳Chandigarh, CHANDIGARH, India
Osmania General Hospital
🇮🇳Hyderabad, TELANGANA, India
SMS Hospital
🇮🇳Jaipur, RAJASTHAN, India
Scroll for more (2 remaining)B. J. Government Medical College & Sassoon General Hospitals🇮🇳Pune, MAHARASHTRA, IndiaDr Shrinivas Shankar ShintrePrincipal investigator9822053186drssshintre@gmail.com