Study Evaluating Dexketoprofen Trometamol/Tramadol Hydrochloride Analgesic Efficacy in Acute Low Back Pain

A randomized, double-blind, study to evaluate the analgesic efficacy and safety of Dexketoprofen trometamol and Tramadol hydrochloride combination versus placebo on moderate to severe acute pain in patients with acute low back pain.

This is a multicenter, randomized, double-blind, double-dummy, parallel group, placebo-controlled study encompassing 2 study phases: a single-dose phase (first 8 hours) and a multiple-dose phase starting after the single-dose phase (from 8h until day 5).

Study population will be of male or female patients aged 18 years to 65 years with acute low back pain of moderate to severe intensity, whose onset of the current acute low back pain episode is within 48 hours prior to Screening. Patients with or without radiculopathy will be included, excluding those with neurological signs, according to the Quebec Task Force classification. Patients experiencing a new episode of low back pain will be eligible only if preceded by a period of at least 2 months without any low back pain. Patients should be free from analgesic due to previously administered pain killer (immediate or slow release formulations), according to exclusion criteria.

Approximately 612 patients will be screened to achieve 510 patients randomly assigned to study treatment.

In the single-dose phase patients will receive a single-dose treatment, consisting of 1 film-coated tablet and 2 capsules which have to be orally administered together at the same time (Day 1). The multiple-dose phase will begin 8 hours after the first dose. The patients assigned to Dexketoprofen/Tramadol fixed combination or Tramadol 100 milligram (mg) during the single-dose phase will continue to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase will either receive Dexketoprofen/Tramadol fixed combination or Tramadol 100 mg during the multiple-dose phase.

Eligibility Criteria:
Inclusion Criteria:

1. Properly executed written informed consent.
2. Male or female patients aged 18 years to 65 years.
3. Patients with acute low back reporting pain of at least moderate intensity at Screening (NRS score ≥ 5). The onset of the current acute low back pain episode is within 48 hours prior to Screening.
4. Patients with or without radiculopathy will be included, excluding those with neurological signs, according to the Quebec Task Force classification.
5. Naïve patients to any low back pain or patients with previous history of low back pain experiencing a new episode, preceded by a period of at least 2 months without any low back pain prior to Screening.
6. Patients free from analgesic (as per exclusion criterion 14) due to previously administered pain killer (immediate or slow release formulations), according to physician's judgment.
7. Females participating in the study must be either:

   * Females of non childbearing potential, defined as any woman who had undergone surgical sterilization (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or is more than 2 years post menopausal (defined as no menses for 12 months);
   * Females of childbearing potential (following menarche until menopause unless permanently sterile) provided that they have a negative pregnancy test at Screening and are routinely using an effective method of birth control resulting in a low failure rate (ie, combined hormonal contraception, intrauterine device, condoms in combination with a spermicidal cream, male partner sterilization (vasectomy), bilateral tubal occlusion or total sexual abstinence) during the study treatment.
8. Mentally competent and able to understand and give written informed consent prior to Screening.
9. Compliant to undergo all visits and procedures scheduled in the Study.

Exclusion Criteria:

1. Patients who are judged by the Investigator not to be suitable candidates for the study treatments and the Rescue Medication (RM) based on their medical history, physical examination, Concomitant Medication (CM) and concurrent systemic diseases.
2. Clinically significant abnormalities in the vital signs as per Investigator's judgment.
3. Patients with acute low back pain and radiation to limb with presence of neurologic signs (focal weakness, asymmetry of reflexes, sensory loss in a dermatome, or loss of bowel, bladder, or sexual function) according to Quebec Task Force Classification.
4. History of hypersensitivity to the study treatments, RM or to any other nonsteroidal anti-inflammatory drugs (NSAIDs), or opioids.
5. Known photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.
6. History of peptic ulcer, gastrointestinal disorders when taking NSAIDs, gastrointestinal bleeding, or other active bleeding.
7. History of allergy (eg, precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic oedema) to the study treatments, RM or to any other NSAIDs, or opioids.
8. Anamnestic mild to severe renal dysfunction, mild to severe hepatic dysfunction, as per Investigator's judgment.
9. Patients with chronic dyspepsia.
10. Patients with severe heart failure \[Class III and Class IV of New York Heart Association (NYHA) Classification\].
11. History of hemorrhagic diathesis and other coagulation disorders.
12. History of or current epilepsy or convulsions.
13. Patients with Crohn's disease or ulcerative colitis.
14. Patients receiving monoamine oxidase (MAO) inhibitors (a minimum of 14 days of washout must elapse prior to the Screening).
15. Treatment with topical preparations/medications within 4 hours prior to Screening, anesthetics and muscle relaxants within 8 hours prior to Screening, short-acting analgesics (eg, paracetamol) within 4 hours prior to Screening, other analgesics within 5 half-lives prior to Screening or use of an opioid within the 14 days preceding Screening.
16. Treatment with high doses of salicylates (≥3 g/day), anticoagulants, thrombolytic and antiplatelet agents, heparins, corticosteroids (except inhalers and topical agents), lithium methotrexate, used at high doses of 15 mg/week or more, hydantoins (including phenytoin) and sulphonamides, antiepileptics, antipsychotics, serotonin reuptake inhibitors and tricyclic antidepressants, and analgesics within 48 hours or 5 half-lives (whichever is the longer) prior to Screening.
17. Patients using sedatives (eg, benzodiazepines) and hypnotic agents within 8 hours before Screening.
18. Any chronic or acute painful condition other than the study indication that may interfere with the assessment of the efficacy of the study treatment.
19. Any non-pharmacological interventional therapy for low back pain (physical therapy, acupuncture, massage etc.) one month before Screening.
20. Patients with litigation related to work.
21. Patients with severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake) within one month prior to Screening.
22. Severe respiratory depression according to physician's judgment.
23. Participation in other clinical studies in the previous 4 weeks.
24. History of drug or alcohol abuse. For the purpose of the study, alcohol abuse is defined as regularly intake of more than 4 units of alcohol per day (1 unit corresponds approximately to 125 ml wine, 200 ml beer, 25 ml spirit).
25. History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study.
26. Pregnant and breastfeeding women: a pregnancy test will be performed on all women of childbearing potential at Screening.
27. Patients presenting any of the contraindications reported for dexketoprofen/tramadol, tramadol or paracetamol (according to the SmPC).
28. Known or suspected serious spinal pathology (eg, metastatic, inflammatory or infective diseases of the spine, cauda equine syndrome, trauma, spinal fracture).
29. Spinal surgery within the preceding 6 months.