To Evaluate the Superiority of Fixed Combination (Orfenadrine 35mg, Acetaminophen 325mg, Caffeine 65mg and Diclofenac Sodium 50mg) Compared to Voltaren® (Diclofenac Sodium 50mg) in the Treatment of Acute Postural Low Back Pain.

NCT ID: NCT02985671

Last Updated: 2020-09-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-31
• Study Completion Date: 2021-10-31

Brief Summary

The purpose of this study is to determine whether the fixed combination of orphenadrine, acetaminophen, caffeine and diclofenac sodium is more effective in the treatment of an acute episode of mechanical postural low back pain than Voltaren®. Will be randomized 110 participants of both sexes, aged 18 years or older and less than 65 years of age with an acute episode of mechanical postural low back pain and they will be allocated to one of two treatment groups: Group 1: Fixed combination of orphenadrine, acetaminophen, caffeine and diclofenac sodium; or Group 2: Voltaren®

Detailed Description

The fixed combination of orphenadrine 35mg, acetaminophen 325mg, caffeine 65mg and diclofenac sodium 50mg aims to provide patients with anti-inflammatory, analgesic and myorelaxant action with adequate safety and tolerability profile.

Diclofenac is a nonsteroidal anti-inflammatory with analgesic, anti-inflammatory and antipyretic action and is effective in the treatment of a variety of acute and chronic inflammatory and painful conditions. Its anti-inflammatory effect occurs by inhibiting the synthesis of prostaglandins by inhibiting COX-1 and COX-2 in an equipotent manner.

Orphenadrine, on the other hand, is a central acting muscle relaxant that has analgesic and anticholinergic effects. It presents clinical efficacy in the treatment of painful conditions associated to pictures such as strains and sprains, especially of acute character, among other musculoskeletal conditions that present with pain and muscular contracture.

Concerning acetaminophen, its a drug with analgesic and antipyretic action as well as anti-inflammatory properties. It is widely used in a wide variety of pathologies with a focus on the treatment of mild to moderate pain. It is a non-opioid analgesic with action in the inhibition of cyclooxygenase and consequently in the production of prostaglandins, with potency similar to that of aspirin. It is the analgesic of choice for children, the elderly and pregnant women. It has been used successfully in the treatment of back pain. The association between acetaminophen and orphenadrine is known and clinically effective in analgesia, as well as the combination of acetaminophen and diclofenac, which also provides clinical efficacy in the management of acute postoperative pain.

Lastly, caffeine, an alkaloid belonging to the group of methylxanthines, is an agonist that competes with adenosine receptors, acting in these receptors in very varied areas, such as throughout the peripheral circulation and in the cerebral cortex. Caffeine enhances the effects of other analgesics, improves acetaminophen pharmacokinetics, and induces mood changes. All these mechanisms may contribute to improve the analgesic action of acetaminophen.

The association of non-steroidal anti-inflammatory, muscle relaxant, analgesic and caffeine in the symptomatic treatment of painful conditions associated with the musculoskeletal system is quite old.

Conditions

Postural Low Back Pain; Mechanical Low Back Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental Drug & Voltaren Placebo

Orphenadrine + acetaminophen + caffeine + diclofenac sodium & Placebo of Voltaren

01 tablet of experimental drug (orphenadrine 35mg, acetaminophen 325mg, caffeine 65mg and diclofenac sodium 50mg) + 01 tablet of placebo of Voltaren, to be administrated orally, three times a day, respecting the interval of 08 hours between administrations, during 7 days.

Group Type: EXPERIMENTAL

orphenadrine, acetaminophen, caffeine and diclofenac sodium

Intervention Type: DRUG

orphenadrine 35mg, acetaminophen 325mg, caffeine 65mg and diclofenac sodium 50mg tablet

Placebo (for Voltaren)

Intervention Type: DRUG

tablet without active substances, manufactured to mimic Voltaren 50mg tablet

Voltaren® + Experimental Drug Placebo

Voltaren & Placebo of Orphenadrine + acetaminophen + caffeine + diclofenac sodium

01 tablet of Voltaren + 01 tablet of placebo of experimental drug (orphenadrine, acetaminophen, caffeine and diclofenac sodium), to be administrated orally, three times a day, respecting the interval of 08 hours between administrations, during 7 days.

Group Type: ACTIVE_COMPARATOR

Diclofenac Sodium 50 MG

Intervention Type: DRUG

Voltaren (diclofenac sodium 50mg) tablet

Placebo (for experimental drug)

Intervention Type: DRUG

tablet without active substances, manufactured to mimic experimental product tablet

Interventions

orphenadrine, acetaminophen, caffeine and diclofenac sodium

orphenadrine 35mg, acetaminophen 325mg, caffeine 65mg and diclofenac sodium 50mg tablet

Intervention Type: DRUG

Diclofenac Sodium 50 MG

Voltaren (diclofenac sodium 50mg) tablet

Intervention Type: DRUG

Placebo (for experimental drug)

tablet without active substances, manufactured to mimic experimental product tablet

Intervention Type: DRUG

Placebo (for Voltaren)

tablet without active substances, manufactured to mimic Voltaren 50mg tablet

Intervention Type: DRUG

Other Intervention Names

experimental drug; active comparator; Voltaren; Placebo (for orphenadrine + acetaminophen + caffeine + diclofenac sodium); Placebo (for Voltaren 50mg)

Eligibility Criteria

Inclusion Criteria

1. Ability to understand and consent their participation in this clinical study, expressed by signing the Informed Consent Form (ICF);

2. Patient with acute low back pain who responds to the pain period less than or equal to 3 days and the minimum value of 40 mm in the VAS;

3. Research participants who perform simple RX of lumbosacral spine, with results within the limits of normality for the age group.

Exclusion Criteria

1. Use of illicit drugs;

2. Fertile women who have had a positive pregnancy test in the urine or during gestation or breastfeeding;

3. Participants who present with allergic reaction, asthma or urticaria in response to exposure to aspirin, sulfonamides and other NSAIDs;

4. Women who do not agree to use acceptable contraceptive methods (oral contraceptive, intravenous contraceptive, intrauterine device (IUD), hormonal implant, barrier methods, hormonal transdermal patch and tubal ligation); except for those surgically sterile (bilateral oophorectomy or hysterectomy), menopause for at least one year, and participants who report not engaging in sexual practices or non-reproductive practices;

5. Participants with inflammatory conditions such as any rheumatic condition known as rheumatoid arthritis, osteoarthrosis (grade II, III and IV criteria of Kellgren and Lawrence, Annex IV), ankylosing spondylitis or psoriatic arthritis, chronic pain condition (greater than six weeks), primary or secondary neoplasia, moderate to severe scoliosis (greater than 40º), low back pain as a result of trauma, visceral disorder such as dysmenorrhea or endometriosis;

6. Known hypersensitivity to the components of the medicines used during the study;

7. Research participants who have had bacterial infection recently (last 90 days), affecting the spine, pelvic or abdominal region; as well as participants with a history of bacterial infection that affected the spine in a chronic way;

8. Research participants previously diagnosed with herniated disc, osteoid osteoma, arthroscopic narrowing of the spinal canal, spondyloarthropathies, spondylodiscites, renal calculus, calculitic cholecystitis, endometriosis, prostatitis, abdominal aortic aneurysm, chronic pelvic pain, pyelonephritis, perirenal abscesses and pancreatitis , rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica, gout, episodes of acute monoarthritis compatible with pseudogout, Paget's disease, septic arthritis, avascular necrosis, Wilson's disease, hemochromatosis, alkaptonuria, primary osteochondromatosis, iritis, colitis, urethritis and skin rash;

9. Participants who present suspected or previous history of esophageal, gastric or duodenal ulcers, or bleeding before the first dose of study medication;

10. Research participants presenting with any chronic uncontrolled disease, such as diabetes, hypertension, chronic hepatic or renal disorders, or any clinical condition that, in the opinion of the investigator, may interfere with the study drug;

11. Participants presenting with inflammatory bowel disorders (eg, Crohn's disease or ulcerative colitis), significant coagulation defect or history of cardiovascular disease that may prevent the use of NSAIDs, such as congestive heart failure;

12. Any finding of clinical observation (clinical / physical assessment) that is interpreted by the investigating physician as a risk to the participation of the research participant in the clinical study;

13. History of lumbar spine surgery, of any nature;

14. Failure to understand and respond to the Roland Morris questionnaire, SF-36 quality of life questionnaire, and Participant's diary, and who do not have an accompanying person to assist him / her;

15. Participant with a history of malignant disease without documentation of remission / cure, eg, melanoma, leukemia, lymphoma, myeloproliferative diseases and renal cell carcinoma of any duration should be excluded;

16. Immunosuppressed participants;

17. Research participants who perform treatment for osteoporosis;

18. Diagnosis of equine cauda syndrome and / or acute severe neurological deficit (presence of motor or sensory changes in the lower limbs and positive Lasegue signal> 60o). Sphincter and anesthesia changes in saddle;

19. History of intense pain at minimal effort, progressive pain and night and persistent restriction of movement;

20. Research participants with unexplained weight loss (more than 10kg in three months);

21. Research participants who are performing some type of oral, physical or topical treatment for low back pain (eg acupuncture, local heat and yoga) and / or initiation of physiotherapy program in the last 2 months before the start of the study;

22. Participant in research that has participated in clinical study protocols in the last 12 (twelve) months (CNS Resolution 251, August 7, 1997, item III, subitem J), unless the investigator deems that there may be direct benefit To the same;

23. Use of prohibited drugs specified in item 11.2 of this protocol. If the participant makes use of acetylsalicylic acid, used as antiplatelet agent, the maximum dose of 200mg will be allowed;

24. Participant who has a relationship of kinship to second degree or bond with employees or employees of Sponsor and Research Center.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ache Laboratorios Farmaceuticos S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mauro C Junior, M.D.

Role: PRINCIPAL_INVESTIGATOR

Allergisa Search Dermato Cosmetic Ltda.

Morton A Scheinberg, M.D.

Role: PRINCIPAL_INVESTIGATOR

AACD - Association of Assistance to the Disabled Child

Pedro Henrique I Pohl, M.D.

Role: PRINCIPAL_INVESTIGATOR

Center for Multidisciplinary Studies CEPES

Pérola G Plapler, M.D.

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Center IOT HCFMUSP

Suely S Roizenblatt

Role: PRINCIPAL_INVESTIGATOR

CDEC Brazil - Center for the Development of Clinical Studies Brazil

Central Contacts

Elisangela C Rorato, Specialist

Role: CONTACT

elisangela.rorato@ache.com.br

+55 11 2608-6130

Maria Fernanda A Giacomin, M.D.

Role: CONTACT

maria.giacomin@ache.com.br

+55 11 2608-8292

Other Identifiers

ACH-TND-03(12/14)

Identifier Type: -

Identifier Source: org_study_id