Efficacy and Safety of Pregabalin/Tramadol Combination Versus Pregabalin in Acute Pain of Neuropathic Origin

NCT05324059 | Completed Phase 3

• 1 other identifier: SIL-30901-III-21 (2)
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Phase IIIb confirmatory study of efficacy and safety, longitudinal, multicenter, randomized, double-blind study of the combination Pregabalin/Tramadol versus Pregabalin in the management of acute pain of neuropathic origin.

Conditions

Neuropathic Pain

Keywords

Acute pain; Neuropathic; Pregabalin; Tramadol

Outcome Measures

Primary Outcomes (6)

• Proportion of subjects with a success rate of >50% in pain reduction

  Evaluate the proportion of subjects who reported a success rate of \>50% in pain reduction at completion of the intervention, measure by the VAS (Visual Analog Scale) per treatment group. In a straight 10 centimeter line in which one end means no pain and the other end means the worst pain imaginable, the participants mark the amount of pain feeling at that moment.

  15 days

• Mean change in pain intensity by VAS (Visual Analog Scale)

  Evaluate the mean change in pain intensity reported on days 1, 3, 5, 7, 10, 13, and 15 with respect to its baseline measurement, reported through the VAS (Visual Analog Scale) per treatment group. In a straight 10 centimeter line in which one end means no pain and the other end means the worst pain imaginable, the participants mark the amount of pain feeling at that moment.

  Baseline,1,3,5,7,10, 13 and 15 days

• Mean change in pain intensity by DN4 questionnaire

  Evaluate the mean change in pain intensity reported on days 3, 10 and 15 with respect to its baseline measurement according to the DN4 Questionnaire by treatment group.

  Baseline, 3, 10 and 15 days

• Proportion of subjects requiring dose escalation

  Evaluate the proportion of subjects who required dose escalation (from Pregabalin/Tramadol 75mg/50 to 150 mg/ 50 mg or Pregabalin 75mg to 150 mg, as appropriate) during the intervention, by treatment group.

  Day 3

• Frequency of adverse events

  Compare the frequency of adverse events presented during the study between the treatment groups.

  15 days

• Intensity of adverse events.

  Compare the intensity of adverse events presented by treatment group.

  15 days

Secondary Outcomes (1)

• Adherence percentage

  15 days

Study Arms (2)

Group A: Pregabalin/Tramadol

EXPERIMENTAL

Fixed dose combination tablet of 75 mg Pregabalin and 50 mg of Tramadol, orally, every 12 hours.

Drug: Pregabalin 75mg/ Tramadol 50 mg

Group B: Pregabalin

ACTIVE COMPARATOR

Monotherapy with 75 mg of Pregabalin, orally, every 12 hours.

Drug: Pregabalin 75mg

Interventions

Pregabalin 75mg/ Tramadol 50 mg DRUG

Pharmaceutical Form: Tablet Dosage: 75 mg / 50 mg Administration way: oral

Also known as: LOBUXAL

Group A: Pregabalin/Tramadol

Pregabalin 75mg DRUG

Pharmaceutical Form: Capsule Dosage: 75 mg Administration way: oral

Also known as: Pregabalin

Group B: Pregabalin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any gender.
• That the subject agrees to participate in the study and give its informed consent in writing.
• Age \>18 years and ≤65 years of age at the start of the study.
• Neuropathic Pain Questionnaire (DN4) ≥ 4.
• Patients with proven tolerability (absence of moderate-serious adverse events) to pregabalin, defined by consumption of pregabalin 50 mg/day for 3 days.
• Women of childbearing age who have an acceptable method of contraception (eg barrier, oral hormonal, injectable, subdermal).

You may not qualify if:

• Contraindication and known hypersensitivity to the use of pregabalin and/or tramadol.
• The patient is participating in another clinical study involving an investigational treatment or participated in any in the previous 4 weeks.
• In the medical opinion, a disease that affects the prognosis and prevents outpatient management, for example, but not limited or restricted to: terminal cancer, heart failure, obstruction gastrointestinal including paralytic ileus, suspected surgical abdomen, respiratory failure with scheduled surgical or hospital procedures.
• Positive pregnancy test, women who are pregnant, nursing or planning a pregnancy during the conduct of the study.
• Patients with a diagnosis of respiratory diseases: status asthmaticus, asthma, chronic obstructive pulmonary disease (COPD), cor pulmonale, acute respiratory depression, hypercapnia.
• Patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have received within the last 2 weeks.
• Patients with a history of seizure disorders, epileptic status, and grand mal seizures.
• Patients with a history of severe depression of the central nervous system due to consumption of opiates.
• History of acute intoxications with hypnotics, opioid analgesics and psychotropics.
• History of alcohol or drug abuse (including opiates) in the last year according to DSM-V.
• Patients with a history of severe head trauma and/or brain edema.
• History/presence of any disease or condition which, in the opinion of the Investigator, could pose a risk to the patient or confound the efficacy and safety results of the study.
• Patients with symptoms suggestive of active COVID-19 infection (i.e., fever, cough, dyspnea) and/or contact in the last 14 days with a suspected or positive patient for COVID-19.
• Patients whose participation in the study may be influenced (employment relationship with the center investigator or sponsor, inmates, etc.).

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead

Study Sites (1)

Laboratorio Silanes, S.A. de C.V.

Mexico City, 11000, Mexico

Location

Related Publications (20)

• Taylor RS. Epidemiology of refractory neuropathic pain. Pain Pract. 2006 Mar;6(1):22-6. doi: 10.1111/j.1533-2500.2006.00054.x.

  PMID: 17309705 BACKGROUND

• Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006 Apr;7(4):281-9. doi: 10.1016/j.jpain.2005.11.008.

  PMID: 16618472 BACKGROUND

• Matthiesen T, Wohrmann T, Coogan TP, Uragg H. The experimental toxicology of tramadol: an overview. Toxicol Lett. 1998 Mar 16;95(1):63-71. doi: 10.1016/s0378-4274(98)00023-x.

  PMID: 9650647 BACKGROUND

• Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA, Bockbrader HN. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol. 2003 Mar;43(3):277-83. doi: 10.1177/0091270003251119.

  PMID: 12638396 BACKGROUND

• Ardakani YH, Rouini MR. Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers. Biopharm Drug Dispos. 2007 Dec;28(9):527-34. doi: 10.1002/bdd.584.

  PMID: 17891748 BACKGROUND

• de Moraes NV, Lauretti GR, Lanchote VL. Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers. J Pharm Pharmacol. 2014 Sep;66(9):1222-30. doi: 10.1111/jphp.12255. Epub 2014 Apr 10.

  PMID: 24717054 BACKGROUND

• Bockbrader HN, Radulovic LL, Posvar EL, Strand JC, Alvey CW, Busch JA, Randinitis EJ, Corrigan BW, Haig GM, Boyd RA, Wesche DL. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010 Aug;50(8):941-50. doi: 10.1177/0091270009352087. Epub 2010 Feb 10.

  PMID: 20147618 BACKGROUND

• Chew ML, Plotka A, Alvey CW, Pitman VW, Alebic-Kolbah T, Scavone JM, Bockbrader HN. Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies. Clin Drug Investig. 2014 Sep;34(9):617-26. doi: 10.1007/s40261-014-0211-4.

  PMID: 25078976 BACKGROUND

• Lee S, Kim Y, Lee JJS, Im G, Cho JY, Chung JY, Yoon S. A pharmacokinetic drug-drug interaction study between pregabalin and tramadol in healthy volunteers. Eur J Clin Pharmacol. 2018 Dec;74(12):1605-1613. doi: 10.1007/s00228-018-2543-0. Epub 2018 Aug 22.

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• Vandenbossche J, Richards H, Solanki B, Van Peer A. Single- and multiple-dose pharmacokinetic studies of tramadol immediate-release tablets in children and adolescents. Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):184-92. doi: 10.1002/cpdd.169. Epub 2014 Dec 22.

  PMID: 27140798 BACKGROUND

• Vandenbossche J, Van Peer A, Richards H. Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents. Clin Pharmacol Drug Dev. 2016 Sep;5(5):343-53. doi: 10.1002/cpdd.266. Epub 2016 Jun 12.

  PMID: 27138295 BACKGROUND

• Dou Z, Jiang Z, Zhong J. Efficacy and safety of pregabalin in patients with neuropathic cancer pain undergoing morphine therapy. Asia Pac J Clin Oncol. 2017 Apr;13(2):e57-e64. doi: 10.1111/ajco.12311. Epub 2014 Dec 22.

  PMID: 25530068 BACKGROUND

• Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M. Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998 Jun;50(6):1842-6. doi: 10.1212/wnl.50.6.1842.

  PMID: 9633738 BACKGROUND

• Wang SL, Wang H, Nie HY, Bu G, Shen XD, Wang H. The efficacy of pregabalin for acute pain control in herpetic neuralgia patients: A meta-analysis. Medicine (Baltimore). 2017 Dec;96(51):e9167. doi: 10.1097/MD.0000000000009167.

  PMID: 29390451 BACKGROUND

• Markman J, Resnick M, Greenberg S, Katz N, Yang R, Scavone J, Whalen E, Gregorian G, Parsons B, Knapp L. Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized, double-blind, placebo-controlled phase 3 trial. J Neurol. 2018 Dec;265(12):2815-2824. doi: 10.1007/s00415-018-9063-9. Epub 2018 Sep 21.

  PMID: 30242745 BACKGROUND

• Onakpoya IJ, Thomas ET, Lee JJ, Goldacre B, Heneghan CJ. Benefits and harms of pregabalin in the management of neuropathic pain: a rapid review and meta-analysis of randomised clinical trials. BMJ Open. 2019 Jan 21;9(1):e023600. doi: 10.1136/bmjopen-2018-023600.

  PMID: 30670513 BACKGROUND

• Freynhagen R, Serpell M, Emir B, Whalen E, Parsons B, Clair A, Latymer M. A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain. Pain Pract. 2015 Jan;15(1):47-57. doi: 10.1111/papr.12146. Epub 2013 Nov 27.

  PMID: 24279736 BACKGROUND

• Mercier F, Claret L, Prins K, Bruno R. A Model-Based Meta-analysis to Compare Efficacy and Tolerability of Tramadol and Tapentadol for the Treatment of Chronic Non-Malignant Pain. Pain Ther. 2014 Jun;3(1):31-44. doi: 10.1007/s40122-014-0023-5. Epub 2014 Feb 13.

  PMID: 25135386 BACKGROUND

• Blanco E, Galvez R, Zamorano E, Lopez V, Perez M. [Prevalence of neuropathic pain according to the NP4 test in primary care]. Semergen. 2012 May-Jun;38(4):203-10. doi: 10.1016/j.semerg.2011.10.012. Epub 2011 Dec 21. Spanish.

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• Moon DE, Lee DI, Lee SC, Song SO, Yoon DM, Yoon MH, Kim HK, Lee YW, Kim C, Lee PB. Efficacy and tolerability of pregabalin using a flexible, optimized dose schedule in Korean patients with peripheral neuropathic pain: a 10-week, randomized, double-blind, placebo-controlled, multicenter study. Clin Ther. 2010 Dec;32(14):2370-85. doi: 10.1016/j.clinthera.2011.01.014.

  PMID: 21353106 BACKGROUND

Related Links

• Rincon Carvajal AM, Olaya Osorio CA, Martínez Rojas S, Ibata Bernal L. Recommendations based on in evidence for the management of neuropathic pain in Primary Health Care (Review of the literature). Rev Soc Esp Pain \[Internet\]. 2018 \[cited 2021 Dec 29\];
• Health Secretary. Official Mexican STANDARD NOM-220-SSA1-2016, Installation and operation of the pharmacovigilance

MeSH Terms

Conditions

Neuralgia; Acute Pain

Interventions

Pregabalin; Tramadol

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Rodrigo Suárez Otero, M.D

  Independent consultant

  PRINCIPAL INVESTIGATOR

• Isabel E Rucker, M.D

  Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Luis R Partida, M.D

  Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.

  PRINCIPAL INVESTIGATOR

• Alfonso Hernández Zepeda, M.D

  IMACEN S.A. de C.V.

  PRINCIPAL INVESTIGATOR

• Ma. Dolores Alonso Martínez, M.D

  CICMEX, Centro de Investigación Clínica de México S. de R.L de C.V.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 12, 2022
• Study Start: July 11, 2022
• Primary Completion: April 18, 2023
• Study Completion: April 25, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)