Clinical trial NCT01708915: Nonivamide/Nicoboxil Ointment in Acute Low Back Pain
Official title: A Multi-centre, Double-blind, Randomised, Parallel Group Study to Assess the Efficacy and Safety of Multiple Doses of Topically Applied Hyperemisation-inducing Ointment (2cm Ointment Line Per Application; up to 3 Times Daily for up to 4 Days) Containing 2.5% Nicoboxil/0.4% Nonivamide Versus 2.5% Nicoboxil, 0.4% Nonivamide and Placebo in Patients 18 to 65 Years of Age With Acute Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Low Back Pain
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-10-17
Enrollment: 805
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the efficacy and tolerability of Nicoboxil/Nonivamide ointment in comparison to Nicoboxil, Nonivamide, and placebo ointments for the treatment of acute low back pain.


Eligibility criteria: Inclusion criteria:

* Patients must sign and date an Informed Consent consistent with International Conference on Hermonisation (ICH)/Good Clinical Practice (GCP) guidelines and local regulation prior to participation in the trial.
* Patients must agree to cooperate with all trial evaluations and perform all required tasks.
* Acute low back pain for more than 2 days and less than 21 days (= 3 weeks)
* Male or female patients aged 18 to 65 years
* Low back pain rating \>5 on a 0-10 numerical rating scale (NRS).
* Female patients of childbearing potential may participate only in case of availability of a negative urine pregnancy test and a confirmed menstrual period prior to study entry and using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, appropriate intrauterine devices, sexual abstinence or vasectomised partner. Barrier methods of contraception (e.g. condom, diaphragma or occlusive cap) are accepted if used in combination with spermicides (e.g. foam, gel). Female patients will be considered being of childbearing potential unless surgically sterilised by bilateral tubal ligation/salpingectomy or hysterectomy or post-menopausal for at least one year.

Exclusion criteria:

* Multilocular pain or panalgesia
* History of more than three low back pain episodes in the last six months
* Abnormal findings in at least one of the following assessments: Achilles tendon reflex, patella reflex, heel walking, toe walking, cutaneous sensitivity of the legs (including gluteal region), paresis tests in supine position upon dorsiflexion, plantarflexion, hip flexion, knee extension
* Bladder and/or rectum dysfunction
* Acute low back pain due to vertebral collapse or neoplastic, inflammatory (ankylosing spondylitis), traumatic, or infective origins
* Any condition, disease or concomitant treatment that in the judgement of the Investigator will affect the subject's ability to participate in the clinical trial or which will influence the test methodology used
* Negative experience in the past with heat treatment for muscle complaints (e. g. hot water bottle, heat pads, hyperemisation-inducing topical creams, ointments or patches)
* History of treatment of back pain with centrally acting analgesics (e. g. opioids) and muscle relaxants
* Surgery due to back pain or rehabilitation due to back pain in the last 12 months
* Spinal injection back pain treatment within 6 months prior to enrollment
* Intake of antidepressant/antipsychotic medication within 4 weeks prior to enrollment
* Treatment of the recent low back pain period with oral analgesics for more than 4 consecutive days
* Locally applied medication to the back within 48 hours prior to enrollment (topical treatments, injections)
* Administration of other analgesics within 24 h prior to enrollment (exception: acetyl salicylic acid (ASS) up to 100 mg/daily for anti platelet-aggregation therapy)
* Non-pharmacological low back pain treatment (physiotherapy, heat treatment (e.g. hot water bottle, heat patch, or massages) within 12 h prior to enrollment
* Participation in an investigational drug or device trial within 4 weeks prior to enrollment
* Hypersensitivity to Nicoboxil, Nonivamide, or paracetamol
* Known hypersensitivity to any other ingredient, especially to sorbic acid/sorbate, to citronella oil containing e.g. the fragrance compounds geraniol, citronellol and citronellal, or to relevant flowers containing these compounds such as geranium, lavender, jasmine or rose. For patients with known hypersensitivity to perfumes or known type IV hypersensitivity to fragrance-mix I, the application of the investigational product should be performed only with particular caution.
* Skin lesions (e. g., rash, dermatitis, bruising, laceration) in the back region
* Drug dependence and/or alcohol abuse
* Severe hepatocellular insufficiency
* Patients who are pregnant or breast-feeding

Primary outcomes:
measure: Pain Intensity Difference (PID) Between Pre-dose Baseline and 8hours After First Application
timeFrame: Baseline and 8 hours after first ointment application
Secondary outcomes:
measure: Pain Intensity Difference (PID) Between Pre-dose Baseline and 4 Hours After First Application
timeFrame: Baseline and 4 hours after first ointment application
measure: Difference Between Baseline Pain Intensity and Average Pain Intensity on the Last Individual Treatment Day
timeFrame: Baseline and 1 to 4 days
measure: Patient Assessment of Efficacy on the Last Individual Treatment Day
timeFrame: 1 to 4 days
Other outcomes:
Locations:
city: Bad Lippspringe
country: Germany
facility: 69.52.49007 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49003 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49026 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49032 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49033 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 69.52.49041 Boehringer Ingelheim Investigational Site
city: Einbeck
country: Germany
facility: 69.52.49002 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 69.52.49024 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 69.52.49031 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 69.52.49036 Boehringer Ingelheim Investigational Site
city: Everswinkel
country: Germany
facility: 69.52.49005 Boehringer Ingelheim Investigational Site
city: Fürth
country: Germany
facility: 69.52.49039 Boehringer Ingelheim Investigational Site
city: Goch
country: Germany
facility: 69.52.49018 Boehringer Ingelheim Investigational Site
city: Großheirath-Rossach
country: Germany
facility: 69.52.49025 Boehringer Ingelheim Investigational Site
city: Haag
country: Germany
facility: 69.52.49022 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 69.52.49009 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 69.52.49019 Boehringer Ingelheim Investigational Site
city: Kaarst
country: Germany
facility: 69.52.49015 Boehringer Ingelheim Investigational Site
city: Karlsruhe-Rüppurr
country: Germany
facility: 69.52.49042 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 69.52.49027 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 69.52.49035 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 69.52.49040 Boehringer Ingelheim Investigational Site
city: Köthen
country: Germany
facility: 69.52.49013 Boehringer Ingelheim Investigational Site
city: Künzing
country: Germany
facility: 69.52.49014 Boehringer Ingelheim Investigational Site
city: Ludwigshafen
country: Germany
facility: 69.52.49034 Boehringer Ingelheim Investigational Site
city: Meßkirch
country: Germany
facility: 69.52.49028 Boehringer Ingelheim Investigational Site
city: Meßkirch
country: Germany
facility: 69.52.49030 Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: 69.52.49029 Boehringer Ingelheim Investigational Site
city: Neunkirchen
country: Germany
facility: 69.52.49012 Boehringer Ingelheim Investigational Site
city: Rodgau
country: Germany
facility: 69.52.49020 Boehringer Ingelheim Investigational Site
city: Siegen
country: Germany
facility: 69.52.49037 Boehringer Ingelheim Investigational Site
city: Stockach
country: Germany
facility: 69.52.49016 Boehringer Ingelheim Investigational Site
city: Straßkirchen
country: Germany
facility: 69.52.49010 Boehringer Ingelheim Investigational Site
city: Villingen-Schwenningen
country: Germany
facility: 69.52.49021 Boehringer Ingelheim Investigational Site
city: Wangen
country: Germany
facility: 69.52.49023 Boehringer Ingelheim Investigational Site
city: Weilburg
country: Germany
facility: 69.52.49011 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Gaubitz M, Schiffer T, Holm C, Richter E, Pisternick-Ruf W, Weiser T. Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back - A randomized, controlled trial. Eur J Pain. 2016 Feb;20(2):263-73. doi: 10.1002/ejp.719. Epub 2015 Apr 30.