Low Back Pain
Conditions
Brief summary
To evaluate efficacy of Finalgon® cream (1.08% Nicoboxil/ 0.17% Nonivamide) versus placebo in patients with acute low back pain. To investigate the safety and tolerability of repeated use of Finalgon® cream (1.08% Nicoboxil/ 0.17% Nonivamide).
Interventions
DRUGnonivamide + nicoboxil (Finalgon cream)
2 cm cream line for a skin area approximately 20 x 20 cm2 up to 3 times in a 24 hour period
DRUGplacebo matching nonivamide + nicoboxil (Finalgon cream)
2 cm cream line for a skin area of approximately 20 x 20 cm2 up to 3 times in a 24h period
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) guidelines and local regulation prior to participation in the trial. 2. Patients must agree to cooperate with all trial evaluations and perform all required tasks. 3. Patients must have acute nonspecific low back pain, ICD-10 code: M54.5. 4. Patients must have acute low back pain for more than 2 days and less than 21 days (= 3 weeks). 5. Male or female more or equal 18 and less or equal 65 years of age at Visit 1(Baseline). 6. Low back pain Pain intensity more or equal 5 on a 0-10 numerical rating scale (NRS).
Exclusion criteria
1. Patients with a significant disease other than acute nonspecific low back pain. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial. 2. Multilocular pain or panalgesia. 3. History of more than 3 low back pain episodes in the last 6 months. 4. Acute low back pain due to vertebral collapse or neoplastic, inflammatory (ankylosing spondylitis), traumatic, or infective origins. 5. 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. 6. Neurogenic Bladder and/or rectum dysfunction. 7. Any condition, disease or concomitant treatment that in the judgement of the investigator will affect the patient's ability to participate in the clinical trial or which will influence the trial methodology used. 8. 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). 9. Patients with history of treatment of back pain with centrally acting drugs (e.g. opioids) and muscle relaxants within 6 months prior to enrolment. 10. Surgery due to back pain or rehabilitation due to back pain in the last 12 months. 11. Spinal injection back pain treatment within 6 months prior to enrolment. 12. Intake of antidepressant/antipsychotic medication within 4 weeks prior to enrolment. 13. Treatment of the recent low back pain period with oral analgesics for more than 4 consecutive days. 14. Locally applied medication to the back within 24 hours prior to enrolment (topical treatments, injections). 15. Non-pharmacological low back pain treatment (physiotherapy, heat treatment \[e.g. hot water bottle, heat patch\], or massages) within 12 hours prior to enrolment. 16. Administration of other analgesics within 12 h prior to enrolment (exception: acetylsalicylic acid \[ASS\] up to 100 mg/daily for anti-platelet-aggregation therapy). 17. Non-pharmacological low back pain treatment (physiotherapy, heat treatment \[e.g. hot water bottle, heat patch\], or massages) within 12 hours prior to enrolment. 18. Participation in an investigational drug or device trial within 4 weeks prior to enrolment. 19. History of treatment of back pain with centrally acting drugs (e.g. opioids) and muscle relaxants. 20. Treatment of the recent low back pain period with oral analgesics for more than 4 consecutive days. 21. Surgery due to back pain or rehabilitation due to back pain in the last 12 months. 22. Spinal injection back pain treatment within 6 months prior to enrolment. 23. Intake of antidepressant/antipsychotic medication within 4 weeks prior to enrolment. 24. Known hypersensitivity to nicoboxil, nonivamide, or other ingredients of the cream. 25. Known hypersensitivity to paracetamol. 26. Skin lesions (e.g. rash, bruising, laceration) in the back region. 27. Known history of central nervous system diseases with severe intellectual and memory disorders, psychiatric disorders. 28. History of abuse of alcohol/drugs within six months prior to enrolment. 29. Acute and relapsed chronic kidney diseases. 30. Severe hepatocellular insufficiency. 31. Pregnant or nursing women, including female patients with positive ß-HCG test at Visit 1. 32. Female patients of child-bearing potential not using highly effective method of birth control. 33. Patients who are currently participating in another trial or who have been participating in another trial within one month prior to Visit 1, and patients who have previously been randomised in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h) | Baseline and 8 hours after trial medication application | Pain intensity (PI) was assessed on a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain possible) at pre-dose baseline and 0.5, 1, 2, 3, 4, 6 and 8 hours after trial medication application. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. PID8h= Pain intensity (PI)8h - PI(baseline). Means reported are the adjusted means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h) | Baseline and 4 hours after trial medication application | Pain intensity was assessed on a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain possible) at pre-dose baseline and 0.5, 1, 2, 3 and 4 hours after trial medication application. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. PID4h= PI(4h) - PI(baseline). Means reported are the adjusted means. |
| Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day | Baseline and 1 to 4 days | Difference of average pain intensity from pre-dose baseline on the last individual treatment day (The last individual treatment day was the last day on which the patient had recorded the study drug applications within the patient diary). Pain intensity was assessed by the patient using 0-10 numerical rating scale (NRS). Patients were given two 0-10 numerical rating scales (NRS) - to self-report of pain intensity at given time points for the period 0-8 hours post first dose and to self-report of average pain intensity they had at each treatment day. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. APIDtime point = APItime point - PI baseline (time point is the last individual treatment day (either Day 1, 2, 3 or 4 after drug administration)). Means reported are the adjusted means. |
| Patient's Assessment of the Efficacy on the Last Individual Treatment Day | 1 to 4 days | Patients were asked to rate the effect of the study medication for relieving their low back pain using a 4-point verbal rating scale (1=Poor, 2= Fair, 3=Good, 4=Very Good). |
Countries
Russia, Ukraine
Participant flow
Pre-assignment details
Multinational, multi-centre, randomised, double-blind, placebo-controlled, parallel group, 2-arm study with a treatment duration of up to 4 days
Participants by arm
| Arm | Count |
|---|---|
| Placebo Topical administration of Placebo cream. One application consists of 2 cm cream line for a skin area of approximately 20 x 20 square cm (corresponding to approximately 2 x hand size) up to 3 times in a 24 h period. Treatment duration consists of up to 4 days. | 69 |
| Finalgon® Cream (Nicoboxil/ Nonivamide) Topical administration of Finalgon® cream (1.08% Nicoboxil/ 0.17% Nonivamide). One application consists of 2 cm cream line (3.5 mg Nicoboxil/ 0.5 mg Nonivamide) for a skin area of approximately 20 x 20 square cm (corresponding to approximately 2 x hand size) up to 3 times in a 24 h period.
Treatment duration consists of up to 4 days. | 69 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other than the reason specified | 1 | 0 |
| Overall Study | Refused to continue taking medication | 18 | 0 |
Baseline characteristics
| Characteristic | Placebo | Finalgon® Cream (Nicoboxil/ Nonivamide) | Total |
|---|---|---|---|
| Age, Continuous | 42.52 years STANDARD_DEVIATION 11.34 | 44.25 years STANDARD_DEVIATION 12.68 | 43.38 years STANDARD_DEVIATION 12.02 |
| Sex: Female, Male Female | 37 Participants | 49 Participants | 86 Participants |
| Sex: Female, Male Male | 32 Participants | 20 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 69 | 0 / 69 |
| serious Total, serious adverse events | 0 / 69 | 0 / 69 |
Outcome results
Primary
Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h)
Pain intensity (PI) was assessed on a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain possible) at pre-dose baseline and 0.5, 1, 2, 3, 4, 6 and 8 hours after trial medication application. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. PID8h= Pain intensity (PI)8h - PI(baseline). Means reported are the adjusted means.
Time frame: Baseline and 8 hours after trial medication application
Population: Full analysis set (FAS): All patients included in the treated set who provide any post-treatment data for the primary efficacy endpoint constituted the full analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h) | -0.98 points on a scale | Standard Error 0.215 |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h) | -2.82 points on a scale | Standard Error 0.221 |
Comparison: PID8 utilised a restricted maximum likelihood (REML) based repeated measures approach, using all available longitudinal pain intensity observations at each post-baseline time up to 8 hours.~The statistical model was applied to the analysis of change from baseline in pain intensity at 0.5, 1, 2, 3, 4, 6 and 8 hours.p-value: <0.000195% CI: [-2.454, -1.244]REML based repeated measures approach
Secondary
Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day
Difference of average pain intensity from pre-dose baseline on the last individual treatment day (The last individual treatment day was the last day on which the patient had recorded the study drug applications within the patient diary). Pain intensity was assessed by the patient using 0-10 numerical rating scale (NRS). Patients were given two 0-10 numerical rating scales (NRS) - to self-report of pain intensity at given time points for the period 0-8 hours post first dose and to self-report of average pain intensity they had at each treatment day. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. APIDtime point = APItime point - PI baseline (time point is the last individual treatment day (either Day 1, 2, 3 or 4 after drug administration)). Means reported are the adjusted means.
Time frame: Baseline and 1 to 4 days
Population: Full analysis set (FAS): All patients included in the treated set who provide any post-treatment data for the primary efficacy endpoint constituted the full analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day | -2.17 points on a scale | Standard Error 0.272 |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day | -5.13 points on a scale | Standard Error 0.279 |
Comparison: The difference of average pain intensity from pre-dose baseline on the last individual treatment day was analysed using ANCOVA.p-value: <0.000195% CI: [-3.712, -2.205]ANCOVA
Secondary
Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h)
Pain intensity was assessed on a 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain possible) at pre-dose baseline and 0.5, 1, 2, 3 and 4 hours after trial medication application. The left side of each scale (0) is marked 'no pain' and the right side of the scale (10) is marked 'worst pain possible'. PID4h= PI(4h) - PI(baseline). Means reported are the adjusted means.
Time frame: Baseline and 4 hours after trial medication application
Population: Full analysis set (FAS): All patients included in the treated set who provide any post-treatment data for the primary efficacy endpoint constituted the full analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h) | -0.77 points on a scale | Standard Error 0.157 |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h) | -2.11 points on a scale | Standard Error 0.196 |
Comparison: PID4 utilised a restricted maximum likelihood (REML) based repeated measures approach, using all available longitudinal pain intensity observations at each post-baseline time up to 4 hours.~The statistical model was applied to the analysis of change from baseline in pain intensity at 0.5, 1, 2, 3, and 4 hours.p-value: <0.000195% CI: [-1.832, -0.851]REML based repeated measures approach
Secondary
Patient's Assessment of the Efficacy on the Last Individual Treatment Day
Patients were asked to rate the effect of the study medication for relieving their low back pain using a 4-point verbal rating scale (1=Poor, 2= Fair, 3=Good, 4=Very Good).
Time frame: 1 to 4 days
Population: Full analysis set (FAS): All patients included in the treated set who provide any post-treatment data for the primary efficacy endpoint constituted the full analysis set.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Placebo | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Very good | 13.0 percentage of participants | 0.272 |
| Placebo | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Good | 17.4 percentage of participants | — |
| Placebo | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Poor | 47.8 percentage of participants | — |
| Placebo | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Missing | 1.4 percentage of participants | — |
| Placebo | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Fair | 20.3 percentage of participants | — |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Fair | 13.0 percentage of participants | — |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Very good | 29.0 percentage of participants | 0.279 |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Missing | 0.0 percentage of participants | — |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Good | 58.0 percentage of participants | — |
| Finalgon® Cream (Nicoboxil/ Nonivamide) | Patient's Assessment of the Efficacy on the Last Individual Treatment Day | Poor | 0.0 percentage of participants | — |
Comparison: For the analysis of the repeated multinomial efficacy endpoint 'patient assessment of efficacy' on the last individual treatment day, ordinal logistic regression models is used.~Only non-missing data is analysed in the statistical model.p-value: <0.000195% CI: [5.342, 24.199]Regression, Logistic