Acute Pain
Conditions
Brief summary
This randomised, controlled multi-centre parallel group trial will assess the efficacy and tolerability of a topical formulation gel of the combination of diclofenac and capsaicin in comparison to gels with diclofenac alone, capsaicin alone, and placebo for the treatment of acute back pain or neck pain
Interventions
DRUGDiclofenac
DRUGCapsaicin
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent at Visit 1 in accordance with Good Clinical Practice and local legislation * Male or female patients \>=18 years with current diagnosis of acute back pain or of neck pain for at least 24 hours, but less than 21 days * Acute back pain or acute neck pain resulting in pain on movement (POM) \>= 50 mm (Visual Analogue Scale 0-100) for at least one POM procedure out of 5 standardized procedures. * Sensitivity to algometric pressure on the painful trigger point \<= 25 N/cm2 * Women of childbearing potential must be ready and able to use highly effective methods of birth control
Exclusion criteria
* History of 3 or more episodes of back or neck pain in the last 6 months excluding the current episode * Surgery due to back or neck pain or rehabilitation due to back or neck pain in the last 12 months * Back or neck pain that is attributable to any specific identifiable cause (e.g. disc prolapse, spondylolisthesis, osteomalacia, inflammatory arthritis, metabolic, neurological diseases or tumour) * Trauma or strains of the back or neck muscles within the last 3 months * Prior use within the last 3 days before Visit 1 or concomitant use of any anti-inflammatory drugs, heparinoids, muscle relaxants or analgesics. Long-acting glucocorticoids must have been discontinued 10 days before study entry. Spinal injections should have been discontinued in due time (investigator's judgement) before patient enrolment to allow complete wash-out of the active ingredient based on investigator's judgment * Non-pharmacological treatment (physiotherapy, heat treatment (e.g. heat patch, hot water bottle), or massage, acupuncture, transcutaneous electrical nerve stimulation) or locally applied pharmacological product to the back or neck area 24 hours prior study entry and during the study period * Known severe hepatocellular insufficiency, severe renal insufficiency or Gilbert's syndrome (Morbus Meulengracht) * Any other medical condition that would interfere with efficacy and safety assessments based on investigator's judgement or any on-going clinical condition that would jeopardize patient's or site personnel's safety or study compliance based on investigator judgement. * Known intolerance or hypersensitivity to the active ingredients or any excipient(s). * Patients in whom attacks of asthma, bronchospasm, rhinitis or urticaria were precipitated by the intake of Acetyl salicylic acid (ASS) or other NSAIDs * Irritated skin (based on investigator's judgement), skin wounds, eczema or open injuries at application site * Negative experience in the past with heat treatments for muscle complaints * Patient not able to understand and comply with trial requirements based on investigators judgement * Alcohol or drug abuse * Participation in a clinical trial within the previous 30 days or simultaneous participation in another clinical trial * Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application | Baseline and Day 2 | Pain on movement (POM) was used to assess pain measurement for back and neck pain. The standardized movements have been established for which the measurement was taken. POMwp was the POM measure that gave the highest score at baseline; i.e. POM of worst procedure. Pain intensity was assessed at rest after standing in an upright position relatively motionless for 1 minute. The pain was evaluated by asking patient 'How would you rate your pain right now?' and by using a visual analogue scale (VAS) ranging from 0-10 centimeters (cm) wherein 0 cm = no pain to 10 cm = worst pain possible. The results presented here are adjusted mean change from baseline and standard error for POMwp in cm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h)) | 0 to 120 hours after start of treatment | This is a key secondary endpoint. AUC for POMwp calculated from 0 to 120 h that is for first five treatment days using the trapezoidal rule divided by the observation time. The results presented here are adjusted mean and standard error for POMwp AUC (0-120 h) in centimeters (cm). The AUC represents POMwp as an average over the first 5 treatment days (Day 1 until Day 6 morning) - it is not meant here as a PK parameter (concentration over time). |
| Number of Patients With Decrease in POMwp of at Least 30% From Baseline | Baseline and day 2 | This outcome measures the pattern of number of patients with a decrease in POMwp of at least 30% from baseline at 1 hour after dosing on Day 2 evening. |
| Number of Patients With Decrease in POMwp of at Least 50% From Baseline | Baseline and day 2 | This outcome measures the pattern of number of patients with a decrease in POMwp of at least 50% from baseline at 1 hour after dosing on Day 2 evening. |
| POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h)) | 0 to 72 hours after start of treatment | This is a key secondary endpoint. AUC for POMwp calculated from 0 to 72 h that is for first three treatment days using the trapezoidal rule divided by the observation time. The results presented here are adjusted mean and standard error for POMwp AUC (0-72 h) in centimeters (cm). The AUC represents POMwp as an average over the first 3 treatment days (Day 1 until Day 4 morning) - it is not meant here as a pharmacokinetics (PK) parameter (concentration over time). |
| Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application | Baseline and Day 2 | PA is a method described to determine pressure pain threshold (PPT) by applying controlled pressure to a given body point. The results presented here are adjusted mean change from baseline and standard error for PA. |
| Change From Baseline in Pressure Algometry (PA) at Day 6 Morning | Baseline and Day 6 | PA is a method described to determine pressure pain threshold (PPT) by applying controlled pressure to a given body point. The results presented here are adjusted mean change from baseline and standard error for PA. |
| Change From Baseline in POMwp (cm) at Day 6 Morning | Baseline and Day 6 | Pain on movement (POM) was used to assess pain measurement for back and neck pain. The standardized movements have been established for which the measurement was taken. POMwp was the POM measure that gave the highest score at baseline; i.e. POM of worst procedure. Pain intensity was assessed at rest after standing in an upright position relatively motionless for 1 minute. The pain was evaluated by asking patient 'How would you rate your pain right now?' and by using a visual analogue scale (VAS) ranging from 0-10 cm wherein 0 cm = no pain to 10 cm = worst pain possible. The results presented here are adjusted mean change from baseline and standard error for POMwp in centimeters (cm). |
Countries
Germany, Russia
Participant flow
Recruitment details
This was a randomised, placebo and active treatment-controlled, double-blind, parallel group study. Out of 757 enrolled patients with acute back or neck pain, 746 were randomised and treated with 4 topical treatments administered twice daily for 4 to 7 days.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be entered to trial if any of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Gel Patients were topically applied matching Placebo 2 gram (g) gel, twice daily with 12 ± 4 hours (h) between applications. | 75 |
| Capsaicin (0.075%) Gel Patients were topically applied Capsaicin 2 g gel (1.5 milligram (mg) Capsaicin), twice daily with 12 ± 4 hours (h) between applications. | 223 |
| Diclofenac (2%) Gel Patients were topically applied Diclofenac 2 g gel (40 milligram (mg) Diclofenac), twice daily with 12 ± 4 hours (h) between applications. | 223 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel Patients were topically applied Diclofenac + Capsaicin 2 g gel (40 mg diclofenac, 1.5 mg capsaicin), twice daily with 12 ± 4 hours (h) between applications. | 225 |
| Total | 746 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 6 | 2 | 3 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Overall Study | Refusal to continue medication | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Capsaicin (0.075%) Gel | Total | Diclofenac (2%) +Capsaicin (0.075%) Gel | Placebo Gel | Diclofenac (2%) Gel |
|---|---|---|---|---|---|
| Age, Continuous | 43.2 Years STANDARD_DEVIATION 15.42 | 43.9 Years STANDARD_DEVIATION 15.52 | 44.2 Years STANDARD_DEVIATION 15.49 | 45.3 Years STANDARD_DEVIATION 14.78 | 44.0 Years STANDARD_DEVIATION 15.96 |
| Application site Back | 97 Participants | 316 Participants | 95 Participants | 30 Participants | 94 Participants |
| Application site Neck | 126 Participants | 430 Participants | 130 Participants | 45 Participants | 129 Participants |
| Country Germany | 205 Participants | 684 Participants | 205 Participants | 69 Participants | 205 Participants |
| Country Russia | 18 Participants | 62 Participants | 20 Participants | 6 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 9 Participants | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 220 Participants | 737 Participants | 222 Participants | 75 Participants | 220 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain on movement of worst procedure (POMwp) | 7.22 Units on scale STANDARD_DEVIATION 1.157 | 7.26 Units on scale STANDARD_DEVIATION 1.198 | 7.28 Units on scale STANDARD_DEVIATION 1.148 | 7.20 Units on scale STANDARD_DEVIATION 1.246 | 7.29 Units on scale STANDARD_DEVIATION 1.274 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 9 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 216 Participants | 723 Participants | 216 Participants | 73 Participants | 218 Participants |
| Sex: Female, Male Female | 128 Participants | 444 Participants | 136 Participants | 44 Participants | 136 Participants |
| Sex: Female, Male Male | 95 Participants | 302 Participants | 89 Participants | 31 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 223 | 0 / 223 | 0 / 225 |
| other Total, other adverse events | 4 / 75 | 29 / 223 | 7 / 223 | 26 / 225 |
| serious Total, serious adverse events | 0 / 75 | 0 / 223 | 0 / 223 | 0 / 225 |
Outcome results
Primary
Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application
Pain on movement (POM) was used to assess pain measurement for back and neck pain. The standardized movements have been established for which the measurement was taken. POMwp was the POM measure that gave the highest score at baseline; i.e. POM of worst procedure. Pain intensity was assessed at rest after standing in an upright position relatively motionless for 1 minute. The pain was evaluated by asking patient 'How would you rate your pain right now?' and by using a visual analogue scale (VAS) ranging from 0-10 centimeters (cm) wherein 0 cm = no pain to 10 cm = worst pain possible. The results presented here are adjusted mean change from baseline and standard error for POMwp in cm.
Time frame: Baseline and Day 2
Population: Full analysis set (FAS): All patients in treated set with a baseline value pre application for POMwp at Visit 1 and at least 1 POMwp value during assessment times at Visit 1 (Day 1 morning 1h after application), Visit 2 (Day 2, morning 1h after application), Visit 3 (Day 2 evening before application) or Visit 3 (Day 2 evening 1h after application)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application | -2.45 Units on a scale | Standard Error 0.252 |
| Capsaicin (0.075%) Gel | Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application | -3.26 Units on a scale | Standard Error 0.16 |
| Diclofenac (2%) Gel | Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application | -2.33 Units on a scale | Standard Error 0.16 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Change in POM Between Baseline and Day 2 Evening, 1 Hour After Drug Application | -3.05 Units on a scale | Standard Error 0.159 |
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between placebo and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: 0.030395% CI: [-1.15, -0.06]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between capsaicin and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: 0.288695% CI: [-0.18, 0.6]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between diclofenac and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: 0.000395% CI: [-1.1, -0.33]Mixed Models Analysis
Secondary
Change From Baseline in POMwp (cm) at Day 6 Morning
Pain on movement (POM) was used to assess pain measurement for back and neck pain. The standardized movements have been established for which the measurement was taken. POMwp was the POM measure that gave the highest score at baseline; i.e. POM of worst procedure. Pain intensity was assessed at rest after standing in an upright position relatively motionless for 1 minute. The pain was evaluated by asking patient 'How would you rate your pain right now?' and by using a visual analogue scale (VAS) ranging from 0-10 cm wherein 0 cm = no pain to 10 cm = worst pain possible. The results presented here are adjusted mean change from baseline and standard error for POMwp in centimeters (cm).
Time frame: Baseline and Day 6
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | Change From Baseline in POMwp (cm) at Day 6 Morning | -3.83 Units on a scale | Standard Error 0.282 |
| Capsaicin (0.075%) Gel | Change From Baseline in POMwp (cm) at Day 6 Morning | -5.08 Units on a scale | Standard Error 0.175 |
| Diclofenac (2%) Gel | Change From Baseline in POMwp (cm) at Day 6 Morning | -3.77 Units on a scale | Standard Error 0.175 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Change From Baseline in POMwp (cm) at Day 6 Morning | -4.88 Units on a scale | Standard Error 0.174 |
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between placebo and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: 0.000895% CI: [-1.67, -0.44]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between capsaicin and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: 0.372695% CI: [-0.24, 0.64]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in POMwp from baseline between diclofenac and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline POMwp and baseline POMwp by time interaction.p-value: <0.000195% CI: [-1.56, -0.68]Mixed Models Analysis
Secondary
Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application
PA is a method described to determine pressure pain threshold (PPT) by applying controlled pressure to a given body point. The results presented here are adjusted mean change from baseline and standard error for PA.
Time frame: Baseline and Day 2
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application | 3.89 Newton/centimeter square (N/cm^2) | Standard Error 0.795 |
| Capsaicin (0.075%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application | 3.46 Newton/centimeter square (N/cm^2) | Standard Error 0.526 |
| Diclofenac (2%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application | 3.00 Newton/centimeter square (N/cm^2) | Standard Error 0.53 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 2 Evening, Before Drug Application | 3.77 Newton/centimeter square (N/cm^2) | Standard Error 0.526 |
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between placebo and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.88195% CI: [-1.78, 1.53]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between capsaicin and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.609495% CI: [-0.87, 1.49]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between diclofenac and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.204795% CI: [-0.42, 1.95]Mixed Models Analysis
Secondary
Change From Baseline in Pressure Algometry (PA) at Day 6 Morning
PA is a method described to determine pressure pain threshold (PPT) by applying controlled pressure to a given body point. The results presented here are adjusted mean change from baseline and standard error for PA.
Time frame: Baseline and Day 6
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | Change From Baseline in Pressure Algometry (PA) at Day 6 Morning | 8.01 Newton/centimeter square (N/cm^2) | Standard Error 1.199 |
| Capsaicin (0.075%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 6 Morning | 9.38 Newton/centimeter square (N/cm^2) | Standard Error 0.737 |
| Diclofenac (2%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 6 Morning | 7.64 Newton/centimeter square (N/cm^2) | Standard Error 0.74 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Change From Baseline in Pressure Algometry (PA) at Day 6 Morning | 9.66 Newton/centimeter square (N/cm^2) | Standard Error 0.737 |
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between placebo and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.219395% CI: [-0.98, 4.27]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between capsaicin and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.767295% CI: [-1.58, 2.15]Mixed Models Analysis
Comparison: A Mixed Model Repeat Measures (MMRM) analysis was used to compare change in PA from baseline between diclofenac and combination therapy diclofenac + capsaicin. MMRM model included fixed effects of treatment, country, application site (back/neck), time and fixed covariates of baseline PA and baseline PA by time interaction.p-value: 0.033995% CI: [0.15, 3.88]Mixed Models Analysis
Secondary
Number of Patients With Decrease in POMwp of at Least 30% From Baseline
This outcome measures the pattern of number of patients with a decrease in POMwp of at least 30% from baseline at 1 hour after dosing on Day 2 evening.
Time frame: Baseline and day 2
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Gel | Number of Patients With Decrease in POMwp of at Least 30% From Baseline | 34 Participants |
| Capsaicin (0.075%) Gel | Number of Patients With Decrease in POMwp of at Least 30% From Baseline | 150 Participants |
| Diclofenac (2%) Gel | Number of Patients With Decrease in POMwp of at Least 30% From Baseline | 107 Participants |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Number of Patients With Decrease in POMwp of at Least 30% From Baseline | 134 Participants |
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 30% from baseline between placebo and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.020295% CI: [1.1, 3.21]Regression, Logistic
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 30% from baseline between capsaicin and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.120695% CI: [0.49, 1.09]Regression, Logistic
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 30% from baseline between diclofenac and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.012295% CI: [1.11, 2.39]Regression, Logistic
Secondary
Number of Patients With Decrease in POMwp of at Least 50% From Baseline
This outcome measures the pattern of number of patients with a decrease in POMwp of at least 50% from baseline at 1 hour after dosing on Day 2 evening.
Time frame: Baseline and day 2
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Gel | Number of Patients With Decrease in POMwp of at Least 50% From Baseline | 20 Participants |
| Capsaicin (0.075%) Gel | Number of Patients With Decrease in POMwp of at Least 50% From Baseline | 95 Participants |
| Diclofenac (2%) Gel | Number of Patients With Decrease in POMwp of at Least 50% From Baseline | 50 Participants |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | Number of Patients With Decrease in POMwp of at Least 50% From Baseline | 85 Participants |
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 50% from baseline between placebo and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.064395% CI: [0.97, 3.09]Regression, Logistic
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 50% from baseline between capsaicin and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.347995% CI: [0.57, 1.22]Regression, Logistic
Comparison: A logistic regression was used to compare change in number of patients with a decrease in POMwp of at least 50% from baseline between diclofenac and combination therapy diclofenac + capsaicin. The likelihood-ratio test was used to test for differences between treatments.p-value: 0.000495% CI: [1.4, 3.22]Regression, Logistic
Secondary
POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h))
This is a key secondary endpoint. AUC for POMwp calculated from 0 to 120 h that is for first five treatment days using the trapezoidal rule divided by the observation time. The results presented here are adjusted mean and standard error for POMwp AUC (0-120 h) in centimeters (cm). The AUC represents POMwp as an average over the first 5 treatment days (Day 1 until Day 6 morning) - it is not meant here as a PK parameter (concentration over time).
Time frame: 0 to 120 hours after start of treatment
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h)) | 3.92 cm | Standard Error 0.23 |
| Capsaicin (0.075%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h)) | 3.10 cm | Standard Error 0.156 |
| Diclofenac (2%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h)) | 4.10 cm | Standard Error 0.156 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 120 Hours (h) (POMwp AUC(0-120 h)) | 3.41 cm | Standard Error 0.154 |
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-120 h) between placebo and combination therapy diclofenac + capsaicinp-value: 0.034795% CI: [-0.97, -0.04]ANCOVA
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-120 h) between capsaicin and combination therapy diclofenac + capsaicinp-value: 0.062295% CI: [-0.02, 0.65]ANCOVA
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-120 h) between diclofenac and combination therapy diclofenac + capsaicinp-value: <0.000195% CI: [-1.01, -0.35]ANCOVA
Secondary
POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h))
This is a key secondary endpoint. AUC for POMwp calculated from 0 to 72 h that is for first three treatment days using the trapezoidal rule divided by the observation time. The results presented here are adjusted mean and standard error for POMwp AUC (0-72 h) in centimeters (cm). The AUC represents POMwp as an average over the first 3 treatment days (Day 1 until Day 4 morning) - it is not meant here as a pharmacokinetics (PK) parameter (concentration over time).
Time frame: 0 to 72 hours after start of treatment
Population: Treated set (TS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h)) | 4.62 cm | Standard Error 0.213 |
| Capsaicin (0.075%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h)) | 3.95 cm | Standard Error 0.145 |
| Diclofenac (2%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h)) | 4.81 cm | Standard Error 0.145 |
| Diclofenac (2%) +Capsaicin (0.075%) Gel | POMwp Area Under the Curve (AUC) Calculated From 0 to 72 Hours (h) (POMwp AUC(0-72 h)) | 4.25 cm | Standard Error 0.143 |
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-72 h) between placebo and combination therapy diclofenac + capsaicinp-value: 0.095695% CI: [-0.8, 0.07]ANCOVA
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-72 h) between capsaicin and combination therapy diclofenac + capsaicinp-value: 0.056495% CI: [-0.01, 0.61]ANCOVA
Comparison: An analysis of covariance (ANCOVA) was used to compare POMwp AUC(0-72 h) between diclofenac and combination therapy diclofenac + capsaicinp-value: 0.000495% CI: [-0.87, -0.25]ANCOVA