Healthy
Conditions
Brief summary
The main objective of this study is to assess the relative systemic bioavailability of diclofenac in the presence and absence of capsaicin by comparing the systemic bioavailability of diclofenac from a combination product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) with two diclofenac only products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel, following topical administration. In order to examine potential racial differences in pharmacokinetics (PK), the study population will be stratified 50:50, Caucasian versus Black people. With respect to the main objective, additionally a supportive analysis will be performed to investigate the influence of race on the intra-individual bioavailability ratios.
Interventions
DRUGDiclofenac Sodium
twice daily
DRUGDiclofenac & Capsaicin
twice daily
twice daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Healthy males and females, 18 to 50 years (inclusive) at time of screening. * Body mass index (BMI) between 18.5 and 29.9 kg/m2 (inclusive). * Body mass not less than 50 kg for males and females. * Findings for medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be normal or within laboratory reference ranges for the relevant laboratory tests, unless the PI considers the deviation to be not clinically significant for the purpose of the study. * Non-smokers. * Females, if: * Not of childbearing potential, * Of childbearing potential, the following conditions are to be met: * Negative pregnancy test. * Not lactating. * Abstaining from sexual activity (if this is the usual lifestyle of the subject) or must agree to use an accepted method of contraception, and agree to continue with the same method throughout the study. * Written informed consent given for participation in the study. * Further inclusion criteria apply.
Exclusion criteria
* Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements. * Current alcohol use \> 21 units of alcohol per week for males and \> 14 units of alcohol per week for females. One unit (10 g alcohol) is equal to beer (330 mL), wine (200 mL), or distilled spirits (25 mL) per day. * Regular exposure to substances of abuse (other than alcohol) within the past year. * Use of any medication, prescribed or over-the-counter (especially products containing diclofenac or use of other oral nonsteroidal anti-inflammatory drugs \[NSAIDS\]) or herbal remedies, within 2 weeks before the first administration of Investigational medicinal product (IMP) except if this will not affect the outcome of the study in the opinion of the PI (Principal Investigator) (in collaboration with the Sponsor). In this study the concomitant use of hormonal contraceptives is allowed. * Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for anti-bodies or insulin), whichever is the longer before administration of IMP in this study, at the discretion of the PI. * Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system. * A major illness during the 3 months before commencement of the screening period. * History of hypersensitivity or allergy (acute rhinitis, angioedema, urticaria or bronchial asthma) to the IMP or its excipients or any related medication (Aspirin or any other NSAID). * History of hypersensitivity or allergy to cayenne pepper or other capsaicinoids (paprika plants). * History of bronchospasm or bronchial asthma, arterial hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease. * History or current diagnosis of gastrointestinal bleeding or peptic ulcer disease. * Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome. * Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP (Investigational medicinal product) . * Bruises, damaged skin, eczema or wounds on the application site, or the application site inappropriate for applying the IMP in the opinion of the PI (Principal Investigator). * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration | AUC0-τ,ss, Area under the plasma concentration-time curve (AUC) over one dosing interval at steady state for diclofenac at day 7 (τ = 12 hours). Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and Geometric Means (gMeans) per treatment and race are very similar, only gMeans per treatment and race are presented. |
| Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration | Cmax,ss, Maximum plasma of diclofenac concentration during a dosage interval obtained directly from the concentration-time data at steady state for diclofenac on day 7. Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and gMeans per treatment and race are very similar, only gMeans per treatment and race are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration | tmax,ss, Time to maximum observed plasma concentration at steady state for diclofenac at day 7 (tmax,ss). Descriptive statistics by race are reported in addition. |
| Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration | Average plasma concentration (Cav,ss) calculated as AUC0-t,ss divided by τ=12 hours (τ is the duration of the dosing interval). Descriptive statistics by race are reported in addition. |
| Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration | Percentage peak-trough fluctuation (%PTF) which was calculated as \[100\*(Cmax,ss - Cpre,ss)/Cav,ss\] for Diclofenac. Descriptive statistics by race are reported in addition. |
Countries
South Africa
Participant flow
Recruitment details
This was an open-label, randomized, 3-treatment periods (each of which included a multiple-dose period of 7 days \[twice daily and only in the morning on Day 7\] and two pharmacokinetic profile periods of 12 hours \[Day 1\] and 24 hours \[Day 7\]) separated by a wash out period of at least 7 days.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended the trial site and it was ensured that they met all strictly implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| A-B-R Test A: Diclofenac Mono Gel 2% (B151002900/EI4659); Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699); Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A)
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel in period 1, followed by period 2 with 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel and in period 3 with 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| B-R-A Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699); Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A); Test A: Diclofenac Mono Gel 2% (B151002900/EI4659)
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel in period 1, followed by period 2 with 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel and in period 3 with 2 grams of Diclofenac 2% immediate release topical mono gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| R-A-B Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A); Test A: Diclofenac Mono Gel 2% (B151002900/EI4659); Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699)
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel in period 1, followed by period 2 with 2 grams of Diclofenac 2% immediate release topical mono gel and in period 3 with 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| R-B-A Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A); Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699); Test A: Diclofenac Mono Gel 2% (B151002900/EI4659)
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel in period 1, followed by period 2 with 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel and in period 3 with 2 grams of Diclofenac 2% immediate release topical mono gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| A-R-B Test A: Diclofenac Mono Gel 2% (B151002900/EI4659); Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A); Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699)
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel in period 1, followed by period 2 with 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel and in period 3 with 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| B-A-R Test B: Combination of Diclofenac 2% + Capsaicin 0.075% Topical Gel (B151002897/EI4699); Test A: Diclofenac Mono Gel 2% (B151002900/EI4659); Reference: Voltarol® Emulgel 2.32% (B161000473/parental batch R03717A)
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel in period 1, followed by period 2 with 2 grams of Diclofenac 2% immediate release topical mono gel and in period 3 with 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel, each treatment twice daily for multiple dose period of 6 days and only once in the morning on Day 7.
All treatment periods were separated by a wash-out period of at least 7 days. | 8 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 Including Washout 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 Including Washout 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 |
| Period 3 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | B-R-A | R-A-B | R-B-A | A-R-B | B-A-R | Total | A-B-R |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 29.4 Years STANDARD_DEVIATION 10.04 | 27.6 Years STANDARD_DEVIATION 7.84 | 28.5 Years STANDARD_DEVIATION 8.82 | 22.5 Years STANDARD_DEVIATION 3.38 | 26.0 Years STANDARD_DEVIATION 8.16 | 27.5 Years STANDARD_DEVIATION 8.24 | 30.9 Years STANDARD_DEVIATION 9.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 24 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 24 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 14 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 5 Participants | 7 Participants | 5 Participants | 34 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 | 0 / 47 |
| other Total, other adverse events | 9 / 47 | 44 / 46 | 3 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 46 | 0 / 47 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7)
AUC0-τ,ss, Area under the plasma concentration-time curve (AUC) over one dosing interval at steady state for diclofenac at day 7 (τ = 12 hours). Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and Geometric Means (gMeans) per treatment and race are very similar, only gMeans per treatment and race are presented.
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Population: Pharmacokinetic Population (PK): This population consists of all subjects in the safety population for whom at least one of area under the plasma concentration-time curve over one dosing interval or maximum steady-state plasma drug concentration during a dosage interval could be calculated for one treatment and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac 2% (A) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Caucasian | 35.182 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 57.46 |
| Diclofenac 2% (A) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | Overall | 46.855 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 66.01 |
| Diclofenac 2% (A) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Black | 60.930 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 58.76 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Caucasian | 29.704 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 51.32 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Black | 53.628 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 47.37 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | Overall | 40.175 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 59.38 |
| Voltarol® 2.32% Gel (R) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Caucasian | 67.513 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 73.15 |
| Voltarol® 2.32% Gel (R) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | By race: Black | 105.670 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 42.13 |
| Voltarol® 2.32% Gel (R) | Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) | Overall | 83.644 Hour*nanogram/millilitre (h*ng/mL) | Geometric Coefficient of Variation 64.35 |
90% CI: [40.11, 51.7]ANOVA
90% CI: [74.11, 98.77]ANOVA
Primary
Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7)
Cmax,ss, Maximum plasma of diclofenac concentration during a dosage interval obtained directly from the concentration-time data at steady state for diclofenac on day 7. Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and gMeans per treatment and race are very similar, only gMeans per treatment and race are presented.
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Population: Pharmacokinetic Population (PK): This population consists of all subjects in the safety population for whom at least one of area under the plasma concentration-time curve over one dosing interval or maximum steady-state plasma drug concentration during a dosage interval could be calculated for one treatment and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac 2% (A) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | Overall | 6.7825 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 100.12 |
| Diclofenac 2% (A) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Black | 9.3923 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 63.72 |
| Diclofenac 2% (A) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Caucasian | 4.7551 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 116.89 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Caucasian | 4.3416 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 55.32 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Black | 7.3863 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 63.86 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | Overall | 5.6964 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 66.98 |
| Voltarol® 2.32% Gel (R) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Black | 14.8040 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 49.82 |
| Voltarol® 2.32% Gel (R) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | By Race: Caucasian | 8.1371 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 71.96 |
| Voltarol® 2.32% Gel (R) | Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7) | Overall | 10.8330 Nanogram/millilitre (ng/mL) | Geometric Coefficient of Variation 70.99 |
90% CI: [43.39, 56.71]ANOVA
90% CI: [66.33, 105.31]ANOVA
Secondary
Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State
Average plasma concentration (Cav,ss) calculated as AUC0-t,ss divided by τ=12 hours (τ is the duration of the dosing interval). Descriptive statistics by race are reported in addition.
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Population: Pharmacokinetic Population (PK): This population consists of all subjects in the safety population for whom at least one of area under the plasma concentration-time curve over one dosing interval or maximum steady-state plasma drug concentration during a dosage interval could be calculated for one treatment and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac 2% (A) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Black | 5.0775 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 58.78 |
| Diclofenac 2% (A) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | Overall | 3.9046 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 66.02 |
| Diclofenac 2% (A) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Caucasian | 2.9317 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 57.46 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Black | 4.4691 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 47.37 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | Overall | 3.3480 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 59.38 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Caucasian | 2.4754 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 51.32 |
| Voltarol® 2.32% Gel (R) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | Overall | 6.9702 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 64.34 |
| Voltarol® 2.32% Gel (R) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Caucasian | 5.6259 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 73.14 |
| Voltarol® 2.32% Gel (R) | Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State | By Race: Black | 8.8055 nanogram/ millilitre (ng/mL) | Geometric Coefficient of Variation 42.13 |
Secondary
Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss]
Percentage peak-trough fluctuation (%PTF) which was calculated as \[100\*(Cmax,ss - Cpre,ss)/Cav,ss\] for Diclofenac. Descriptive statistics by race are reported in addition.
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Population: Pharmacokinetic Population (PK): This population consists of all subjects in the safety population for whom at least one of area under the plasma concentration-time curve over one dosing interval or maximum steady-state plasma drug concentration during a dosage interval could be calculated for one treatment and who had no major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac 2% (A) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Caucasian | 26.75129 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 693.89 |
| Diclofenac 2% (A) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Black | 48.55712 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 96.39 |
| Diclofenac 2% (A) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | Overall | 33.95533 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 354.42 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Caucasian | 39.96865 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 196.93 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | Overall | 26.69620 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 267.21 |
| Diclofenac 2% + Capsaicin 0.075% (B) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Black | 15.07128 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 320.78 |
| Voltarol® 2.32% Gel (R) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Caucasian | 24.25970 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 100.46 |
| Voltarol® 2.32% Gel (R) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | By Race: Black | 25.85257 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 123.16 |
| Voltarol® 2.32% Gel (R) | Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] | Overall | 24.75558 Percentage of Cav,ss (%) | Geometric Coefficient of Variation 103.66 |
Secondary
Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7)
tmax,ss, Time to maximum observed plasma concentration at steady state for diclofenac at day 7 (tmax,ss). Descriptive statistics by race are reported in addition.
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Population: Pharmacokinetic Population (PK): This population consists of all subjects in the safety population for whom at least one of area under the plasma concentration-time curve over one dosing interval or maximum steady-state plasma drug concentration during a dosage interval could be calculated for one treatment and who had no major protocol deviations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Diclofenac 2% (A) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Black | 0.00 Hour (h) |
| Diclofenac 2% (A) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | Overall | 0.75 Hour (h) |
| Diclofenac 2% (A) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Caucasian | 2.00 Hour (h) |
| Diclofenac 2% + Capsaicin 0.075% (B) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Caucasian | 3.50 Hour (h) |
| Diclofenac 2% + Capsaicin 0.075% (B) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | Overall | 1.00 Hour (h) |
| Diclofenac 2% + Capsaicin 0.075% (B) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Black | 0.50 Hour (h) |
| Voltarol® 2.32% Gel (R) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Black | 0.00 Hour (h) |
| Voltarol® 2.32% Gel (R) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | Overall | 0.00 Hour (h) |
| Voltarol® 2.32% Gel (R) | Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7) | By Race: Caucasian | 4.00 Hour (h) |