Trial Outcomes & Findings for Comparison of the Bioavailability of Diclofenac in 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, in Healthy Volunteers (NCT NCT03074162)
NCT ID: NCT03074162
Last Updated: 2019-03-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
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
Results posted on
2019-03-01
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Period 1 Including Washout 1
STARTED
|
8
|
8
|
8
|
8
|
8
|
8
|
|
Period 1 Including Washout 1
COMPLETED
|
8
|
8
|
7
|
8
|
8
|
8
|
|
Period 1 Including Washout 1
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 2 Including Washout 2
STARTED
|
8
|
8
|
7
|
8
|
8
|
8
|
|
Period 2 Including Washout 2
COMPLETED
|
8
|
8
|
6
|
8
|
8
|
7
|
|
Period 2 Including Washout 2
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
1
|
|
Period 3
STARTED
|
8
|
8
|
6
|
8
|
8
|
7
|
|
Period 3
COMPLETED
|
7
|
8
|
6
|
8
|
7
|
7
|
|
Period 3
NOT COMPLETED
|
1
|
0
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
Safety Population
Baseline characteristics by cohort
| Measure |
A-B-R
n=8 Participants
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.
|
B-R-A
n=8 Participants
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.
|
R-A-B
n=8 Participants
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.
|
R-B-A
n=8 Participants
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.
|
A-R-B
n=8 Participants
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.
|
B-A-R
n=8 Participants
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.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
30.9 Years
STANDARD_DEVIATION 9.43 • n=39 Participants • Safety Population
|
29.4 Years
STANDARD_DEVIATION 10.04 • n=41 Participants • Safety Population
|
27.6 Years
STANDARD_DEVIATION 7.84 • n=35 Participants • Safety Population
|
28.5 Years
STANDARD_DEVIATION 8.82 • n=31 Participants • Safety Population
|
22.5 Years
STANDARD_DEVIATION 3.38 • n=146 Participants • Safety Population
|
26.0 Years
STANDARD_DEVIATION 8.16 • n=19 Participants • Safety Population
|
27.5 Years
STANDARD_DEVIATION 8.24 • n=147 Participants • Safety Population
|
|
Sex: Female, Male
Female
|
1 Participants
n=39 Participants • Safety Population
|
2 Participants
n=41 Participants • Safety Population
|
4 Participants
n=35 Participants • Safety Population
|
3 Participants
n=31 Participants • Safety Population
|
1 Participants
n=146 Participants • Safety Population
|
3 Participants
n=19 Participants • Safety Population
|
14 Participants
n=147 Participants • Safety Population
|
|
Sex: Female, Male
Male
|
7 Participants
n=39 Participants • Safety Population
|
6 Participants
n=41 Participants • Safety Population
|
4 Participants
n=35 Participants • Safety Population
|
5 Participants
n=31 Participants • Safety Population
|
7 Participants
n=146 Participants • Safety Population
|
5 Participants
n=19 Participants • Safety Population
|
34 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants • Safety Population
|
0 Participants
n=41 Participants • Safety Population
|
0 Participants
n=35 Participants • Safety Population
|
0 Participants
n=31 Participants • Safety Population
|
0 Participants
n=146 Participants • Safety Population
|
0 Participants
n=19 Participants • Safety Population
|
0 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants • Safety Population
|
0 Participants
n=41 Participants • Safety Population
|
0 Participants
n=35 Participants • Safety Population
|
0 Participants
n=31 Participants • Safety Population
|
0 Participants
n=146 Participants • Safety Population
|
0 Participants
n=19 Participants • Safety Population
|
0 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants • Safety Population
|
0 Participants
n=41 Participants • Safety Population
|
0 Participants
n=35 Participants • Safety Population
|
0 Participants
n=31 Participants • Safety Population
|
0 Participants
n=146 Participants • Safety Population
|
0 Participants
n=19 Participants • Safety Population
|
0 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=39 Participants • Safety Population
|
4 Participants
n=41 Participants • Safety Population
|
4 Participants
n=35 Participants • Safety Population
|
4 Participants
n=31 Participants • Safety Population
|
4 Participants
n=146 Participants • Safety Population
|
4 Participants
n=19 Participants • Safety Population
|
24 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
White
|
4 Participants
n=39 Participants • Safety Population
|
4 Participants
n=41 Participants • Safety Population
|
4 Participants
n=35 Participants • Safety Population
|
4 Participants
n=31 Participants • Safety Population
|
4 Participants
n=146 Participants • Safety Population
|
4 Participants
n=19 Participants • Safety Population
|
24 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants • Safety Population
|
0 Participants
n=41 Participants • Safety Population
|
0 Participants
n=35 Participants • Safety Population
|
0 Participants
n=31 Participants • Safety Population
|
0 Participants
n=146 Participants • Safety Population
|
0 Participants
n=19 Participants • Safety Population
|
0 Participants
n=147 Participants • Safety Population
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants • Safety Population
|
0 Participants
n=41 Participants • Safety Population
|
0 Participants
n=35 Participants • Safety Population
|
0 Participants
n=31 Participants • Safety Population
|
0 Participants
n=146 Participants • Safety Population
|
0 Participants
n=19 Participants • Safety Population
|
0 Participants
n=147 Participants • Safety Population
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Diclofenac 2% (A)
n=47 Participants
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 Participants
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 Participants
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
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
|
40.175 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 59.38
|
83.644 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 64.35
|
|
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
|
53.628 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 47.37
|
105.670 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 42.13
|
|
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
|
29.704 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 51.32
|
67.513 Hour*nanogram/millilitre (h*ng/mL)
Geometric Coefficient of Variation 73.15
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Diclofenac 2% (A)
n=47 Participants
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 Participants
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 Participants
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
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
|
5.6964 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 66.98
|
10.8330 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 70.99
|
|
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
|
7.3863 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 63.86
|
14.8040 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 49.82
|
|
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
|
4.3416 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 55.32
|
8.1371 Nanogram/millilitre (ng/mL)
Geometric Coefficient of Variation 71.96
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Diclofenac 2% (A)
n=47 Participants
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 Participants
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 Participants
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7)
Overall
|
0.75 Hour (h)
Interval 0.0 to 12.0
|
1.00 Hour (h)
Interval 0.0 to 12.0
|
0.00 Hour (h)
Interval 0.0 to 12.0
|
|
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)
Interval 0.0 to 10.0
|
0.50 Hour (h)
Interval 0.0 to 10.02
|
0.00 Hour (h)
Interval 0.0 to 8.0
|
|
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)
Interval 0.0 to 12.0
|
3.50 Hour (h)
Interval 0.0 to 12.0
|
4.00 Hour (h)
Interval 0.0 to 12.0
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Diclofenac 2% (A)
n=46 Participants
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 Participants
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 Participants
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State
Overall
|
3.9046 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 66.02
|
3.3480 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 59.38
|
6.9702 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 64.34
|
|
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
|
4.4691 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 47.37
|
8.8055 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 42.13
|
|
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
|
2.4754 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 51.32
|
5.6259 nanogram/ millilitre (ng/mL)
Geometric Coefficient of Variation 73.14
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Diclofenac 2% (A)
n=47 Participants
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 Participants
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 Participants
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
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
|
26.69620 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 267.21
|
24.75558 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 103.66
|
|
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
|
15.07128 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 320.78
|
25.85257 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 123.16
|
|
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
|
39.96865 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 196.93
|
24.25970 Percentage of Cav,ss (%)
Geometric Coefficient of Variation 100.46
|
Adverse Events
Diclofenac 2% (A)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Diclofenac 2% + Capsaicin 0.075% (B)
Serious events: 0 serious events
Other events: 44 other events
Deaths: 0 deaths
Voltarol® 2.32% Gel (R)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diclofenac 2% (A)
n=47 participants at risk
Subjects were administered 2 grams of Diclofenac 2% immediate release topical mono gel twice daily for 6 days and only once in the morning on Day 7.
|
Diclofenac 2% + Capsaicin 0.075% (B)
n=46 participants at risk
Subjects were administered 2 grams of Combination of Diclofenac 2% and Capsaicin 0.075% immediate release topical gel twice daily for 6 days and only once in the morning on Day 7.
|
Voltarol® 2.32% Gel (R)
n=47 participants at risk
Subjects were administered 2 grams of Voltarol® Emulgel 2.32% Gel with 2.32% diclofenac topical gel twice daily for 6 days and only once in the morning on Day 7.
|
|---|---|---|---|
|
General disorders
Application site dryness
|
4.3%
2/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
6.5%
3/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
|
General disorders
Application site erythema
|
6.4%
3/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
|
General disorders
Application site inflammation
|
4.3%
2/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
95.7%
44/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
|
General disorders
Application site pruritus
|
12.8%
6/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
6.5%
3/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
4.3%
2/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
6.5%
3/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
|
Nervous system disorders
Headache
|
0.00%
0/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
0.00%
0/46 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
6.4%
3/47 • From first drug administration until individual subject's end of study, up to approximately 38 days.
Safety Population (All subjects who received at least one dose of study medication were included in the safety population) was used for safety analysis.
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER