Trial Outcomes & Findings for A Bioequivalence Study of Advil PM Liqui-Gels Minis (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) Compared to the Current Marketed Advil PM Liqui-Gels (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) in Healthy Adult Subjects Under Fasted Conditions (NCT NCT05674721)
NCT ID: NCT05674721
Last Updated: 2024-08-23
Results Overview
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen obtained without interpolation. Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
COMPLETED
PHASE1
77 participants
1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
2024-08-23
Participant Flow
This study was conducted at a single center in the United States.
A total of 144 participants were screened of which 77 were enrolled. Of the 77 enrolled participants, 33 were not randomized and 44 were randomized as per cross-over design to one of the two treatment sequences: Sequence AB (Advil PM Liqui-Gels Minis followed by Advil PM Liqui-Gels) or Sequence BA (Advil PM Liqui-Gels followed by Advil PM Liqui-Gels Minis). A total of 42 participants completed the study.
Participant milestones
| Measure |
Sequence AB: Advil PM Liqui-Gels Minis Followed by Advil PM Liqui-Gels
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 milligrams \[mg\]/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment A followed by a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment B. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 milliliters \[mL\]) along with their investigational product.
|
Sequence BA: Advil PM Liqui-Gels Followed by Advil PM Liqui-Gels Minis
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment B followed by a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment A. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along with their investigational product.
|
|---|---|---|
|
Treatment Period 1 (Up to 3 Days)
STARTED
|
22
|
22
|
|
Treatment Period 1 (Up to 3 Days)
COMPLETED
|
22
|
22
|
|
Treatment Period 1 (Up to 3 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout Period (Up to 7 Days)
STARTED
|
22
|
22
|
|
Washout Period (Up to 7 Days)
COMPLETED
|
22
|
20
|
|
Washout Period (Up to 7 Days)
NOT COMPLETED
|
0
|
2
|
|
Treatment Period 2 (Up to 3 Days)
STARTED
|
22
|
20
|
|
Treatment Period 2 (Up to 3 Days)
COMPLETED
|
22
|
20
|
|
Treatment Period 2 (Up to 3 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence AB: Advil PM Liqui-Gels Minis Followed by Advil PM Liqui-Gels
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 milligrams \[mg\]/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment A followed by a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment B. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 milliliters \[mL\]) along with their investigational product.
|
Sequence BA: Advil PM Liqui-Gels Followed by Advil PM Liqui-Gels Minis
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment B followed by a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment A. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along with their investigational product.
|
|---|---|---|
|
Washout Period (Up to 7 Days)
Adverse Event
|
0
|
1
|
|
Washout Period (Up to 7 Days)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Bioequivalence Study of Advil PM Liqui-Gels Minis (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) Compared to the Current Marketed Advil PM Liqui-Gels (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) in Healthy Adult Subjects Under Fasted Conditions
Baseline characteristics by cohort
| Measure |
Sequence AB: Advil PM Liqui-Gels Minis Followed by Advil PM Liqui-Gels
n=22 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment A followed by a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment B. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along with their investigational product.
|
Sequence BA: Advil PM Liqui-Gels Followed by Advil PM Liqui-Gels Minis
n=22 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 1 under fasted conditions as Treatment B followed by a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Period 2 under fasted conditions as Treatment A. There was a washout period of at least 7 days between each dosing. Participants were instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along with their investigational product.
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.1 years
STANDARD_DEVIATION 7.02 • n=5 Participants
|
33.7 years
STANDARD_DEVIATION 9.76 • n=7 Participants
|
33.4 years
STANDARD_DEVIATION 8.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
22 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set included all participants of the PK population who completed both Treatment Periods, and for which the relevant PK parameters (at least one area under the curve \[AUC\] or Cmax) could be derived. The PK population was defined as all randomized participants who had at least one post-dose PK value, and who had no major protocol deviations concerning PKs.
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen obtained without interpolation. Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Ibuprofen
|
36879.50 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 25.2
|
38875.03 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 18.0
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
Cmax was defined as maximum observed post-dose plasma concentration for diphenhydramine obtained without interpolation. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Cmax for Diphenhydramine
|
75.40 ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 40.5
|
73.22 ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 40.0
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to the Last Measurable Sampling Time Point (t) (AUC [0-t]) for Ibuprofen
|
121612.36 hour*nanogram per milliliter (h*ng/ mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 22.3
|
123012.43 hour*nanogram per milliliter (h*ng/ mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 20.7
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
AUC (0-t) for Diphenhydramine
|
746.76 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 49.2
|
728.13 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 49.7
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to Infinity (AUC [0-inf]) for Ibuprofen
|
123067.92 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 22.2
|
124401.36 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 20.7
|
PRIMARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
AUC (0-inf) for Diphenhydramine
|
782.89 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 52.3
|
762.79 h*ng/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported. CV% = 52.7
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
λz was computed as negative of the estimated slope of the linear regression of the ln-transformed concentration versus time profile in the terminal elimination phase. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Terminal Elimination Rate Constant (λz) for Ibuprofen
|
0.3252 1/hour
Standard Deviation 0.05931
|
0.3329 1/hour
Standard Deviation 0.06812
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
λz was computed as the negative of the estimated slope of the linear regression of the ln-transformed concentration versus time profile in the terminal elimination phase. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
λz for Diphenhydramine
|
0.0665 1/hour
Standard Deviation 0.01342
|
0.0669 1/hour
Standard Deviation 0.01277
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
tmax was defined as time of the maximum observed post-dose concentration. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Time of the Maximum Observed Post-dose Concentration (Tmax) for Ibuprofen
|
1.000 hour
Interval 0.25 to 4.75
|
0.875 hour
Interval 0.5 to 3.25
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
tmax was defined as time of the maximum observed post-dose concentration. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Tmax for Diphenhydramine
|
3.000 hour
Interval 1.5 to 5.5
|
3.000 hour
Interval 2.0 to 5.0
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
Elimination half-life was computed as t1/2 = ln(2)/λz where λz is the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
The Elimination Half-life (t1/2) for Ibuprofen
|
2.21 hour
Interval 1.34 to 3.07
|
2.04 hour
Interval 1.49 to 4.4
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
Elimination half-life was computed as t1/2 = ln(2)/λz where λz is the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
t1/2 for Diphenhydramine
|
10.71 hour
Interval 6.29 to 14.41
|
10.45 hour
Interval 6.39 to 14.85
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
Vz/F was calculated by the dose administered/(λz\*AUC0-inf) where λz was the terminal elimination rate constant and AUC0-inf was area under the plasma concentration versus time curve calculated from time 0 to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) for Ibuprofen
|
10.35 liter
Standard Deviation 2.06
|
10.17 liter
Standard Deviation 2.56
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
Vz/F was calculated by the dose administered/(λz\*AUC0-inf) where λz is the terminal elimination rate constant and AUC0-inf is area under the plasma concentration versus time curve calculated from time 0 to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Vz/F for Diphenhydramine
|
1059.73 liter
Standard Deviation 449.56
|
1071.75 liter
Standard Deviation 411.77
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set.
CI/F was calculated as dose administered/AUC0-inf where AUC0-inf was area under the plasma concentration versus time curve calculated from time zero to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Apparent Total Clearance (CI/F) for Ibuprofen
|
3.33 liter per hour
Standard Deviation 0.75
|
3.28 liter per hour
Standard Deviation 0.65
|
SECONDARY outcome
Timeframe: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.
CI/F was calculated as dose administered/ AUC0-inf where AUC0-inf was area under the plasma concentration versus time curve calculated from time zero to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Outcome measures
| Measure |
Treatment A (Test)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=41 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
CI/F for Diphenhydramine
|
71.95 liter per hour
Standard Deviation 37.05
|
72.85 liter per hour
Standard Deviation 33.18
|
SECONDARY outcome
Timeframe: Post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)Population: The safety population.
Immediately after dosing, the assessment of 'ease of swallowing' was done via one question with an ordinal response (ease of swallowing on 5-point ordinal scale) of each product. Participants ranked the 'ease of swallowing' of the product on a scale from 1 to 5 where 1=not easy to swallow; 2=somewhat easy to swallow; 3=average to swallow; 4=above average to swallow; 5=very easy to swallow. Higher score indicated more ease in swallowing.
Outcome measures
| Measure |
Treatment A (Test)
n=42 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=44 Participants
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
3 (Average to Swallow)
|
0 Participants
|
1 Participants
|
|
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
1 (Not Easy to Swallow)
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
2 (Somewhat Easy to Swallow)
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
4 (Above Average to Swallow)
|
1 Participants
|
3 Participants
|
|
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
5 (Very Easy to Swallow)
|
41 Participants
|
40 Participants
|
Adverse Events
Treatment A (Test)
Treatment B (Reference)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A (Test)
n=42 participants at risk
Participants received a single dose of 2 Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment A.
|
Treatment B (Reference)
n=44 participants at risk
Participants received a single dose of 2 Advil PM Liqui-Gels (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg), capsules, orally on Day 1 of Treatment Periods 1 and 2 under fasted conditions as Treatment B.
|
|---|---|---|
|
Investigations
Haemoglobin decreased
|
0.00%
0/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
2.3%
1/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
Investigations
SARS-CoV-2 test positive
|
0.00%
0/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
2.3%
1/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
Investigations
White blood cell count increased
|
0.00%
0/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
2.3%
1/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
Nervous system disorders
Presyncope
|
2.4%
1/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
4.5%
2/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
General disorders
Catheter site pain
|
2.4%
1/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
0.00%
0/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
0.00%
0/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
2.3%
1/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.4%
1/42 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
0.00%
0/44 • From screening up to end of study (up to 38 days)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product (or medical device), whether or not considered related to the study product, including any washout or lead-in product (or medical device). A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse outcome is serious.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee HALEON agreements may vary with individual investigators but will not prohibit any investigator from publishing. HALEON supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER