Trial Outcomes & Findings for A Four-Period, Four-Treatment, Four-Way Relative Bioavailability Study of CL-108 Under Fed and Fasted Conditions (NCT NCT02465866)
NCT ID: NCT02465866
Last Updated: 2017-05-02
Results Overview
Cmax of CL-108 and Vicoprofen + Ultracet + Phenergan were measured in the plasma (the liquid component of the blood in which the blood cells are suspended) in samples collected up to 48 hours post-dose.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Results posted on
2017-05-02
Participant Flow
Twenty healthy subjects were enrolled in the study.
Participant milestones
| Measure |
Sequence 1: ABDC
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 2: BCAD
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 3: CDBA
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 4: DACB
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Dosing in 4 study periods was separated by a 14-day washout period
|
|---|---|---|---|---|
|
Period 1
STARTED
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5
|
5
|
5
|
5
|
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Period 1
COMPLETED
|
5
|
5
|
5
|
5
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 1: Washout (14 Days)
STARTED
|
5
|
5
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5
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5
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Period 1: Washout (14 Days)
COMPLETED
|
5
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5
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5
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5
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Period 1: Washout (14 Days)
NOT COMPLETED
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0
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0
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0
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0
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Period 2
STARTED
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5
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5
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5
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5
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Period 2
COMPLETED
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5
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5
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5
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5
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Period 2
NOT COMPLETED
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0
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0
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0
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0
|
|
Period 2: Washout (14 Days)
STARTED
|
5
|
5
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5
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5
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Period 2: Washout (14 Days)
COMPLETED
|
5
|
5
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5
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5
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|
Period 2: Washout (14 Days)
NOT COMPLETED
|
0
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0
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0
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0
|
|
Period 3
STARTED
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5
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5
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5
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5
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Period 3
COMPLETED
|
5
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4
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5
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5
|
|
Period 3
NOT COMPLETED
|
0
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1
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0
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0
|
|
Period 3: Washout (14 Days)
STARTED
|
5
|
4
|
5
|
5
|
|
Period 3: Washout (14 Days)
COMPLETED
|
5
|
4
|
5
|
5
|
|
Period 3: Washout (14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
5
|
4
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5
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5
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Period 4
COMPLETED
|
5
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4
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5
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5
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Period 4
NOT COMPLETED
|
0
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0
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0
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0
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|
Period 4: Washout (14 Days)
STARTED
|
5
|
4
|
5
|
5
|
|
Period 4: Washout (14 Days)
COMPLETED
|
5
|
4
|
5
|
5
|
|
Period 4: Washout (14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: ABDC
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 2: BCAD
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 3: CDBA
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Dosing in 4 study periods was separated by a 14-day washout period
|
Sequence 4: DACB
Treatment D: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
Treatment A: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
Treatment C: Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
Treatment B: CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
Dosing in 4 study periods was separated by a 14-day washout period
|
|---|---|---|---|---|
|
Period 3
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Four-Period, Four-Treatment, Four-Way Relative Bioavailability Study of CL-108 Under Fed and Fasted Conditions
Baseline characteristics by cohort
| Measure |
Overall Subjects
n=20 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
52.85 years
STANDARD_DEVIATION 17.71 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
|
Height
|
163.15 cm
STANDARD_DEVIATION 10.49 • n=5 Participants
|
|
Weight
|
67.83 kg
STANDARD_DEVIATION 10.72 • n=5 Participants
|
|
Body Mass Index (BMI)
|
25.43 kg/m²
STANDARD_DEVIATION 2.80 • n=5 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: Intended to treat (ITT) population
Cmax of CL-108 and Vicoprofen + Ultracet + Phenergan were measured in the plasma (the liquid component of the blood in which the blood cells are suspended) in samples collected up to 48 hours post-dose.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data
Hydrocodone
|
20.0 ng/mL
Standard Deviation 5.48
|
17.9 ng/mL
Standard Deviation 5.80
|
18.4 ng/mL
Standard Deviation 5.62
|
17.5 ng/mL
Standard Deviation 3.63
|
|
Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data
Acetaminophen
|
4.71 ng/mL
Standard Deviation 1.49
|
3.27 ng/mL
Standard Deviation 1.00
|
5.02 ng/mL
Standard Deviation 1.66
|
3.03 ng/mL
Standard Deviation 0.919
|
|
Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data
Promethazine (Number of Participants=19,19,20,19)
|
4.79 ng/mL
Standard Deviation 3.75
|
3.66 ng/mL
Standard Deviation 2.16
|
4.35 ng/mL
Standard Deviation 2.94
|
4.08 ng/mL
Standard Deviation 1.95
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Time to Reach Maximum Concentration (Tmax)
Hydrocodone
|
1.55 hours
Standard Deviation 0.71
|
3.38 hours
Standard Deviation 1.58
|
1.39 hours
Standard Deviation 1.22
|
3.09 hours
Standard Deviation 1.89
|
|
Time to Reach Maximum Concentration (Tmax)
Acetaminophen
|
0.91 hours
Standard Deviation 0.44
|
2.84 hours
Standard Deviation 1.49
|
0.80 hours
Standard Deviation 0.55
|
2.64 hours
Standard Deviation 1.44
|
|
Time to Reach Maximum Concentration (Tmax)
Promethazine (Number of Participants=19,19,20,19)
|
4.35 hours
Standard Deviation 1.37
|
5.24 hours
Standard Deviation 2.37
|
4.90 hours
Standard Deviation 1.72
|
6.45 hours
Standard Deviation 4.59
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data
Hydrocodone
|
0.556 ng/mL
Standard Deviation 0.354
|
0.523 ng/mL
Standard Deviation 0.412
|
0.465 ng/mL
Standard Deviation 0.315
|
0.527 ng/mL
Standard Deviation 0.424
|
|
Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data
Acetaminophen
|
0.0741 ng/mL
Standard Deviation 0.0297
|
0.0917 ng/mL
Standard Deviation 0.0378
|
0.0724 ng/mL
Standard Deviation 0.0291
|
0.0907 ng/mL
Standard Deviation 0.0428
|
|
Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data
Promethazine (Number of Participants=19,19,20,19)
|
0.611 ng/mL
Standard Deviation 0.936
|
0.586 ng/mL
Standard Deviation 1.04
|
0.574 ng/mL
Standard Deviation 0.829
|
0.701 ng/mL
Standard Deviation 0.912
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Time of the Last Quantifiable Concentration (Tlast)
Promethazine (Number of Participants=19,19,20,19)
|
46.76 Hours
Standard Deviation 5.51
|
46.77 Hours
Standard Deviation 5.52
|
46.81 Hours
Standard Deviation 5.37
|
46.74 Hours
Standard Deviation 5.51
|
|
Time of the Last Quantifiable Concentration (Tlast)
Hydrocodone
|
27.80 Hours
Standard Deviation 8.99
|
31.21 Hours
Standard Deviation 11.28
|
28.81 Hours
Standard Deviation 9.84
|
31.58 Hours
Standard Deviation 11.46
|
|
Time of the Last Quantifiable Concentration (Tlast)
Acetaminophen
|
23.38 Hours
Standard Deviation 2.76
|
24.01 Hours
Standard Deviation 0.04
|
23.41 Hours
Standard Deviation 2.69
|
24.01 Hours
Standard Deviation 0.02
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Estimated by linear regression through at least three data points in the terminal phase of the log concentration-time profile
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Observed Elimination Rate Constant (λz)
Acetaminophen
|
0.1577 h-1
Standard Deviation 0.0310
|
0.1359 h-1
Standard Deviation 0.0223
|
0.1600 h-1
Standard Deviation 0.0355
|
0.1412 h-1
Standard Deviation 0.0218
|
|
Observed Elimination Rate Constant (λz)
Promethazine (Number of Participants=19,18,20,18)
|
0.0429 h-1
Standard Deviation 0.0129
|
0.0451 h-1
Standard Deviation 0.0451
|
0.0422 h-1
Standard Deviation 0.0120
|
0.0458 h-1
Standard Deviation 0.0145
|
|
Observed Elimination Rate Constant (λz)
Hydrocodone
|
0.1468 h-1
Standard Deviation 0.0293
|
0.1373 h-1
Standard Deviation 0.0258
|
0.1415 h-1
Standard Deviation 0.0292
|
0.1371 h-1
Standard Deviation 0.0271
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Calculated as: T1/2 = ln(2)/λz
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Observed Terminal Elimination Half-life (T1/2)
Hydrocodone
|
4.93 hours
Standard Deviation 1.11
|
5.22 hours
Standard Deviation 0.99
|
5.13 hours
Standard Deviation 1.18
|
5.26 hours
Standard Deviation 1.08
|
|
Observed Terminal Elimination Half-life (T1/2)
Acetaminophen
|
4.59 hours
Standard Deviation 1.06
|
5.22 hours
Standard Deviation 0.79
|
4.52 hours
Standard Deviation 0.93
|
5.03 hours
Standard Deviation 0.86
|
|
Observed Terminal Elimination Half-life (T1/2)
Promethazine (Number of Participants=19,18,20,18)
|
17.49 hours
Standard Deviation 5.21
|
15.95 hours
Standard Deviation 3.04
|
17.77 hours
Standard Deviation 5.57
|
16.24 hours
Standard Deviation 4.09
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 0.25 hours post-dosePopulation: ITT population
AUC0-0.25 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine
Hydrocodone
|
0.08870 h*ng/mL
Standard Deviation 0.1318
|
0.03786 h*ng/mL
Standard Deviation 0.1269
|
0.1219 h*ng/mL
Standard Deviation 0.2151
|
0.02250 h*ng/mL
Standard Deviation 0.04577
|
|
Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
0.01086 h*ng/mL
Standard Deviation 0.03169
|
0.003941 h*ng/mL
Standard Deviation 0.01413
|
0.006288 h*ng/mL
Standard Deviation 0.02608
|
0.002612 h*ng/mL
Standard Deviation 0.01138
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 0.5 hours post-dosePopulation: ITT population
AUC0-0.50 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-0.50 for Hydrocodone and Promethazine
Hydrocodone
|
0.9532 h*ng/mL
Standard Deviation 0.9498
|
0.2566 h*ng/mL
Standard Deviation 0.6382
|
1.280 h*ng/mL
Standard Deviation 1.271
|
0.3163 h*ng/mL
Standard Deviation 0.4305
|
|
AUC0-0.50 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
0.03535 h*ng/mL
Standard Deviation 0.06239
|
0.01570 h*ng/mL
Standard Deviation 0.03508
|
0.02692 h*ng/mL
Standard Deviation 0.06096
|
0.01220 h*ng/mL
Standard Deviation 0.02452
|
PRIMARY outcome
Timeframe: 0 (Pre-dose) to 0.75 hours post-dosePopulation: ITT population
AUC0-0.75 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-0.75 for Hydrocodone and Promethazine
Hydrocodone
|
3.194 h*ng/mL
Standard Deviation 2.379
|
0.8759 h*ng/mL
Standard Deviation 1.645
|
4.027 h*ng/mL
Standard Deviation 3.092
|
1.276 h*ng/mL
Standard Deviation 1.629
|
|
AUC0-0.75 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
0.1108 h*ng/mL
Standard Deviation 0.1090
|
0.05549 h*ng/mL
Standard Deviation 0.08128
|
0.09690 h*ng/mL
Standard Deviation 0.1478
|
0.04610 h*ng/mL
Standard Deviation 0.06227
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 1.0 hours post-dosePopulation: ITT population
AUC0-1.0 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-1.0 for Hydrocodone and Promethazine
Hydrocodone
|
6.383 h*ng/mL
Standard Deviation 3.637
|
2.046 h*ng/mL
Standard Deviation 3.244
|
7.524 h*ng/mL
Standard Deviation 4.678
|
2.722 h*ng/mL
Standard Deviation 3.329
|
|
AUC0-1.0 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
0.2578 h*ng/mL
Standard Deviation 0.1999
|
0.1457 h*ng/mL
Standard Deviation 0.1649
|
0.2311 h*ng/mL
Standard Deviation 0.3055
|
0.1109 h*ng/mL
Standard Deviation 0.1471
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 1.5 hours post-dosePopulation: ITT population
AUC0-1.5 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-1.5 for Hydrocodone and Promethazine
Hydrocodone
|
14.33 h*ng/mL
Standard Deviation 4.971
|
5.782 h*ng/mL
Standard Deviation 7.049
|
14.95 h*ng/mL
Standard Deviation 6.822
|
6.424 h*ng/mL
Standard Deviation 6.742
|
|
AUC0-1.5 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
0.8524 h*ng/mL
Standard Deviation 0.5410
|
0.5573 h*ng/mL
Standard Deviation 0.4798
|
0.7330 h*ng/mL
Standard Deviation 0.8395
|
0.3239 h*ng/mL
Standard Deviation 0.3643
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 2 hours post-dosePopulation: ITT population
AUC0-2.0 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-2.0 for Hydrocodone and Promethazine
Hydrocodone
|
23.21 h*ng/mL
Standard Deviation 6.240
|
10.95 h*ng/mL
Standard Deviation 10.34
|
22.53 h*ng/mL
Standard Deviation 8.183
|
11.04 h*ng/mL
Standard Deviation 10.12
|
|
AUC0-2.0 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
1.938 h*ng/mL
Standard Deviation 1.318
|
1.267 h*ng/mL
Standard Deviation 0.9936
|
1.583 h*ng/mL
Standard Deviation 1.689
|
0.6735 h*ng/mL
Standard Deviation 0.6328
|
PRIMARY outcome
Timeframe: 0 (pre-dose) to 4 hours post-dosePopulation: ITT population
AUC0-4.0 measured by Linear Trapezoidal with Linear Interpolation method.
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
AUC0-4.0 for Hydrocodone and Promethazine
Hydrocodone
|
54.04 h*ng/mL
Standard Deviation 13.77
|
38.97 h*ng/mL
Standard Deviation 18.47
|
48.35 h*ng/mL
Standard Deviation 12.87
|
35.14 h*ng/mL
Standard Deviation 17.97
|
|
AUC0-4.0 for Hydrocodone and Promethazine
Promethazine (Number of Participants=19,19,20,19)
|
9.124 h*ng/mL
Standard Deviation 6.271
|
5.943 h*ng/mL
Standard Deviation 3.676
|
7.101 h*ng/mL
Standard Deviation 6.159
|
4.045 h*ng/mL
Standard Deviation 2.497
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Calculated using the linear trapezoidal rule
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration
Hydrocodone
|
146.2 h*ng/mL
Standard Deviation 56.77
|
151.9 h*ng/mL
Standard Deviation 58.79
|
130.9 h*ng/mL
Standard Deviation 47.94
|
148.5 h*ng/mL
Standard Deviation 56.84
|
|
Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration
Acetaminophen
|
19.19 h*ng/mL
Standard Deviation 5.661
|
17.85 h*ng/mL
Standard Deviation 4.621
|
18.69 h*ng/mL
Standard Deviation 5.186
|
17.85 h*ng/mL
Standard Deviation 4.742
|
|
Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration
Promethazine (Number of Participants=19,19,20,19)
|
75.69 h*ng/mL
Standard Deviation 78.87
|
66.63 h*ng/mL
Standard Deviation 67.37
|
68.54 h*ng/mL
Standard Deviation 63.24
|
74.76 h*ng/mL
Standard Deviation 57.53
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Calculated as: AUCinf = AUClast + Clast/λz
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity
Hydrocodone
|
150.2 h*ng/mL
Standard Deviation 57.30
|
155.8 h*ng/mL
Standard Deviation 58.75
|
134.3 h*ng/mL
Standard Deviation 48.20
|
152.4 h*ng/mL
Standard Deviation 56.83
|
|
Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity
Promethazine (Number of Participants=19,18,20,18)
|
96.92 h*ng/mL
Standard Deviation 119.5
|
60.72 h*ng/mL
Standard Deviation 29.74
|
88.53 h*ng/mL
Standard Deviation 100.3
|
84.13 h*ng/mL
Standard Deviation 76.72
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dosePopulation: ITT population
Calculated as: AUCExtrap (%) = (AUC0-inf - AUC0-last)/AUC0-inf \*100
Outcome measures
| Measure |
Treatment A: CL-108 (Fasted)
n=19 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 Participants
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 Participants
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation
Hydrocodone
|
2.72 Percentage of AUCExtrap
Standard Deviation 1.72
|
2.68 Percentage of AUCExtrap
Standard Deviation 1.97
|
2.65 Percentage of AUCExtrap
Standard Deviation 1.78
|
2.71 Percentage of AUCExtrap
Standard Deviation 2.06
|
|
Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation
Promethazine (Number of Participants=19,18,20,18)
|
14.35 Percentage of AUCExtrap
Standard Deviation 7.03
|
13.54 Percentage of AUCExtrap
Standard Deviation 4.64
|
15.15 Percentage of AUCExtrap
Standard Deviation 7.86
|
14.56 Percentage of AUCExtrap
Standard Deviation 6.28
|
Adverse Events
Treatment A: CL-108 (Fasted)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment B: CL-108 (Fed)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: CL-108 (Fasted)
n=19 participants at risk
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition
|
Treatment B: CL-108 (Fed)
n=20 participants at risk
CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition
|
Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)
n=20 participants at risk
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition
|
Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)
n=19 participants at risk
Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/19 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Gastrointestinal disorders
Dry mouth
|
5.3%
1/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Gastrointestinal disorders
Glossodynia
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Up to day 72
|
10.0%
2/20 • Up to day 72
|
20.0%
4/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Gastrointestinal disorders
Oral pruritus
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
15.0%
3/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Nervous system disorders
Headache
|
0.00%
0/19 • Up to day 72
|
10.0%
2/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Nervous system disorders
Somnolence
|
0.00%
0/19 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
10.0%
2/20 • Up to day 72
|
10.5%
2/19 • Up to day 72
|
|
Psychiatric disorders
Euphoric mood
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/19 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Vascular disorders
Hot flush
|
0.00%
0/19 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
10.0%
2/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Vascular disorders
Hypotension
|
0.00%
0/19 • Up to day 72
|
10.0%
2/20 • Up to day 72
|
15.0%
3/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/19 • Up to day 72
|
5.0%
1/20 • Up to day 72
|
0.00%
0/20 • Up to day 72
|
0.00%
0/19 • Up to day 72
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place