Trial Outcomes & Findings for A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions (NCT NCT00834288)
NCT ID: NCT00834288
Last Updated: 2012-04-27
Results Overview
Area under the plasma concentration versus time data pairs over 24 hours (24h) at steady state, on day 5. ss = steady state. AUCss is also known as AUCtau.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
24 hours (day 5)
Results posted on
2012-04-27
Participant Flow
Participant milestones
| Measure |
Test (Tramadol HCl OAD 200 mg) First
1 x 200 mg Tramadol OAD (Once-A-Day) Tablet Daily test product dosed in first period followed by Tramadol IR (Ultram®) 50 mg 6-hourly) reference product dosed in the second period. The two treatment phases each started with a run-in period of 4 days (Days 1 to 4), a profile period and clinic stay of 3 days (Days 5 to 7) (clinic days and observation period) and a drug-free period of 16 days between treatment phases (Day 7 of Treatment phase I until Day 1 of the run-in period of Treatment phase II).
|
Reference (Trazodone IR (Desyrel®) 100 mg 8-hourly) First
1 x 100 mg Trazodone HCl IR (Desyrel®) Tablet 8-Hourly reference product dosed in first period followed by Trazodone OAD (Once-A-Day) Tablet Daily test product dosed in the second period. The two periods were separated by a washout of at least 7 calendar days.
IR = Immediate Release.
|
|---|---|---|
|
Treatment Phase I
STARTED
|
13
|
13
|
|
Treatment Phase I
COMPLETED
|
13
|
13
|
|
Treatment Phase I
NOT COMPLETED
|
0
|
0
|
|
Treatment Phase II
STARTED
|
13
|
13
|
|
Treatment Phase II
COMPLETED
|
13
|
13
|
|
Treatment Phase II
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions
Baseline characteristics by cohort
| Measure |
Test (Tramadol HCl OAD 200 mg) First
n=13 Participants
1 x 200 mg Tramadol OAD (Once-A-Day) Tablet Daily test product dosed in first period followed by Tramadol IR (Ultram®) 50 mg 6-hourly) reference product dosed in the second period. The two treatment phases each started with a run-in period of 4 days (Days 1 to 4), a profile period and clinic stay of 3 days (Days 5 to 7) (clinic days and observation period) and a drug-free period of 16 days between treatment phases (Day 7 of Treatment phase I until Day 1 of the run-in period of Treatment phase II).
|
Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First
n=13 Participants
1 x 50 mg Tramadol HCl IR (Ultram®) Tablet 6-Hourly reference product dosed in first period followed by Tramadol OAD (Once-A-Day) Tablet Daily test product dosed in the second period. The two treatment phases each started with a run-in period of 4 days (Days 1 to 4), a profile period and clinic stay of 3 days (Days 5 to 7) (clinic days and observation period) and a drug-free period of 16 days between treatment phases (Day 7 of Treatment phase I until Day 1 of the run-in period of Treatment phase II). IR = Immediate Release.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0.0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26.0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0.0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4.0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22.0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hours (day 5)Area under the plasma concentration versus time data pairs over 24 hours (24h) at steady state, on day 5. ss = steady state. AUCss is also known as AUCtau.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Data Pairs at Steady State (AUCss)
|
5991 ng*h/mL
Standard Deviation 1330
|
6399 ng*h/mL
Standard Deviation 1766
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Maximum plasma concentration over 24 hours (24h) at steady state, on day 5. ss = steady state.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Maximum Plasma Concentration at Steady State(Cmax,ss)
|
345 ng/mL
Standard Deviation 73
|
423 ng/mL
Standard Deviation 97
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Minimum plasma concentration over 24 hours (24h) at steady state on day 5. ss = steady state.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Minimum Plasma Concentration at Steady State(Cmin,ss)
|
157 ng/mL
Standard Deviation 48
|
190 ng/mL
Standard Deviation 64
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Time to peak exposure over 24 hours (24h) at steady state on day 5.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Time to Peak Exposure (Tmax)
|
4 hours
Interval 3.0 to 9.0
|
1 hours
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Percentage peak-trough fluctuation over 24 hours (24h) at steady state on day 5. Percent peak-to-trough fluctuation is calculated as (Cmax - Cmin)/Cav\*100, where Cmax is the maximum observed concentration, Cmin is the minimum observed concentration and Cav is the average concentration over 24 hours (where Cav = AUCss/24).
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Percentage Peak-trough Fluctuation (% PTF)
|
76.9 percentage of fluctuation
Standard Deviation 20.0
|
91.1 percentage of fluctuation
Standard Deviation 20.0
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Percentage swing is a pharmacokinetic parameter recommended by the FDA for submission and is calculated as follows:((Cmax,ss - Cmin,ss)/Cmin,ss)\*100. It was calculated over 24 hours on day 5. Where: Cmax,ss = Maximum concentration at steady state; Cmin,ss = Minimum concentration at steady state.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Percentage Swing
|
131 percentage of fluctuation
Standard Deviation 52
|
133 percentage of fluctuation
Standard Deviation 40
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Time over which plasma concentrations were above one half Cmax on day 5. 24h = 24 hours.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Half-value Duration (HVD)
|
20.7 hours
Standard Deviation 2.56
|
22.0 hours
Standard Deviation 2.24
|
SECONDARY outcome
Timeframe: 24 hours (day 5)Time over which plasma concentrations were above 75% Cmax on day 5. 24h = 24 hours.
Outcome measures
| Measure |
Tramadol HCl OAD 200 mg
n=26 Participants
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 Participants
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Plateau Time (T75%Cmax)
|
11.5 hours
Standard Deviation 4.5
|
9.2 hours
Standard Deviation 3.3
|
Adverse Events
Tramadol HCl OAD 200 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Tramadol IR (Ultram®) 50 mg 6-hourly
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tramadol HCl OAD 200 mg
n=26 participants at risk
Tramadol HCl OAD 200 mg Group includes the treatment period 1 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence and the treatment period 2 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence.
|
Tramadol IR (Ultram®) 50 mg 6-hourly
n=26 participants at risk
Tramadol IR (Ultram®) 50 mg 6-hourly Group includes the treatment period 1 data from subjects in the "Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First" treatment sequence and the treatment period 2 data from subjects in the "Test (Tramadol HCl OAD 200 mg) First" treatment sequence.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
15.4%
4/26 • Number of events 4
|
11.5%
3/26 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
11.5%
3/26 • Number of events 3
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Dry mouth
|
7.7%
2/26 • Number of events 2
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
ALT elevated/raised
|
0.00%
0/26
|
7.7%
2/26 • Number of events 2
|
|
General disorders
Headache
|
19.2%
5/26 • Number of events 5
|
11.5%
3/26 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
11.5%
3/26 • Number of events 4
|
3.8%
1/26 • Number of events 2
|
Additional Information
Director of Regulatory Affairs
Labopharm Inc.
Phone: 1 450 686 1017
Results disclosure agreements
- Principal investigator is a sponsor employee If a publication based on the results of this study is envisaged, approval from the sponsor will be obtained and a draft manuscript will be submitted to the sponsor for scrutiny and comment.
- Publication restrictions are in place
Restriction type: OTHER