Trial Outcomes & Findings for A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily) (NCT NCT01121900)
NCT ID: NCT01121900
Last Updated: 2012-04-27
Results Overview
Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
68 hours
Results posted on
2012-04-27
Participant Flow
Participant milestones
| Measure |
Test (Trazodone Contramid® OAD) First
Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet once daily) dosed in first treatment phase followed by Trazodone IR (Apotex Corp.) reference product (100 mg tablet thrice daily) dosed in the second treatment phase. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in treatment period 1 and the first administration of study medication in treatment period 2.
IR = Immediate Release.
|
Reference (Trazodone IR [Apotex Corp.]) First
Trazodone IR (Apotex Corp.) reference product (100 mg tablet thrice daily) dosed in first treatment phase followed by Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet once daily) dosed in the second treatment phase. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in treatment period 1 and the first administration of study medication in treatment period 2.
IR = Immediate Release.
|
|---|---|---|
|
First Intervention Period
STARTED
|
13
|
13
|
|
First Intervention Period
COMPLETED
|
12
|
12
|
|
First Intervention Period
NOT COMPLETED
|
1
|
1
|
|
Washout Period of 7 Days
STARTED
|
12
|
12
|
|
Washout Period of 7 Days
COMPLETED
|
12
|
11
|
|
Washout Period of 7 Days
NOT COMPLETED
|
0
|
1
|
|
Second Intervention Period
STARTED
|
12
|
11
|
|
Second Intervention Period
COMPLETED
|
12
|
11
|
|
Second Intervention Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Test (Trazodone Contramid® OAD) First
Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet once daily) dosed in first treatment phase followed by Trazodone IR (Apotex Corp.) reference product (100 mg tablet thrice daily) dosed in the second treatment phase. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in treatment period 1 and the first administration of study medication in treatment period 2.
IR = Immediate Release.
|
Reference (Trazodone IR [Apotex Corp.]) First
Trazodone IR (Apotex Corp.) reference product (100 mg tablet thrice daily) dosed in first treatment phase followed by Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet once daily) dosed in the second treatment phase. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in treatment period 1 and the first administration of study medication in treatment period 2.
IR = Immediate Release.
|
|---|---|---|
|
First Intervention Period
Adverse Event
|
1
|
1
|
|
Washout Period of 7 Days
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily)
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=26 Participants
Includes groups randomized to receive Test first and Reference first.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
|
Age Continuous
|
25.2 years
STANDARD_DEVIATION 10.88 • n=39 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=39 Participants
|
|
Region of Enrollment
South Africa
|
26 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Bioequivalence Based Cmax
|
1230.7 ng/mL
Standard Deviation 499.1
|
2947.7 ng/mL
Standard Deviation 734.7
|
PRIMARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
AUC(0-tlast) = Area under the plasma concentration curve (AUC) vs (versus) time data pairs, where tlast is the time of the last quantifiable concentration. Measured in nanogram x hours per milliliter (ng\*h/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Bioequivalence Based on AUC(0-tlast)
|
28138.4 hr*ng/mL
Standard Deviation 8400.0
|
34272.4 hr*ng/mL
Standard Deviation 9792.8
|
PRIMARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
AUC(0-∞) = Area under the plasma concentration curve vs time data pairs, with extrapolation to infinity (∞). Measured in nanogram x hours per milliliter (ng\*h/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Bioequivalence Based on AUC(0-∞)
|
29672.5 h*ng/mL
Standard Deviation 8373.8
|
35258.5 h*ng/mL
Standard Deviation 10067.4
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]
|
18331.0 h*ng/mL
Standard Deviation 4966.4
|
24602.2 h*ng/mL
Standard Deviation 6097.5
|
SECONDARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)
|
9.00 Hours
Full Range 3.64 • Interval 2.0 to 16.02
|
8.33 Hours
Full Range 1.66 • Interval 8.33 to 16.33
|
SECONDARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
The elimination rate constant of trazodone (Lamda z). It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour. This constant is used in half-life calculations.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λz)
|
0.064 1/hour
Standard Deviation 0.018
|
0.090 1/hour
Standard Deviation 0.024
|
SECONDARY outcome
Timeframe: 68 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.
The elimination half-life (T½z) of trazodone in plasma (time it takes for the concentration of trazodone to fall to half), expressed in hours.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=23 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=23 Participants
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Apparent Terminal Half-life (t½.z)
|
11.8 Hours
Standard Deviation 3.7
|
8.3 Hours
Standard Deviation 2.5
|
Adverse Events
Trazodone Contramid® OAD
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Trazodone IR (Apotex Corp.)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Trazodone Contramid® OAD
n=24 participants at risk
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone IR (Apotex Corp.)
n=25 participants at risk
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily)dosed in either first intervention period or second intervention period. A drug-free period of 7 to 14 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
20.8%
5/24 • Number of events 6
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
16.0%
4/25 • Number of events 5
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
12.0%
3/25 • Number of events 3
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
|
Gastrointestinal disorders
Nausea
|
16.7%
4/24 • Number of events 6
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
8.0%
2/25 • Number of events 2
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
|
Gastrointestinal disorders
Vomiting
|
4.2%
1/24 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
4.0%
1/25 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
|
General disorders
Oedema peripheral
|
4.2%
1/24 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
4.0%
1/25 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.2%
1/24 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
4.0%
1/25 • Number of events 1
A total of 24 subjects were exposed to Trazodone Contramid® OAD during the study (13 during first intervention period and 11 during second intervention period). A total of 25 subjects were exposed to Trazodone IR (Apotex Corp.) during the study (13 during first intervention period and 12 during second intervention period).
|
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. The choice of scientific journal will be mutually agreed on by the principal investigator and the sponsor.
- Publication restrictions are in place
Restriction type: OTHER