Trial Outcomes & Findings for Comparative Bioavailability Study of Two Prototypes of Trazodone Controlled-release Products and Two Marketed Reference Products in Healthy Volunteers (NCT NCT01121913)
NCT ID: NCT01121913
Last Updated: 2012-04-27
Results Overview
AUC(0-t) = Area under the plasma concentration curve vs (versus) time data pairs, where t is the time of the last quantifiable concentration. Measured in nanogram x hours per milliliter (ng\*h/mL).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
72 hours
Results posted on
2012-04-27
Participant Flow
Participant milestones
| Measure |
Trazodone Contramid® OAD (Prototype 1) First
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase I; followed by 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase II; 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase III; and 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Trazodone Contramid® OAD (Prototype 2) First
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase I, followed by 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase II; 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase III; and 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Triticco® First
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase I; followed by 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase II; 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase III; and 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Desyrel® First
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase I; followed by 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase II; 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase III; and 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
|---|---|---|---|---|
|
First Intervention Period
STARTED
|
6
|
6
|
6
|
6
|
|
First Intervention Period
COMPLETED
|
6
|
6
|
5
|
6
|
|
First Intervention Period
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
First Washout Period
STARTED
|
6
|
6
|
5
|
6
|
|
First Washout Period
COMPLETED
|
5
|
6
|
5
|
6
|
|
First Washout Period
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Second Intervention Period
STARTED
|
5
|
6
|
5
|
6
|
|
Second Intervention Period
COMPLETED
|
5
|
6
|
4
|
6
|
|
Second Intervention Period
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Second Washout Period
STARTED
|
5
|
6
|
4
|
6
|
|
Second Washout Period
COMPLETED
|
5
|
6
|
3
|
6
|
|
Second Washout Period
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Third Intervention Period
STARTED
|
5
|
6
|
3
|
6
|
|
Third Intervention Period
COMPLETED
|
5
|
6
|
3
|
6
|
|
Third Intervention Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Third Washout Period
STARTED
|
5
|
6
|
3
|
6
|
|
Third Washout Period
COMPLETED
|
4
|
6
|
3
|
6
|
|
Third Washout Period
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Fourth Intervention Period
STARTED
|
4
|
6
|
3
|
6
|
|
Fourth Intervention Period
COMPLETED
|
4
|
6
|
3
|
6
|
|
Fourth Intervention Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Trazodone Contramid® OAD (Prototype 1) First
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase I; followed by 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase II; 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase III; and 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Trazodone Contramid® OAD (Prototype 2) First
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase I, followed by 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase II; 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase III; and 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Triticco® First
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase I; followed by 3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase II; 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase III; and 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
Desyrel® First
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in treatment phase I; followed by 1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in treatment phase II; 2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in treatment phase III; and 1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in treatment phase IV. There was a washout period of 7 days between treatment phases.
|
|---|---|---|---|---|
|
First Intervention Period
Adverse Event
|
0
|
0
|
1
|
0
|
|
First Washout Period
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Second Intervention Period
Adverse Event
|
0
|
0
|
1
|
0
|
|
Second Washout Period
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Third Washout Period
Adverse Event
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Comparative Bioavailability Study of Two Prototypes of Trazodone Controlled-release Products and Two Marketed Reference Products in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=24 Participants
Includes groups randomized to receive Trazodone Contramid® OAD (prototype 1) First, Trazodone Contramid® OAD (prototype 2) First, Triticco® First, and Desyrel® First.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
24.9 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.
AUC(0-t) = Area under the plasma concentration curve vs (versus) time data pairs, where t is the time of the last quantifiable concentration. Measured in nanogram x hours per milliliter (ng\*h/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Bioequivalence Based on AUC(0-t)
|
33883 ng*h/mL
Standard Deviation 8069
|
32445 ng*h/mL
Standard Deviation 8868
|
32928 ng*h/mL
Standard Deviation 8313
|
31841 ng*h/mL
Standard Deviation 7398
|
PRIMARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 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 (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Bioequivalence Based on AUC(0-∞)
|
35122 ng*h/mL
Standard Deviation 8655
|
33373 ng*h/mL
Standard Deviation 9299
|
34165 ng*h/mL
Standard Deviation 9105
|
32485 ng*h/mL
Standard Deviation 7621
|
PRIMARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 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 (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Bioequivalence Based on Cmax
|
1260 ng/mL
Standard Deviation 402
|
1475 ng/mL
Standard Deviation 489
|
1688 ng/mL
Standard Deviation 442
|
2081 ng/mL
Standard Deviation 492
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.
Apparent terminal half-life (t½.z) of trazodone in hours
Outcome measures
| Measure |
Trazodone Contramid® OAD (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Apparent Terminal Half-life (t½.z)
|
11.2 Hours
Standard Deviation 3.92
|
10.9 Hours
Standard Deviation 3.55
|
10.6 Hours
Standard Deviation 3.25
|
9.77 Hours
Standard Deviation 2.49
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.
Outcome measures
| Measure |
Trazodone Contramid® OAD (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Time to the Maximum Concentration (Tmax)
|
12.0 Hours
Interval 3.0 to 24.0
|
6.00 Hours
Interval 4.0 to 24.0
|
13.0 Hours
Interval 2.0 to 16.0
|
8.50 Hours
Interval 0.33 to 16.5
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.
Apparent First order terminal rate constant \[λz\] of trazodone in plasma expressed in 1/hours.
Outcome measures
| Measure |
Trazodone Contramid® OAD (Prototype 1)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=19 Participants
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=19 Participants
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=19 Participants
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Apparent First Order Terminal Rate Constant [λz]
|
0.07 1/hours
Standard Deviation 0.02
|
0.07 1/hours
Standard Deviation 0.02
|
0.07 1/hours
Standard Deviation 0.02
|
0.08 1/hours
Standard Deviation 0.02
|
Adverse Events
Trazodone Contramid® OAD (Prototype 1)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Trazodone Contramid® OAD (Prototype 2)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Triticco®
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Desyrel®
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Trazodone Contramid® OAD (Prototype 1)
n=21 participants at risk
1 \* 300 mg Trazodone Contramid® OAD (prototype 1) tablet test product dosed in either treatment phase.
|
Trazodone Contramid® OAD (Prototype 2)
n=20 participants at risk
1 \* 300 mg Trazodone Contramid® OAD (prototype 2) tablet test product dosed in either treatment phase.
|
Triticco®
n=23 participants at risk
2 \* 150 mg Triticco® tablets (at 07:30 and 19:30) reference product dosed in either treatment phase.
|
Desyrel®
n=21 participants at risk
3 \* 100 mg Desyrel® tablets (at 07:30, 15:30 and 23:30) reference product dosed in either treatment phase.
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/23
|
0.00%
0/21
|
|
Eye disorders
Eye pruritus
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
0.00%
0/23
|
4.8%
1/21 • Number of events 2
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/21
|
0.00%
0/20
|
4.3%
1/23 • Number of events 1
|
9.5%
2/21 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
4.8%
1/21 • Number of events 2
|
0.00%
0/20
|
4.3%
1/23 • Number of events 1
|
23.8%
5/21 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Fatigue
|
4.8%
1/21 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
17.4%
4/23 • Number of events 4
|
9.5%
2/21 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
19.0%
4/21 • Number of events 4
|
30.0%
6/20 • Number of events 6
|
26.1%
6/23 • Number of events 7
|
38.1%
8/21 • Number of events 9
|
|
Nervous system disorders
Headache
|
9.5%
2/21 • Number of events 3
|
5.0%
1/20 • Number of events 1
|
17.4%
4/23 • Number of events 5
|
28.6%
6/21 • Number of events 6
|
|
Nervous system disorders
Syncope
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
4.3%
1/23 • Number of events 1
|
0.00%
0/21
|
|
Nervous system disorders
Tremor
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/23
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
13.0%
3/23 • Number of events 3
|
4.8%
1/21 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.8%
1/21 • Number of events 1
|
0.00%
0/20
|
0.00%
0/23
|
0.00%
0/21
|
|
Nervous system disorders
Hypotensive shock
|
0.00%
0/21
|
0.00%
0/20
|
4.3%
1/23 • Number of events 1
|
0.00%
0/21
|
|
Vascular disorders
Hypotension
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Vascular disorders
Hypotension with convulsions
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia intercostal
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/21
|
0.00%
0/20
|
0.00%
0/23
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
2/21 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
0.00%
0/23
|
0.00%
0/21
|
Additional Information
Director of Regulatory Affairs
Labopharm Inc.
Phone: 1 450 686 1017
Results disclosure agreements
- Principal investigator is a sponsor employee The scientific results from this study are the property of the Sponsors, ie, Labopharm Inc., Canada and A.C.R.A.F. S.p.A., Italy. No data reported in the final integrated clinical trial report of this study will be used for publication in scientific journals and/or for presentation at scientific meetings without a previous agreed written consent between the Sponsors.
- Publication restrictions are in place
Restriction type: OTHER