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 at Steady State (NCT NCT01121926)
NCT ID: NCT01121926
Last Updated: 2012-04-30
Results Overview
Cmax,ss = Maximum plasma concentration (Cmax) at steady state (ss): (Cmax,ss). Measured in nanograms per milliliter (ng/mL).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
9 days
Results posted on
2012-04-30
Participant Flow
Participant milestones
| Measure |
Test (Trazodone Contramid® OAD) First
Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet administered once daily) dosed in first treatment phase followed by Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in the second treatment phase. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
IR = Immediate Release.
|
Reference (Trazodone IR [Apotex Corp.]) First
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in first treatment phase followed by Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet administered once daily) dosed in the second treatment phase. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
IR = Immediate Release.
|
|---|---|---|
|
First Intervention Period
STARTED
|
15
|
15
|
|
First Intervention Period
COMPLETED
|
14
|
15
|
|
First Intervention Period
NOT COMPLETED
|
1
|
0
|
|
Washout Period
STARTED
|
14
|
15
|
|
Washout Period
COMPLETED
|
14
|
13
|
|
Washout Period
NOT COMPLETED
|
0
|
2
|
|
Second Intervention Period
STARTED
|
14
|
13
|
|
Second Intervention Period
COMPLETED
|
14
|
13
|
|
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 administered once daily) dosed in first treatment phase followed by Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in the second treatment phase. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
IR = Immediate Release.
|
Reference (Trazodone IR [Apotex Corp.]) First
Trazodone IR (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in first treatment phase followed by Trazodone Contramid® OAD (Once-A-Day) test product (300 mg tablet administered once daily) dosed in the second treatment phase. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
IR = Immediate Release.
|
|---|---|---|
|
First Intervention Period
Adverse Event
|
1
|
0
|
|
Washout Period
Adverse Event
|
0
|
1
|
|
Washout Period
Positive pregnancy test
|
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 at Steady State
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=30 Participants
Includes groups randomized to receive Trazodone Contramid® OAD (Once-A-Day) test product first and Trazodone IR (Apotex Corp.) reference product first.
IR = Immediate Release
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
25.7 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Cmax,ss = Maximum plasma concentration (Cmax) at steady state (ss): (Cmax,ss). Measured in nanograms per milliliter (ng/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 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 Cmax,ss
|
1812.026 ng/mL
Standard Deviation 620.625
|
3117.778 ng/mL
Standard Deviation 757.508
|
PRIMARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
AUCss = Area under the plasma concentration curve (AUC) vs. time data pairs at steady state (ss): AUCss. Measured in nanograms x hours per milliliter (ng\*h/mL).
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 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 AUCss
|
29131.374 ng*h/mL
Standard Deviation 9930.767
|
33058.024 ng*h/mL
Standard Deviation 8006.118
|
SECONDARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Minimum plasma concentration at steady state (Cmin,ss). Measured in nanograms per milliliter (ng/mL)
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Minimum Plasma Concentration (Cmin,ss)
|
673.889 ng/mL
Standard Deviation 354.647
|
842.763 ng/mL
Standard Deviation 273.592
|
SECONDARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Plasma concentration at 24 hours post-evening dose (C24h) in nanograms per milliliter (ng/mL)
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Plasma Concentration at 24 Hours Post-evening Dose (C24h)
|
747.270 ng/mL
Standard Deviation 329.025
|
919.111 ng/mL
Standard Deviation 289.382
|
SECONDARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Time to peak exposure (Tmax) at steady state.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Time to Peak Exposure (Tmax)
|
8.00 hours
Interval 3.0 to 16.0
|
8.33 hours
Interval 8.33 to 19.0
|
SECONDARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Percentage swing is a pharmacokinetic parameter calculated as follows: ((Cmax,ss - Cmin,ss)/Cmin,ss)\*100. Where: Cmax,ss = Maximum concentration at steady state; Cmin,ss = Minimum concentration at steady state. It was calculated over 24 hours on day 9.
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Percentage Swing
|
210.769 Percentage swing
Standard Deviation 127.806
|
302.805 Percentage swing
Standard Deviation 144.467
|
SECONDARY outcome
Timeframe: 9 daysPopulation: The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Percentage Peak-Trough Fluctuation (%PTF) of trazodone calculated as \[100\*(Cmax-Cmin)/Cav\]. Cmax: Maximum plasma concentration Cmin: Minimum plasma concentration Cav: Average plasma concentration
Outcome measures
| Measure |
Trazodone Contramid® OAD
n=27 Participants
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=27 Participants
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
|---|---|---|
|
Percentage Peak-Trough Fluctuation (%PTF)
|
97.090 Percentage Peak-Trough Fluctuation
Standard Deviation 28.357
|
174.768 Percentage Peak-Trough Fluctuation
Standard Deviation 69.648
|
Adverse Events
Trazodone Contramid® OAD
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Trazodone HCl (Apotex Corp.)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Trazodone Contramid® OAD
n=28 participants at risk
Trazodone Contramid® OAD test product (300 mg tablet administered once daily) dosed in either period. A drug-free period of 7 calendar days separated the last administration of study medication in Phase 1 and the first administration of study medication in Phase 2.
|
Trazodone HCl (Apotex Corp.)
n=29 participants at risk
Trazodone HCl (Apotex Corp.) reference product (100 mg tablet administered thrice daily) dosed in either period. A drug-free period of 7 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
Headache
|
17.9%
5/28 • Number of events 5
|
10.3%
3/29 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
7.1%
2/28 • Number of events 3
|
13.8%
4/29 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.3%
4/28 • Number of events 4
|
3.4%
1/29 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/28
|
6.9%
2/29 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
7.1%
2/28 • Number of events 2
|
6.9%
2/29 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
7.1%
2/28 • Number of events 2
|
3.4%
1/29 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
10.7%
3/28 • Number of events 3
|
3.4%
1/29 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/28
|
6.9%
2/29 • 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. 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