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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01121926
Recruitment Status : Completed
First Posted : May 12, 2010
Results First Posted : August 16, 2010
Last Update Posted : April 30, 2012
Sponsor:
Information provided by (Responsible Party):
Labopharm Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Healthy Subjects
Bioavailability
Pharmacokinetics
Intervention Drug: Trazodone HCl
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Test (Trazodone Contramid® OAD) First Reference (Trazodone IR [Apotex Corp.]) First
Hide Arm/Group Description

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.

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.

Period Title: First Intervention Period
Started 15 15
Completed 14 15
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Period Title: Washout Period
Started 14 15
Completed 14 13
Not Completed 0 2
Reason Not Completed
Adverse Event             0             1
Positive pregnancy test             0             1
Period Title: Second Intervention Period
Started 14 13
Completed 14 13
Not Completed 0 0
Arm/Group Title Entire Study Population
Hide Arm/Group Description

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

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years
0
   0.0%
Between 18 and 65 years
30
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
25.7  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
9
  30.0%
Male
21
  70.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 30 participants
30
1.Primary Outcome
Title Bioequivalence Based on Cmax,ss
Hide Description Cmax,ss = Maximum plasma concentration (Cmax) at steady state (ss): (Cmax,ss). Measured in nanograms per milliliter (ng/mL).
Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: ng/mL
1812.026  (620.625) 3117.778  (757.508)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trazodone Contramid® OAD, Trazodone HCl (Apotex Corp.)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence is established when the ratio of geometric Least Squares means (LSmeans) and confidence interval calculated from the exponential of the difference between the Test and Reference product for the ln-transformed parameter Cmax,ss is between 80% and 125%.
Method of Estimation Estimation Parameter Mean ratio
Estimated Value 56.53
Confidence Interval (2-Sided) 90%
49.99 to 63.94
Estimation Comments Test/reference (%)
2.Primary Outcome
Title Bioequivalence Based on AUCss
Hide Description

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).

Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
29131.374  (9930.767) 33058.024  (8006.118)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trazodone Contramid® OAD, Trazodone HCl (Apotex Corp.)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence is established when the ratio of geometric Least Squares means (LSmeans) and confidence interval calculated from the exponential of the difference between the Test and Reference product for the ln-transformed parameter AUCss is between 80% and 125%.
Method of Estimation Estimation Parameter Mean ratio
Estimated Value 85.72
Confidence Interval (2-Sided) 90%
81.05 to 90.67
Estimation Comments Test/reference (%)
3.Secondary Outcome
Title Minimum Plasma Concentration (Cmin,ss)
Hide Description Minimum plasma concentration at steady state (Cmin,ss). Measured in nanograms per milliliter (ng/mL)
Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: ng/mL
673.889  (354.647) 842.763  (273.592)
4.Secondary Outcome
Title Plasma Concentration at 24 Hours Post-evening Dose (C24h)
Hide Description Plasma concentration at 24 hours post-evening dose (C24h) in nanograms per milliliter (ng/mL)
Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: ng/mL
747.270  (329.025) 919.111  (289.382)
5.Secondary Outcome
Title Time to Peak Exposure (Tmax)
Hide Description Time to peak exposure (Tmax) at steady state.
Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Median (Full Range)
Unit of Measure: hours
8.00
(3.00 to 16.0)
8.33
(8.33 to 19.0)
6.Secondary Outcome
Title Percentage Swing
Hide Description

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.

Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Percentage swing
210.769  (127.806) 302.805  (144.467)
7.Secondary Outcome
Title Percentage Peak-Trough Fluctuation (%PTF)
Hide Description

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

Time Frame 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetic analysis comprised the 27 subjects who completed the study as per protocol.
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description:
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.) 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.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Percentage Peak-Trough Fluctuation
97.090  (28.357) 174.768  (69.648)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Hide Arm/Group Description 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.) 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.
All-Cause Mortality
Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/28 (0.00%)      0/29 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trazodone Contramid® OAD Trazodone HCl (Apotex Corp.)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/28 (39.29%)      13/29 (44.83%)    
Gastrointestinal disorders     
Nausea * 1  2/28 (7.14%)  2 2/29 (6.90%)  2
Constipation * 1  2/28 (7.14%)  2 1/29 (3.45%)  1
Dry mouth * 1  3/28 (10.71%)  3 1/29 (3.45%)  1
Nervous system disorders     
Headache * 1  5/28 (17.86%)  5 3/29 (10.34%)  3
Dizziness * 1  2/28 (7.14%)  3 4/29 (13.79%)  4
Psychiatric disorders     
Insomnia * 1  0/28 (0.00%)  0 2/29 (6.90%)  2
Respiratory, thoracic and mediastinal disorders     
Nasal congestion * 1  4/28 (14.29%)  4 1/29 (3.45%)  1
Dyspnoea * 1  0/28 (0.00%)  0 2/29 (6.90%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Regulatory Affairs
Organization: Labopharm Inc.
Phone: 1 450 686 1017
Layout table for additonal information
Responsible Party: Labopharm Inc.
ClinicalTrials.gov Identifier: NCT01121926    
Other Study ID Numbers: 04ACL108
First Submitted: May 10, 2010
First Posted: May 12, 2010
Results First Submitted: June 22, 2010
Results First Posted: August 16, 2010
Last Update Posted: April 30, 2012