A Study to Compare the Bioavailability of 300 mg Trazodon... | NCT01121900

NCT01121900

Status Module

Sponsor/Collaborators Module

Oversight Module

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No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Trazodone HCl OAD	Experimental	OAD: Once A Day	Drug: Trazodone HCl
Trazodone HCl (Apotex Corp.)	Active Comparator		Drug: Trazodone HCl

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Trazodone HCl	Drug	Dosage form: Extended-release caplets containing 300 mg trazodone HCl Dose: 300 mg trazodone HCl extended-release caplets (one caplet) at 23:30 on Day 1 of the test product treatment period following a fasting period of at least 4 hours.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Bioequivalence Based Cmax	Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).	68 hours
Bioequivalence Based on AUC(0-tlast)	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).	68 hours
Bioequivalence Based on AUC(0-∞)	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).	68 hours

Measure	Description	Time Frame
Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]		24 hours
Time to Maximum Plasma Concentration (Tmax)		68 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy male and female subjects 18 to < 56 years of age.
Body mass within 10% of the ideal mass in relation to height and age, according to Body Mass Index.
Body mass not less than 53 kg.
Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the laboratory reference ranges for the relevant laboratory tests (unless the investigator considered the deviation to be irrelevant for the purpose of the study).
Normal 12-lead electrocardiogram (ECG) and vital signs, or abnormalities, which the investigator did not consider a disqualification for participation in the study.
Willingness to undergo a pre- and post-study physical examination and laboratory investigations.
Ability to comprehend and willingness to sign both statements of informed consent (for screening and period-related procedures).
Non-smoker or past smoker who stopped the use of any form of tobacco, including snuff or similar products, at least 3 months before entering the study.
For females, the following conditions had to be met:
1. Had been surgically sterilized or undergone a hysterectomy, or
2. Was of childbearing potential, and all of the following conditions were met:
  1. Had a negative pregnancy test at screening. If this test was positive, the subject was to be excluded from the study before receiving study medication. In the rare circumstance that a pregnancy was discovered after the subjects received the study medication, every attempt was to be made to follow such subjects to term.
  2. Had to agree to use an accepted method of contraception (i.e., spermicide and barrier methods or spermicide and non-hormonal intrauterine contraceptive device). The subject had to agree to continue with the same method throughout the study. Hormonal contraceptives were not allowed.
3. Females not of childbearing potential could also have been included if they had no menstrual period for one year and were considered as post-menopausal.

Exclusion Criteria:

Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to have limited the validity of consent to participate in the study or to have limited the ability to comply with protocol requirements.
History of, or current compulsive alcohol abuse (> 10 drinks weekly), or regular exposure to other substances of abuse.
Use of any medication, prescribed or over-the-counter, within 2 weeks prior to the first administration of study medication except if this would not have affected the outcome of the study in the opinion of the investigator. Hormonal contraceptive agents were not allowed.
Participation in another study with an experimental drug, where the last administration (of previous study medication) was within 8 weeks before the first administration of study medication.
Treatment within the previous 3 months with any drug with a well-defined potential for adversely affecting a major organ or system.
A major illness during the 3 months before commencement of the screening period.
History of hypersensitivity to the study medication or any related medication.
History of bronchial asthma.
History of epilepsy.
History of porphyria.
Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to have influenced the study outcome.
Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of study medication.
Diagnosis of hypotension made during the screening period.
Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
Resting pulse of > 100 beats per minute or < 40 beats per minute during the screening period, either supine or standing.
Positive testing for HIV and/or Hepatitis B and/or Hepatitis C.
Positive urine screen for drugs of abuse.
Positive urine screen for tobacco use.
A serum pregnancy test (beta human chorionic gonadotropin [β-HCG]) either positive or not performed or lactation.

Contacts/Locations Module

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References Module

Label	URL
Approved Labelling	View source

IPD Sharing Statement Module

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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

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No data is available for this block.

Document Section

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Derived Section

Miscellaneous Info Module

Submission Tracking

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No data is available for this block.

Condition Browse Module

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No data is available for this block.

Intervention Browse Module

Masking Info

FG00013 subjects
FG00113 subjects

Type of Units Analyzed

ID	Title	Description
BG000	Entire Study Population	Includes groups randomized to receive Test first and Reference first.

Units	Counts
Participants	BG00026

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG00026
>=65 years	BG000

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00025.2± 10.88

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00016
Male	BG00010

Region of Enrollment

Number

participants

Title

Denominators

Categories

South Africa

Title	Measurements
	BG00026

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Bioequivalence Based Cmax

Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

ng/mL

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts
Participants	OG00023 OG00123

Title

Denominators

Categories

Title	Measurements
	OG0001230.7± 499.1 OG0012947.7± 734.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Mean ratio	39.8			2-Sided	90	34.4	46.0			Test/reference (%)	Yes	Non-Inferiority or Equivalence	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 is between 80% and 125%.

Primary

Bioequivalence Based on AUC(0-tlast)

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).

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

hr*ng/mL

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts

Primary

Bioequivalence Based on AUC(0-∞)

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).

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

h*ng/mL

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts
Participants

Secondary

Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

h*ng/mL

24 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts
Participants

Secondary

Time to Maximum Plasma Concentration (Tmax)

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Median

Full Range

Hours

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts
Participants	OG000

Secondary

Apparent Terminal Elimination Rate Constant (λz)

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.

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

1/hour

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts

Secondary

Apparent Terminal Half-life (t½.z)

The elimination half-life (T½z) of trazodone in plasma (time it takes for the concentration of trazodone to fall to half), expressed in hours.

The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

Posted

Mean

Standard Deviation

Hours

68 hours

ID	Title	Description
OG000	Trazodone Contramid® OAD	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.
OG001	Trazodone IR (Apotex Corp.)	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.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Trazodone Contramid® OAD	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.			0	24	7	24
EG001	Trazodone IR (Apotex Corp.)	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.			0	25	8	25

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dizziness	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0006 events5 affected24 at risk EG0015 events4 affected25 at risk
Headache	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0013 events3 affected25 at risk
Nausea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0006 events4 affected24 at risk EG0012 events2 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk
Oedema peripheral	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk

ID	Term
D014196	Trazodone

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011728	Pyridones
D011725	Pyridines