HealthyPhase 1NCT01121913

Comparative Bioavailability Study of Two Prototypes of Trazodone Controlled-release Products and Two Marketed Reference Products in Healthy Volunteers

A Phase 1 study testing Trazodone HCl in people with Healthy, run by Labopharm Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The objectives of this study were: to compare the pharmacokinetic profiles of two prototype controlled-release (CR) trazodone hydrochloride (HCl) 300 mg tablets versus two reference products: Trittico® AC (2 x 150 mg CR tablets) and Desyrel® (3 x 100 mg IR (immediate-release) tablets) under fasting condition; to… Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Trazodone HCl
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: No sites listed yet
Study dates: Mar 2005to Apr 2005
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male and female subjects 18 to 45 years of age (inclusive).
Body mass within 10% of the ideal mass in relation to height and age, according to the BMI.
Body mass not less than 70 kg. The normal total circulating blood volume in males and in females is about 71 mL/kg and 65 mL/kg of the body mass, respectively (Meyer, 1988). No subject will have more than 13% of estimated blood volume taken during the study (Standards for the Practice of Blood Transfusion in South Africa, 1999).
Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the "normal ranges" for the relevant laboratory tests (unless the clinical investigator considers the deviation to be irrelevant for the purpose of the study).
Normal ECG and vital signs, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study.
Willingness to undergo pre- and post-study physical examinations, and pre- and post study laboratory investigations.

Show all 14Show fewer

Ability to comprehend and willingness to sign both statements of informed consent (for screening and phase-related procedures).
Non-smoker or past smoker who stopped smoking at least 3 months before entering the study.
For females, the following conditions are to be met:
has been surgically sterilized, or
is of childbearing potential, and all of the following conditions are met:
had a normal menstrual flow within 1 month before study entry, and
has a negative urine pregnancy test at screening. If this test is positive, the subject will be excluded from the study before receiving study medication. In the rare circumstance that a pregnancy is discovered after the subjects received the study drug, every attempt must be made to follow such subjects to term, and
must agree to use an accepted method of contraception (i.e., spermicide and barrier methods or spermicide and intrauterine contraceptive device). The subject must agree to continue with the same method throughout the study. Hormonal contraceptives will be allowed, with a stable dose for at least one month prior to the first intake of study medication.

Who cannot join

Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit 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 will not affect the outcome of the study in the opinion of the clinical investigator. Use of hormonal contraceptive agents by females is allowed.
Participation in another study with an experimental drug 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 with evidence to this effect.
A major illness during the 3 months before commencement of the screening period.

Show all 20Show fewer

History of hypersensitivity to the study drug or any related drugs.
History of bronchial asthma.
History of epilepsy.
Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence 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 rate of > 100 beats per minute or < 45 beats per minute during the screening period, either supine or standing.
Positive testing for HIV, hepatitis B surface antigen and/or Hepatitis C antibodies.
Positive urine screen for drugs of abuse.
A urine pregnancy test (ß-HCG) either positive or not performed or lactation.
Positive urine screen for tobacco use (SureStepTM Smoke Check Tests and One-Step Cotinine (COT) Tests).
History of marijuana, barbiturate, amphetamine or narcotic abuse within 12 months prior to study start.
Significant liver disease, defined as active hepatitis or elevated liver enzymes (e.g. aspartate aminotransferase, alanine aminotransferase) >2 times the upper boundary of the normal range.

About this study

Official title: A Randomized, Four-way Crossover Pilot Study to Compare the Relative Bioavailability of Two Prototype Once-a-day Trazodone Hydrochloride Products and Two Marketed Reference Products Following an Equivalent Daily Dose Administration Under Fasting Conditions in Healthy Volunteers

The objectives of this study were:

to compare the pharmacokinetic profiles of two prototype controlled-release (CR) trazodone hydrochloride (HCl) 300 mg tablets versus two reference products: Trittico® AC (2 x 150 mg CR tablets) and Desyrel® (3 x 100 mg IR (immediate-release) tablets) under fasting condition;
to assess the controlled release properties of the two prototype formulations;
to select a prototype formulation for further development;
to validate the blood sampling schedule for future pivotal pharmacokinetic studies;
to determine the appropriate sample size for pivotal studies based in the intra-subject variability.

Conditions: Healthy
Being tested: Trazodone HCl
Keywords: Healthy subjects

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Trazodone HClDrug
The dosage of trazodone.HCl during this treatment phase was a single oral dose of 300 mg (one CR tablet) at 07:30 (after an overnight fast of at least 10 hours) on clinic days.
Trazodone HClDrug
Also called Oleptro
The dosage of trazodone.HCl during this treatment phase was a single oral dose of 300 mg (one CR tablet) at 07:30 (after an overnight fast of at least 10 hours) on clinic days.
Trazodone HClDrug
The dosage of trazodone.HCl during this treatment phase was 2 oral doses of 150 mg each: one controlled-release (CR) tablet at 07:30 (after an overnight fast of at least 10 hours) and 19:30 (after a fast of at least 2 hours) on clinic days.
Trazodone HClDrug
The dosage of trazodone.HCl during this treatment phase was three oral doses of 100 mg each: one immediate-release (IR) tablet at 07:30 (after an overnight fast of at least 10 hours), 15:30 and 23:30 (both dosages after a fast of at least 2 hours) on clinic days.

Study groups in NCT01121913
Study group	Role	What they receive
Trazodone Contramid® OAD (test product 1)	Experimental	Test product 1 and Test product 2 are two different prototype formulations of Trazodone Contramid® OAD (once a day) Receives: Drug: Trazodone HCl
Trazodone Contramid® OAD(test product 2)	Experimental	Test product 1 and Test product 2 are two different prototype formulations of Trazodone Contramid® OAD (once a day) Receives: Drug: Trazodone HCl
Triticco®	Active comparator	Not described Receives: Drug: Trazodone HCl
Desyrel®	Active comparator	Not described Receives: Drug: Trazodone HCl

What is being measured

The primary outcome is the main question the study is designed to answer.

Bioequivalence Based on AUC(0-t)
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).
Measured: 72 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).
Measured: 72 hours
Bioequivalence Based on Cmax
Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).
Measured: 72 hours

Secondary outcomes (3)

Apparent Terminal Half-life (t½.z)
Apparent terminal half-life (t½.z) of trazodone in hours
Measured: 72 hours
Time to the Maximum Concentration (Tmax)
Measured: 72 hours
Apparent First Order Terminal Rate Constant [λz]
Apparent First order terminal rate constant [λz] of trazodone in plasma expressed in 1/hours.
Measured: 72 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2005Apr 2005

First posted12 May 2010 (estimated)
Study startMar 2005
Primary completionApr 2005

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01121913
Sponsor's protocol ID: 04ACL101
Status last verified: Apr 2012
First submitted: 10 May 2010
Last updated: 27 Apr 2012
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Active, not recruitingPhase 3
A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 With Influenza Vaccine in Adults ≥ 50 Years of Age
Pneumococcal Disease
Recruiting
Effect of a Fermented Dairy Protein With Prebiotic Fiber on GI Complaints
Digestive Health, Quality of Life
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Four-way Crossover Pilot Study to Compare the Relative Bioavailability of Two Prototype Once-a-day Trazodone Hydrochloride Products and Two Marketed Reference Products Following an Equivalent Daily Dose Administration Under Fasting Conditions in Healthy Volunteers
ClinicalTrials.gov ID: NCT01121913
Acronym / sponsor ID: 04ACL101
Conditions: Healthy
Keywords: Healthy subjects
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Labopharm Inc.Industry (pharma, biotech, devices)
Study start: Mar 2005
Primary completion: Apr 2005 (actual)
First posted: 12 May 2010 (estimated)
Results: Posted 16 Aug 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The objectives of this study were:

to compare the pharmacokinetic profiles of two prototype controlled-release (CR) trazodone hydrochloride (HCl) 300 mg tablets versus two reference products: Trittico® AC (2 x 150 mg CR tablets) and Desyrel® (3 x 100 mg IR (immediate-release) tablets) under fasting condition;
to assess the controlled release properties of the two prototype formulations;
to select a prototype formulation for further development;
to validate the blood sampling schedule for future pivotal pharmacokinetic studies;
to determine the appropriate sample size for pivotal studies based in the intra-subject variability.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Trazodone Contramid® OAD (test product 1)	Experimental	Drug: Trazodone HClTest product 1 and Test product 2 are two different prototype formulations of Trazodone Contramid® OAD (once a day)
Trazodone Contramid® OAD(test product 2)	Experimental	Drug: Trazodone HClTest product 1 and Test product 2 are two different prototype formulations of Trazodone Contramid® OAD (once a day)
Triticco®	Active comparator	Drug: Trazodone HCl
Desyrel®	Active comparator	Drug: Trazodone HCl

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

Healthy male and female subjects 18 to 45 years of age (inclusive).
Body mass within 10% of the ideal mass in relation to height and age, according to the BMI.
Body mass not less than 70 kg. The normal total circulating blood volume in males and in females is about 71 mL/kg and 65 mL/kg of the body mass, respectively (Meyer, 1988). No subject will have more than 13% of estimated blood volume taken during the study (Standards for the Practice of Blood Transfusion in South Africa, 1999).
Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the "normal ranges" for the relevant laboratory tests (unless the clinical investigator considers the deviation to be irrelevant for the purpose of the study).
Normal ECG and vital signs, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study.

Key exclusion criteria (20 listed)

Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit 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 will not affect the outcome of the study in the opinion of the clinical investigator. Use of hormonal contraceptive agents by females is allowed.
Participation in another study with an experimental drug 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 with evidence to this effect.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trazodone HClThe dosage of trazodone.HCl during this treatment phase was a single oral dose of 300 mg (one CR tablet) at 07:30 (after an overnight fast of at least 10 hours) on clinic days.	Drug	Trazodone Contramid® OAD (test product 1)
Trazodone HClAlso: OleptroThe dosage of trazodone.HCl during this treatment phase was a single oral dose of 300 mg (one CR tablet) at 07:30 (after an overnight fast of at least 10 hours) on clinic days.	Drug	Trazodone Contramid® OAD(test product 2)
Trazodone HClThe dosage of trazodone.HCl during this treatment phase was 2 oral doses of 150 mg each: one controlled-release (CR) tablet at 07:30 (after an overnight fast of at least 10 hours) and 19:30 (after a fast of at least 2 hours) on clinic days.	Drug	Triticco®
Trazodone HClThe dosage of trazodone.HCl during this treatment phase was three oral doses of 100 mg each: one immediate-release (IR) tablet at 07:30 (after an overnight fast of at least 10 hours), 15:30 and 23:30 (both dosages after a fast of at least 2 hours) on clinic days.	Drug	Desyrel®

Primary outcome

Bioequivalence Based on AUC(0-t)
Time frame: 72 hours
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).
Bioequivalence Based on AUC(0-∞)
Time frame: 72 hours
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).
Bioequivalence Based on Cmax
Time frame: 72 hours
Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).

3 secondary outcomes

Apparent Terminal Half-life (t½.z)
Time frame: 72 hours
Time to the Maximum Concentration (Tmax)
Time frame: 72 hours
Apparent First Order Terminal Rate Constant [λz]
Time frame: 72 hours

Results and safety

Results posted to the registry on 16 Aug 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Trazodone Contramid® OAD (Prototype 1) First	6	6
Trazodone Contramid® OAD (Prototype 2) First	6	6
Triticco® First	6	5
Desyrel® First	6	6

Primary outcome: Bioequivalence Based on AUC(0-t)

Time frame: 72 hours. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Trazodone Contramid® OAD (Prototype 1) n = 19	Trazodone Contramid® OAD (Prototype 2) n = 19	Triticco® n = 19	Desyrel® n = 19
Value	33883 (8069)	32445 (8868)	32928 (8313)	31841 (7398)

Trazodone Contramid® OAD (Prototype 1) vs Triticco®: Mean ratio: 102 (90% CI 91.8 to 114)
Trazodone Contramid® OAD (Prototype 1) vs Desyrel®: Mean ratio: 105 (90% CI 93.9 to 117)
Trazodone Contramid® OAD (Prototype 2) vs Triticco®: Mean ratio: 95.3 (90% CI 85.5 to 106)

Population analysed: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.

Primary outcome: Bioequivalence Based on AUC(0-∞)

Time frame: 72 hours. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Trazodone Contramid® OAD (Prototype 1) n = 19	Trazodone Contramid® OAD (Prototype 2) n = 19	Triticco® n = 19	Desyrel® n = 19
Value	35122 (8655)	33373 (9299)	34165 (9105)	32485 (7621)

Trazodone Contramid® OAD (Prototype 1) vs Triticco®: Mean ratio: 102 (90% CI 91.8 to 114)
Trazodone Contramid® OAD (Prototype 1) vs Desyrel®: Mean ratio: 106 (90% CI 95.1 to 118)
Trazodone Contramid® OAD (Prototype 2) vs Triticco®: Mean ratio: 94.9 (90% CI 85.1 to 106)

Population analysed: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.

Primary outcome: Bioequivalence Based on Cmax

Time frame: 72 hours. Mean (Standard Deviation). Unit: ng/mL

Measure	Trazodone Contramid® OAD (Prototype 1) n = 19	Trazodone Contramid® OAD (Prototype 2) n = 19	Triticco® n = 19	Desyrel® n = 19
Value	1260 (402)	1475 (489)	1688 (442)	2081 (492)

Trazodone Contramid® OAD (Prototype 1) vs Triticco®: Mean ratio: 73.3 (90% CI 63.2 to 85)
Trazodone Contramid® OAD (Prototype 1) vs Desyrel®: Mean ratio: 59.8 (90% CI 51.5 to 69.4)
Trazodone Contramid® OAD (Prototype 2) vs Triticco®: Mean ratio: 83 (90% CI 71.5 to 96.4)

Population analysed: The dataset for pharmacokinetic analysis comprised the 19 subjects who completed the study as per protocol.

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Trazodone Contramid® OAD (Prototype 1)	0 of 21 (0%)	7 of 21 (33.3%)	Not reported
Trazodone Contramid® OAD (Prototype 2)	0 of 20 (0%)	9 of 20 (45%)	Not reported
Triticco®	0 of 23 (0%)	14 of 23 (60.9%)	Not reported
Desyrel®	0 of 21 (0%)	14 of 21 (66.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Approved labellingLink provided by the sponsor.

Related trials for Healthy

RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Active, not recruitingPhase 3
A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 With Influenza Vaccine in Adults ≥ 50 Years of Age
Pneumococcal Disease
Recruiting
Effect of a Fermented Dairy Protein With Prebiotic Fiber on GI Complaints
Digestive Health, Quality of Life
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trazodone HCl in people with Healthy, run by Labopharm Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bioequivalence Based on AUC(0-t) (time frame: 72 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01121913.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2012.