HealthyPhase 1NCT03516630
Effects of Three Single Oral Doses of Trazodone on the QTc Interval Duration in Healthy Volunteers
A Phase 1 study testing Trazodone 20 mg, Trazodone 60 mg and Trazodone 140 mg in people with Healthy, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 1 site in Switzerland.
Trial summary
The present study has been designed to evaluate the effect of three doses of trazodone (20, 60 and 140 mg), in comparison to placebo, on the QT/QTc interval of healthy volunteers. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Trazodone 20 mg, Trazodone 60 mg and Trazodone 140 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Mar 2017to 1 May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Main Inclusion Criteria:
- Sex and Age: males/females, 20-50 years old inclusive
- Body mass index (BMI): 18.5-28 kg/m2 inclusive
- Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest (supine)
- Contraception and fertility (females only): females of child-bearing potential must be using at least one of the following reliable methods of contraception:
- Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
- A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
- A male sexual partner who agrees to use a male condom with spermicide
- A sterile sexual partner
Main Exclusion Criteria:
- ECG (12-leads, supine position): any of the following conditions: Heart rate <50 or >90 bpm; PR <120 or >200 msec; QRS >110 msec; QTcF males >430 msec, females >450 msec; Any qualitative/morphological abnormality except: sinus arrhythmia, isolated premature atrial complexes/premature ventricular complexes; T-wave/U-wave characteristics making determination of the end of the T-wave difficult such as biphasic T-waves, U-waves of width greater than 1/3 the width of the preceding T-wave
- Diseases: history of additional risk factors for torsade de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome); history of significant renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study
- Medications: any medications, including over the counter (OTC) medications and herbal products, and in particular medications that prolong the QT/QTc interval and potentially hepatotoxic drugs or hepatic/gastric enzyme inducers (i.e. phenobarbital, phenitoine, carbamazepine, chlorzoxazone and rifampicin) for 2 weeks before the start of the study and during the study duration. Hormonal contraceptives for females will be allowed
- Physical findings: clinically significant abnormal physical findings
- Laboratory analyses: clinically significant abnormal laboratory values
- Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study.
- Blood donation: blood donations for 3 months before this study
- Drug, alcohol, caffeine, tobacco: history of drug and/or alcohol dependence [alcohol abuse defined as >1 drink/day for females and >2 drinks/day for males, defined according to USDA Dietary Guidelines 2015-2020]; caffeine abuse (>5 cups coffee/tea/day) or tobacco abuse (more than 10 cigarettes/day)
- Drug test: positive result at the drug test at screening or day -1
- Alcohol test: positive alcohol breath test at day -1
- Grapefruit juice: grapefruit juice consumption within 2 weeks of the administration of the study treatments
- Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Centre, Single Dose, Randomised, Negative and Positive-controlled, Double-blind Trazodone vs. Negative Control (Placebo), Open-label vs. Positive Control (Moxifloxacin), 5-way Cross-over QT/QTc Study
The present study has been designed to evaluate the effect of three doses of trazodone (20, 60 and 140 mg), in comparison to placebo, on the QT/QTc interval of healthy volunteers. Trazodone oral drops 6% formulation has been selected in order to evaluate the three doses using the same formulation, because the lowest available strength for the tablet formulations is 50 mg. According to the E14 guideline on the evaluation of QT/QTc interval prolongation and proarrhythmic potential of antiarrhytmic drugs, a negative control (placebo) and a positive control (moxifloxacin) will also be assessed.
Read the detailed description
Twenty (20) healthy volunteers (about 50% males and 50% females) will be randomised.
Primary end-point:
- Evaluation of the relationship between the plasma concentration of trazodone (free base) and the change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia correction method (QTcF) method (∆∆QTcF).
- Trazodone can be declared to have no influence on QTc if the null hypothesis, that the upper bound of the two-sided 90% CI of the predicted mean placebo corrected change from baseline for QTcF is greater than 10 msec at the observed mean Cmax for the therapeutic dose of trazodone, can be rejected.
- Conditions
- Healthy
- Being tested
- Trazodone 20 mg, Trazodone 60 mg, Trazodone 140 mg, Placebo, Moxifloxacin 400mg
- Keywords
- Trazodone, QTc interval, Moxifloxacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trazodone 20 mgDrug
Oral drops
Trazodone 60 mgDrug
Oral drops
Trazodone 140 mgDrug
Oral drops
PlaceboDrug
Oral drops
Moxifloxacin 400mgDrug
Also called Avalox
Tablet
| Study group | Role | What they receive |
|---|---|---|
| TRZ 20 | Experimental | Product is administered as single dose in the morning, under fasting conditions. 10 drops for the dose of 20 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. Receives: Drug: Trazodone 20 mg |
| TRZ 60 | Experimental | Product is administered as single dose in the morning, under fasting conditions. 30 drops for the dose of 60 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. Receives: Drug: Trazodone 60 mg |
| TRZ 140 | Experimental | Product is administered as single dose in the morning, under fasting conditions. 70 drops for the dose of 140 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. Receives: Drug: Trazodone 140 mg |
| Placebo | Placebo comparator | Product is administered as single dose in the morning, under fasting conditions. Trazodone-matching placebo corresponding to 70 drops is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. Receives: Drug: Placebo |
| Moxifloxacin | Active comparator | Product is administered as single dose in the morning, under fasting conditions. One 400 mg tablet is swallowed (without chewing) with 240 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. Receives: Drug: Moxifloxacin 400mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relationship between trazodone plasma concentration and QTc
Evaluation of the relationship between the plasma concentration of trazodone (free base) and the change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia correction method (QTcF) method (∆∆QTcF).
Measured: pre-dose (-0.25 hours) and at 0.0833, 0.1666, 0.3333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Influence of trazodone on QTc
Trazodone can be declared to have no influence on QTc if the null hypothesis, that the upper bound of the two-sided 90% CI of the predicted mean placebo corrected change from baseline for QTcF is greater than 10 msec at the observed mean Cmax for the therapeutic dose of trazodone, can be rejected.
Measured: pre-dose (-0.25 hours) and at 0.0833, 0.1666, 0.3333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2018
- Study start20 Mar 2017
- Primary completion1 May 2017
- Study completion1 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aziende Chimiche Riunite Angelini Francesco S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A., eResearch Technology, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03516630
- Sponsor's protocol ID
- 039PO16364
- Other IDs
- CRO-PK-16-314
- Status last verified
- Jul 2020
- First submitted
- 24 Apr 2018
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tellone V, Rosignoli MT, Picollo R, Dragone P, Del Vecchio A, Comandini A, Radicioni M, Leuratti C, Calisti F. Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects. J Clin Pharmacol. 2020 Nov;60(11):1483-1495. doi: 10.1002/jcph.1640. Epub 2020 Jun 2.
PubMed 32488885
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Centre, Single Dose, Randomised, Negative and Positive-controlled, Double-blind Trazodone vs. Negative Control (Placebo), Open-label vs. Positive Control (Moxifloxacin), 5-way Cross-over QT/QTc Study
- ClinicalTrials.gov ID
- NCT03516630
- Acronym / sponsor ID
- 039PO16364
- Conditions
- Healthy
- Keywords
- Trazodone, QTc interval, Moxifloxacin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Aziende Chimiche Riunite Angelini Francesco S.p.AIndustry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A., eResearch Technology, Inc.
- Study start
- 20 Mar 2017 (actual)
- Primary completion
- 1 May 2017 (actual)
- Study completion
- 1 May 2017 (actual)
- First posted
- 4 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study has been designed to evaluate the effect of three doses of trazodone (20, 60 and 140 mg), in comparison to placebo, on the QT/QTc interval of healthy volunteers. Trazodone oral drops 6% formulation has been selected in order to evaluate the three doses using the same formulation, because the lowest available strength for the tablet formulations is 50 mg. According to the E14 guideline on the evaluation of QT/QTc interval prolongation and proarrhythmic potential of antiarrhytmic drugs, a negative control (placebo) and a positive control (moxifloxacin) will also be assessed.
Detailed description
Twenty (20) healthy volunteers (about 50% males and 50% females) will be randomised.
Primary end-point:
- Evaluation of the relationship between the plasma concentration of trazodone (free base) and the change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia correction method (QTcF) method (∆∆QTcF).
- Trazodone can be declared to have no influence on QTc if the null hypothesis, that the upper bound of the two-sided 90% CI of the predicted mean placebo corrected change from baseline for QTcF is greater than 10 msec at the observed mean Cmax for the therapeutic dose of trazodone, can be rejected.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| TRZ 20 | Experimental | Drug: Trazodone 20 mgProduct is administered as single dose in the morning, under fasting conditions. 10 drops for the dose of 20 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. |
| TRZ 60 | Experimental | Drug: Trazodone 60 mgProduct is administered as single dose in the morning, under fasting conditions. 30 drops for the dose of 60 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. |
| TRZ 140 | Experimental | Drug: Trazodone 140 mgProduct is administered as single dose in the morning, under fasting conditions. 70 drops for the dose of 140 mg is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. |
| Placebo | Placebo comparator | Drug: PlaceboProduct is administered as single dose in the morning, under fasting conditions. Trazodone-matching placebo corresponding to 70 drops is suspended in 120 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. |
| Moxifloxacin | Active comparator | Drug: Moxifloxacin 400mgProduct is administered as single dose in the morning, under fasting conditions. One 400 mg tablet is swallowed (without chewing) with 240 mL of still mineral water. A wash-out interval of at least 7 days is required before the administration of the other doses foreseen in the study. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
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 20 mgOral drops | Drug | TRZ 20 |
| Trazodone 60 mgOral drops | Drug | TRZ 60 |
| Trazodone 140 mgOral drops | Drug | TRZ 140 |
| PlaceboOral drops | Drug | Placebo |
| Moxifloxacin 400mgAlso: AvaloxTablet | Drug | Moxifloxacin |
Primary outcome
Relationship between trazodone plasma concentration and QTc
Time frame: pre-dose (-0.25 hours) and at 0.0833, 0.1666, 0.3333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Evaluation of the relationship between the plasma concentration of trazodone (free base) and the change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia correction method (QTcF) method (∆∆QTcF).
Influence of trazodone on QTc
Time frame: pre-dose (-0.25 hours) and at 0.0833, 0.1666, 0.3333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Trazodone can be declared to have no influence on QTc if the null hypothesis, that the upper bound of the two-sided 90% CI of the predicted mean placebo corrected change from baseline for QTcF is greater than 10 msec at the observed mean Cmax for the therapeutic dose of trazodone, can be rejected.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Derived from this study: PubMed 32488885Tellone V, Rosignoli MT, Picollo R, Dragone P, Del Vecchio A, Comandini A, Radicioni M, Leuratti C, Calisti F. Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects. J Clin Pharmacol. 2020 Nov;60(11):1483-1495. doi: 10.1002/jcph.1640. Epub 2020 Jun 2.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trazodone 20 mg, Trazodone 60 mg and Trazodone 140 mg in people with Healthy, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Relationship between trazodone plasma concentration and QTc (time frame: pre-dose (-0.25 hours) and at 0.0833, 0.1666, 0.3333, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.). The study lists 2 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 NCT03516630, which also lists 1 linked publication.
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 31 Jul 2020.