Study to Evaluate the Effects of Tramadol Hydrochloride on Cardiac Repolarization in Healthy Participants

August 27, 2018 updated by: Janssen Scientific Affairs, LLC

A Randomized, Double-Blind, Placebo- and Positive-Controlled, Multiple Dose, Four Way Crossover Study to Evaluate the Effects of Tramadol Hydrochloride on Cardiac Repolarization in Healthy Subjects at Therapeutic and Supratherapeutic Dose Levels

The purpose of this study is to assess the effects of multiple doses of an immediate release (IR) formulation of tramadol hydrochloride (HCl) at therapeutic and supratherapeutic levels in healthy adult participants on the electrocardiogram (ECG) QT interval corrected for heart rate (QTc).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized (study medication assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), 4-way crossover (method used to switch participants from one treatment arm to another), placebo- and positive-controlled (the experimental treatment or procedure is compared to an inactive substance and a standard treatment or procedure), single site, multiple dose study. The study has 3 phases: a Screening Phase (up to 35 days); a Double-blind Treatment Phase (4 treatment periods with a washout period of 7 to 15 days); and a Post-treatment Phase (Day 5 of Period 4 or at the time of early withdrawal). All eligible participants will receive each of the 4 treatments: tramadol HCl at therapeutic dose of 400 milligram per day (mg/day), tramadol HCl at supratherapeutic dose of 600 mg/day, placebo, and positive control moxifloxacin 400 mg; in any of the treatment period as per assigned treatment sequence. The total duration of each participant's participation will be up to a maximum of 100 days. Participants' safety will be monitored throughout the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Woman participant of child-bearing potential, must have a negative serum beta-human chorionic gonadotropin pregnancy test at Screening; and a negative urine pregnancy test on Day 1 of each treatment period
  • Standard electroencephalogram (EEG) that is normal, as assessed by a neurologist. The EEG will be performed under basic conditions and during hyperventilation and intermittent photic stimulation at Screening
  • Body mass index (BMI; weight [in kilogram]/height [in square meter]) between 18 and 30 kilogram per square meter (inclusive), and body weight not less than 50 kilogram at Screening
  • Blood pressure between 90 and 140 millimeter of mercury (mm Hg) systolic (inclusive) and no higher than 90 mm Hg diastolic
  • An average of triplicate 12-lead electrocardiogram (ECG) recordings (performed in a semi-supine position), completed within 4 minutes total, consistent with normal cardiac conduction and function at Screening, including: 1- Sinus rhythm with heart rate between 40 and 100 beats per minute (inclusive); 2- QTc interval between 350 to 450 milliseconds (inclusive); 3- QRS interval of less than 110 milliseconds; 4- PR interval less than 200 milliseconds; 5- ECG morphology consistent with healthy cardiac conduction and function

Exclusion Criteria:

  • Personal or family history of epileptic seizures or convulsions (genetic or idiopathic seizures), or have suffered from head trauma with loss of consciousness, central nervous system infection, or loss of consciousness of unknown origin
  • History of additional risk factors for torsades de pointes (TdP) or the presence of a family history of short QT syndrome, long QT syndrome, sudden unexplained death at a young age ( less than equal to 40 years), drowning or sudden infant death syndrome in a first degree relative (that is, biological parent, sibling, or child)
  • Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or before the first dose of study drug on Day -1 of each treatment period as assessed by the Investigator. Note that participants who have serum potassium, magnesium, or calcium levels outside of the local laboratory's reference range will be excluded
  • Clinically significant abnormal physical examination or vital signs at Screening or before the first dose of study drug on Day -1 of each treatment period as assessed by the Investigator
  • History of drug or alcohol abuse within 5 years before Screening or positive test result(s) for alcohol or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines, hallucinogens, and benzodiazepines) at Screening or on Day -1 of each treatment period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Treatment Sequence 1
Participants will receive treatment A (2*50 milligram [mg] tramadol hydrochloride [HCl] immediate release [IR] tablet + 1 tramadol HCl placebo every 6 hours on Days 1, 2, and 3, along with single dose of 2*50 mg tramadol HCl IR tablet + 1 tramadol HCl placebo + 1 moxifloxacin placebo on Day 4); treatment B (3*50 mg tramadol HCl IR tablet every 6 hours on Days 1, 2, and 3, along with single dose of 3*50 mg tramadol HCl IR tablet + 1 moxifloxacin placebo on Day 4); treatment C (3 tramadol HCl placebo every 6 hours on Days 1, 2, and 3, along with single dose of 3 tramadol HCl placebo + 1 moxifloxacin placebo on Day 4); and treatment D (3 tramadol HCl placebo every 6 hours on Days 1, 2, and 3, along with single dose of 3 tramadol HCl placebo + 1 moxifloxacin placebo on Day 4) in 4 treatment periods as per protocol defined sequence. A washout period of 7 to 15 days will be maintained between each treatment period.
Drug: Tramadol HCl
Tramadol HCl 50 mg immediate release (IR) tablet administered orally.
Other Names:
  • RWJ-26898-002
Drug: Moxifloxacin 400 mg
Moxifloxacin 400 mg tablet administered orally.
Other Names:
  • Avelox
Drug: Tramadol HCl Placebo
Placebo matched to tramadol HCl IR tablet administered orally.
Drug: Moxifloxacin Placebo
Placebo matched to Moxifloxacin 400 mg tablet administered orally.
EXPERIMENTAL: Treatment Sequence 2
Participants will receive treatment A; treatment B; treatment C; and treatment D in 4 treatment periods as per protocol defined sequence. A washout period of 7 to 15 days will be maintained between each treatment period.
Drug: Tramadol HCl
Tramadol HCl 50 mg immediate release (IR) tablet administered orally.
Other Names:
  • RWJ-26898-002
Drug: Moxifloxacin 400 mg
Moxifloxacin 400 mg tablet administered orally.
Other Names:
  • Avelox
Drug: Tramadol HCl Placebo
Placebo matched to tramadol HCl IR tablet administered orally.
Drug: Moxifloxacin Placebo
Placebo matched to Moxifloxacin 400 mg tablet administered orally.
EXPERIMENTAL: Treatment Sequence 3
Participants will receive treatment A; treatment B; treatment C; and treatment D in 4 treatment periods as per protocol defined sequence. A washout period of 7 to 15 days will be maintained between each treatment period.
Drug: Tramadol HCl
Tramadol HCl 50 mg immediate release (IR) tablet administered orally.
Other Names:
  • RWJ-26898-002
Drug: Moxifloxacin 400 mg
Moxifloxacin 400 mg tablet administered orally.
Other Names:
  • Avelox
Drug: Tramadol HCl Placebo
Placebo matched to tramadol HCl IR tablet administered orally.
Drug: Moxifloxacin Placebo
Placebo matched to Moxifloxacin 400 mg tablet administered orally.
EXPERIMENTAL: Treatment Sequence 4
Participants will receive treatment A; treatment B; treatment C; and treatment D in 4 treatment periods as per protocol defined sequence. A washout period of 7 to 15 days will be maintained between each treatment period.
Drug: Tramadol HCl
Tramadol HCl 50 mg immediate release (IR) tablet administered orally.
Other Names:
  • RWJ-26898-002
Drug: Moxifloxacin 400 mg
Moxifloxacin 400 mg tablet administered orally.
Other Names:
  • Avelox
Drug: Tramadol HCl Placebo
Placebo matched to tramadol HCl IR tablet administered orally.
Drug: Moxifloxacin Placebo
Placebo matched to Moxifloxacin 400 mg tablet administered orally.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in QTc Interval
Time Frame: Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4
The QT interval corrected for heart rate (QTc interval) using Fridericia, Bazett and study-specific power correction methods, will be measured by electrocardiograms (ECG).
Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in HR, QRS, and PR Intervals
Time Frame: Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4
The HR, QRS, and PR Intervals, will be measured by ECG.
Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4
Number of Participants with T-wave and U-wave Morphological Changes
Time Frame: Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4
The number of participants having T wave morphology changes from baseline and/or the occurrence of abnormal U-waves that represent the appearance or worsening of the morphological abnormality will be reported.
Baseline (pre-dose, Day1); pre-dose up to 24 hours post-dose on Day 4
Maximum Plasma Concentration During a Dosing Interval at Steady State (Cmax,ss)
Time Frame: Pre-dose up to 24 hours post-dose on Day 4
The Cmax,ss is the maximum plasma concentration at steady state which will be observed during a dosing interval.
Pre-dose up to 24 hours post-dose on Day 4
Trough Plasma Concentration Before Dosing (pre-dose) At Steady State (Ctrough,ss)
Time Frame: Pre-dose up to 24 hours post-dose on Day 4
The Ctrough,ss refers to the drug concentration at steady state, at the time when it is expected to reach its minimum (trough) concentration.
Pre-dose up to 24 hours post-dose on Day 4
Time to Reach the Maximum Plasma Concentration at Steady State (Tmax,ss)
Time Frame: Pre-dose up to 24 hours post-dose on Day 4
The Tmax,ss is the time to reach maximum plasma concentration at steady state which will be observed during a dosing interval.
Pre-dose up to 24 hours post-dose on Day 4
Area Under the Plasma Concentration-Time Curve During a Dosing Interval (tau) at Steady State (AUCtau,ss)
Time Frame: Pre-dose up to 24 hours post-dose on Day 4
The AUC (tau,ss) is the area under the plasma concentration time curve observed during a dosing interval (tau) at steady state.
Pre-dose up to 24 hours post-dose on Day 4
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Time Frame: Screening up to end of study (30 days after the last dose of study drug or early withdrawal)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Screening up to end of study (30 days after the last dose of study drug or early withdrawal)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Scientific Affairs, LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bausch Health Americas, Inc.
Cipher Pharmaceuticals Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 4, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 22, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 27, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 29, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR106355
  • TRAMPAI1003 (OTHER: Janssen Scientific Affairs, LLC)
  • V01-TRAA-401 (OTHER: Valeant Pharmaceuticals International Inc)
  • 2014-01-00 (OTHER: Cipher Pharmaceuticals Inc)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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