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

NCT ID: NCT02307864

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-04
• Study Completion Date: 2015-08-27

Brief Summary

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).

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tramadol HCl

Intervention Type: DRUG

Tramadol HCl 50 mg immediate release (IR) tablet administered orally.

Moxifloxacin 400 mg

Intervention Type: DRUG

Moxifloxacin 400 mg tablet administered orally.

Tramadol HCl Placebo

Intervention Type: DRUG

Placebo matched to tramadol HCl IR tablet administered orally.

Moxifloxacin Placebo

Intervention Type: DRUG

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

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.

Group Type: EXPERIMENTAL

Tramadol HCl

Intervention Type: DRUG

Tramadol HCl 50 mg immediate release (IR) tablet administered orally.

Moxifloxacin 400 mg

Intervention Type: DRUG

Moxifloxacin 400 mg tablet administered orally.

Tramadol HCl Placebo

Intervention Type: DRUG

Placebo matched to tramadol HCl IR tablet administered orally.

Moxifloxacin Placebo

Intervention Type: DRUG

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

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.

Group Type: EXPERIMENTAL

Tramadol HCl

Intervention Type: DRUG

Tramadol HCl 50 mg immediate release (IR) tablet administered orally.

Moxifloxacin 400 mg

Intervention Type: DRUG

Moxifloxacin 400 mg tablet administered orally.

Tramadol HCl Placebo

Intervention Type: DRUG

Placebo matched to tramadol HCl IR tablet administered orally.

Moxifloxacin Placebo

Intervention Type: DRUG

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

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.

Group Type: EXPERIMENTAL

Tramadol HCl

Intervention Type: DRUG

Tramadol HCl 50 mg immediate release (IR) tablet administered orally.

Moxifloxacin 400 mg

Intervention Type: DRUG

Moxifloxacin 400 mg tablet administered orally.

Tramadol HCl Placebo

Intervention Type: DRUG

Placebo matched to tramadol HCl IR tablet administered orally.

Moxifloxacin Placebo

Intervention Type: DRUG

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

Interventions

Tramadol HCl

Tramadol HCl 50 mg immediate release (IR) tablet administered orally.

Intervention Type: DRUG

Moxifloxacin 400 mg

Moxifloxacin 400 mg tablet administered orally.

Intervention Type: DRUG

Tramadol HCl Placebo

Placebo matched to tramadol HCl IR tablet administered orally.

Intervention Type: DRUG

Moxifloxacin Placebo

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

Intervention Type: DRUG

Other Intervention Names

RWJ-26898-002; Avelox

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

Cipher Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: collaborator

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

Overland Park, Kansas, United States

Countries

United States

Other Identifiers

TRAMPAI1003

Identifier Type: OTHER

Identifier Source: secondary_id

V01-TRAA-401

Identifier Type: OTHER

Identifier Source: secondary_id

2014-01-00

Identifier Type: OTHER

Identifier Source: secondary_id

CR106355

Identifier Type: -

Identifier Source: org_study_id