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

NCT02307864 | Completed Phase 1 FDA Drug

• 4 other identifiers: CR106355TRAMPAI1003V01-TRAA-4012014-01-00
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Keywords

Healthy; QT interval; QTc interval; Electrocardiogram; Tramadol hydrochloride; Moxifloxacin; Placebo

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in QTc Interval

  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 Outcomes (7)

• Change From Baseline in HR, QRS, and PR Intervals

  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

  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)

  Pre-dose up to 24 hours post-dose on Day 4

• Trough Plasma Concentration Before Dosing (pre-dose) At Steady State (Ctrough,ss)

  Pre-dose up to 24 hours post-dose on Day 4

• Time to Reach the Maximum Plasma Concentration at Steady State (Tmax,ss)

  Pre-dose up to 24 hours post-dose on Day 4

Study Arms (4)

Treatment Sequence 1

EXPERIMENTAL

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; Drug: Moxifloxacin 400 mg; Drug: Tramadol HCl Placebo; Drug: Moxifloxacin Placebo

Treatment Sequence 2

EXPERIMENTAL

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; Drug: Moxifloxacin 400 mg; Drug: Tramadol HCl Placebo; Drug: Moxifloxacin Placebo

Treatment Sequence 3

EXPERIMENTAL

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; Drug: Moxifloxacin 400 mg; Drug: Tramadol HCl Placebo; Drug: Moxifloxacin Placebo

Treatment Sequence 4

EXPERIMENTAL

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; Drug: Moxifloxacin 400 mg; Drug: Tramadol HCl Placebo; Drug: Moxifloxacin Placebo

Interventions

Tramadol HCl DRUG

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

Also known as: RWJ-26898-002

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Moxifloxacin 400 mg DRUG

Moxifloxacin 400 mg tablet administered orally.

Also known as: Avelox

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Tramadol HCl Placebo DRUG

Placebo matched to tramadol HCl IR tablet administered orally.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Moxifloxacin Placebo DRUG

Placebo matched to Moxifloxacin 400 mg tablet administered orally.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead
• Bausch Health Americas, Inc.: collaborator
• Cipher Pharmaceuticals Inc.: collaborator

Study Sites (1)

Unknown Facility

Overland Park, Kansas, United States

Location

MeSH Terms

Interventions

Tramadol; Moxifloxacin

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: December 4, 2014
• Primary Completion: August 22, 2015
• Study Completion: August 27, 2015
• Last Updated: August 29, 2018

Record last verified: 2018-08

Locations

US (1)