Tramadol Versus Placebo and Morphine in the Management of Post-Operative Pain Abdominoplasty

A Phase 3, Multicenter, Randomized, Double-Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo and Morphine in the Management of Postoperative Pain Following Abdominoplasty

This study is evaluating the analgesic efficacy of intravenous (IV) tramadol (AVE-901) compared to placebo in the management of postoperative pain following abdominal surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Pain Management
• Intervention / Treatment: Drug: Tramadol; Drug: Morphine; Other: Placebo

Detailed Description

(Non-clinical summary) Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioid-like effects. Tramadol is extensively metabolized following administration, which results in a number of enantiomeric metabolites that display different opioid-receptor binding properties, and monoaminergic reuptake inhibition.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Texas
    • Houston, Texas, United States, 77004
      • Hermann Drive Research
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient is male or female 18-75 years of age
• Willing to give consent and able to understand the study procedures
• Female patients must be of non-childbearing potential or be practicing a highly effective contraption
• The patient must be willing to be housed in a healthcare facility and able to receive parenteral analgesia for at least 48 hours after surgery
• The patient meets definition of American Society of Anesthesiologists (ASA) Physical Class 1, or 2.

Exclusion Criteria:

• The patient is undergoing an abdominoplasty of significant complexity defined as pre-planned surgical time of greater than 180 mins.
• The patient has a recent (within 5 years) and/or current history of chronic analgesic, opiate or tranquilizer abuse or dependence or is a user of illicit drugs or has had a recent history (within 2 years) of drug or alcohol abuse.
• The patient is taking herbal or dietary supplements or medications that are moderate or strong inhibitors of CYP2D6 or CYP3A4 (e.g., fluoxetine, paroxetine, amitriptyline, quinidine, ketoconazole, erythromycin, grapefruit juice) or inducers of CYP3A4 (e.g., carbamazepine, rifampin, St. John's Wort) and cannot go through a minimum washout period of 14 days prior to surgery.
• The patient has a history of epilepsy, is susceptible to seizures.
• The patient cannot be withdrawn from medications (at least 7 days prior to surgery) that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or which increase serotonergic tone (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, triptans, cyclobenzaprine triptans).
• The patient has had a recent cardiovascular event or clinically significant abnormal ECG finding at screening or baseline.
• The patient has a history of Long QT Syndrome or a relative with this condition.
• The patient has expressed suicidal ideation or is considered to be at risk of suicide.
• The patient is morbidly obese (body mass index [BMI] ≥ 40 kg/m2) or has documented sleep apnea requiring CPAP or other treatment.
• Female patient is pregnant and/or undergoing a pregnancy-related surgery, or breastfeeding.
• The patient has a history of cardiopulmonary, neurological or psychiatric or other medical condition that may confound the assessments of efficacy or safety.
• The patient has cirrhosis, moderate or severe hepatic impairment or an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value > 3X upper limit of normal (ULN) at Screening.
• The patient has severe renal impairment or a serum creatinine value of > 2.0 mg/dL at Screening.
• The patient has potassium, sodium, calcium or magnesium levels outside of the normal range or any other clinically significant abnormalities in laboratory values at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tramadol 50 mg; Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44	Drug: Tramadol; IV Tramadol 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
Active Comparator: Morphine 4 mg; Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44	Drug: Morphine; Morphine 4 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
Placebo Comparator: Placebo; Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44	Other: Placebo; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Sum of Pain Intensity Differences through 24 hours	24 hours post dose

Collaborators and Investigators

• Sponsor: Avenue Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Anticipated): May 30, 2019
• Study Completion (Anticipated): June 30, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 13, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2019
• Last Update Submitted That Met QC Criteria: May 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine; Tramadol
• Other Study ID Numbers: AVE-901-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No