Evaluate Safety of Tramadol in the Management of Postoperative Pain Following Surgery

• Sponsor: Avenue Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03395808
• Collaborator: (none)
• Enrollment: 251
• Location: 1
• Arm: 1
• Actual Duration (Months): 16.4
• Patients Per Site Per Month: 15.3

Study Details

Study Description

Brief Summary

The study evaluates the safety of IV tramadol managing post-operative pain following surgery.

Condition or Disease	Intervention/Treatment	Phase
Pain Management	Drug: Tramadol	Phase 3

Detailed Description

(Non-clinical summary) Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioidlike 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 Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 3, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety of Tramadol Infusion (AVE-901) in the Management of Post-Operative Pain Following Surgery
• Actual Study Start Date: Dec 22, 2017
• Actual Primary Completion Date: Apr 25, 2019
• Actual Study Completion Date: May 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: AVE-901 50mg IV Tramadol	Drug: Tramadol; IV; 50 mg given at Hours 0, 2, 4, 8 and every 4 hours thereafter, for a total of up to 43 doses

Outcome Measures

Primary Outcome Measures

1. Adverse Events [Up to 21 days]

   Reported Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 24 hours after surgery

• The patient meets definition of American Society of Anesthesiologists (ASA) Physical Class 1, or 2.

Exclusion Criteria:

• The patient has used chronic opioid therapy, defined as >= 20 MEQs of morphine per day

=3 days out of 7 days over the past 4 weeks.

• The patient has a recent (within 2 years) and/or current history of alcohol, opiate or tranquilizer abuse or dependence.

• 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 7 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, amphetamines).

• The patient has had a recent (within 6 months) cardiovascular event or clinically significant abnormal ECG finding at screening.

• The patient has a history of Long QT Syndrome or a relative with this condition.

• The patient has expressed suicidal ideation within the past 3 months 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 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 > 2x upper limit of normal (ULN) at Screening.

• The patient has potassium, sodium, calcium or magnesium levels outside of the normal range at Screening.

• The patient has a hemoglobin level at screening which, in the judgment of the Investigator, is not suitable for participation in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lotus Clinical Research	Pasadena	California	United States	91105

Sponsors and Collaborators

• Avenue Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 29, 2018
• Statistical Analysis Plan - Feb 7, 2019

More Information

Publications

None provided.

• Responsible Party: Avenue Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03395808
• Other Study ID Numbers: AVE-901-104
• First Posted: Jan 10, 2018
• Last Update Posted: Mar 9, 2021
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tramadol

Study Results

Participant Flow

Arm/Group Title	AVE-901 50mg
Arm/Group Description	IV Tramadol Tramadol: IV; 50 mg given at Hours 0, 2, 4, 8 and every 4 hours thereafter, for a total of up to 43 doses
Period Title: Overall Study
STARTED	251
COMPLETED	251
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	AVE-901 50mg
Arm/Group Description	IV Tramadol Tramadol: IV; 50 mg given at Hours 0, 2, 4, 8 and every 4 hours thereafter, for a total of up to 43 doses
Overall Participants	251
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	201 80.1%
>=65 years	50 19.9%
Sex: Female, Male (Count of Participants)
Female	151 60.2%
Male	100 39.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	85 33.9%
Not Hispanic or Latino	166 66.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 1.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	43 17.1%
White	203 80.9%
More than one race	1 0.4%
Unknown or Not Reported	1 0.4%
Region of Enrollment (participants) [Number]
United States	251 100%

Outcome Measures

1. Primary Outcome

Title	Adverse Events
Description	Reported Adverse Events
Time Frame	Up to 21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Tramadol 50 mg
Arm/Group Description	50 mg IV tramadol given at 0, 2, 4 hours and every 4 hours after
Measure Participants	251
Count of Participants [Participants]	251 100%

Adverse Events

Time Frame	6 months
Arm/Group Title	AVE-901 50mg
Arm/Group Description	IV Tramadol Tramadol: IV; 50 mg given at Hours 0, 2, 4, 8 and every 4 hours thereafter, for a total of up to 43 doses
All Cause Mortality
	AVE-901 50mg
	Affected / at Risk (%)	# Events
Total	0/251 (0%)
Serious Adverse Events
	AVE-901 50mg
	Affected / at Risk (%)	# Events
Total	2/251 (0.8%)
Investigations
Post procedural hematoma	2/251 (0.8%)	2
Other (Not Including Serious) Adverse Events
	AVE-901 50mg
	Affected / at Risk (%)	# Events
Total	149/251 (59.4%)
Gastrointestinal disorders
Nausea	72/251 (28.7%)
Vomitting	49/251 (19.5%)
Constipation	14/251 (5.6%)
General disorders
Infusion Site pain	13/251 (5.2%)
Investigations
Blood creatine phosphokinase increased	16/251 (6.4%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	17/251 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.