A Feasibility Dose-escalating Study of MDT-10013 for Acute Postoperative Pain Following Total Knee Arthroplasty

NCT02263222 | Withdrawn Phase 2 DMC

• 1 other identifier: P13-02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label dose-escalating study to evaluate the tolerability and systemic exposure of MDT-10013 in men and women at least 18 years of age who are undergoing primary unilateral TKA.

Conditions

Post-operation Pain

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic (PK) parameters of MDT-10013--maximum plasma concentration observed (Cmax)

  From day 1 to day 14

• Pharmacokinetic (PK) parameters of MDT-10013--time to maximum plasma concentration observed (tmax)

  From day 1 to day 14

• Pharmacokinetic (PK) parameters of MDT-10013--area under the plasma concentration versus time curve (AUC)

  From day 1 to day 14

• Rate of study drug/treatment-related serious adverse events (SAEs)

  up to 3 months

Secondary Outcomes (6)

• Summed pain intensity scores at rest

  up to 120 hours

• Summed pain intensity scores over 2 to 48 hours (SPI-48) with activity

  up to 48 hours

• Aggregate dosage of all opioid analgesia

  0 to 24 hours and 0 to 48 hours

• Total use of opioid analgesia

  From 48 hours through Day 6/120 hours

• Time to first use of opioid analgesia defined as the time from Time 0 to the first use of opioid analgesia.

  Time 0 is defined as the initiation of arthrotomy closure to the first opioid analgesia use

Study Arms (1)

MDT-10013

EXPERIMENTAL

Subjects will receive MDT-10013.

Drug: MDT-10013

Interventions

MDT-10013 DRUG

MDT-10013

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female at least 18 years of age
• Has a body mass index from 18 kg/m2 to 40 kg/m2
• Is scheduled to undergo standard primary (first-time) unilateral TKA surgery (due to osteoarthritis) with or without patellar resurfacing. Standard conventional instrumentation and cemented components must be used and the surgery shall be conducted under spinal anesthesia.
• Females must meet the following criteria:
• Is of nonchildbearing potential, defined as any woman who has undergone surgical sterilization or is more than 2 years postmenopausal
• If of childbearing potential, may be enrolled if pregnancy test results are negative at Screening and if she is routinely using an effective method of birth control with a low failure rate (i.e., hormonal contraception, intrauterine device, condoms in combination with a spermicidal cream, or total sexual abstinence).
• May not be pregnant or lactating
• Has read, understood, and signed the informed consent before study entry
• Is mentally competent, reliable, and cooperative to undergo all visits and procedures scheduled in the study protocol and to record the required information.

You may not qualify if:

• Has had previous spinal surgery or other contraindications that preclude use of spinal anesthesia or is not indicated for surgery because of an inflammatory process or risk of infection or delayed wound healing (e.g., autoimmune disorder)
• Is scheduled to undergo a concurrent surgical procedure (e.g., bilateral TKA)
• Has a concurrent painful condition or surgery that may require analgesic treatment (such as a nonsteroidal antiinflammatory drug \[NSAID\] or opioid) in the postsurgical period for pain not strictly related to the TKA, and that may confound postsurgical assessments
• Has a history of allergy or hypersensitivity to the components in the investigational product or to the routine care medications
• Has current orthostatic hypotension (i.e., systolic blood pressure decrease of at least 20 mmHg or diastolic blood pressure decrease of at least 10 mmHg or an increase in heart rate of 20 beats per minute within 3 minutes of standing)
• Has any clinically significant cardiovascular condition as evidenced by physical examination, medical history, and/or baseline electrocardiogram (ECG), including inadequately controlled hypertension
• Has evidence of bradycardia as shown by heart rate of \<50 beats per minute via screening ECG
• In the investigator's opinion, subject is not a suitable candidate for study treatment and/or has any poorly controlled or serious medical conditions, psychiatric illnesses, or clinically significant laboratory values that the investigator suspects could compromise the subject's safety or the scientific integrity of the study (e.g., human immunodeficiency virus \[HIV\], hepatitis B or C \[hep B, hep C\])
• Has presence or history of local or systemic malignant disease in the past 5 years (history of basal cell carcinoma will be allowed)
• Has undergone prior open surgery in the affected knee
• Has impaired renal function (creatinine \>1.5 times upper limit of normal)
• Has chronic liver function impairment (aspartate aminotransferase or alanine aminotransferase \>3 times upper limit of normal)
• Has insulin-dependent diabetes or uncontrolled diabetes mellitus (glycosylated hemoglobin \>7%)
• Has leukopenia (\<3500 leukocytes/μL)
• Has current treatment with any of the following medications:

Sponsors & Collaborators

• Medtronic Spinal and Biologics: lead

Study Sites (3)

Achieve Clinical Research, LLC

Birmingham, Alabama, 35216, United States

Location

Florida Research Associates, LLC

DeLand, Florida, 32720, United States

Location

Clinical Research Department, University of Orthopedics Center

Altoona, Pennsylvania, 16602, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 13, 2014
• Study Start: February 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: June 7, 2016

Record last verified: 2016-06

Locations

US (3)