A Study of MDT-10013 in the Treatment of Acute Postoperative Pain Following Bunionectomy

NCT02077140 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: P13-01
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of MDT-10013 in men and women 18 to 80 years of age who are undergoing bunionectomy. The primary objective is to determine the analgesic efficacy of MDT-10013 compared with standard of care in the treatment of acute postoperative pain after subjects undergo bunionectomy.

Conditions

Postoperative Pain

Outcome Measures

Primary Outcomes (4)

• Summed Pain Intensity Over 1- 48hrs (SPI-48) From Cohort 1 to 3

  Summed pain intensity is a time-weighted average pain score in numeric rating scale (NRS) over 1 to 48hrs (SPI-48). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). The theoretical range for SPI-48 is 0 to 470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Time 0 was defined as the time the capsule was closed.

  over 1 to 48hrs

• Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Last Observation Carried Forward (LOCF)

  Similar to SPI-48, the theoretical range for this LOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical to SPI-48 in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to rescue is carried forward through 48 hours, replacing the raw NRS scores post-rescue for each patient as applicable.

  over 1 to 48hrs

• Integrated Summed Pain Intensity Over 1- 48hrs (SPI-48) and Total Opioid Intake in First 48hrs --Sensitivity Analysis Using Silverman Method

  This sensitivity analysis is an integrated assessment of summed pain intensity over 1 to 48hrs (SPI-48) and total opioid intake (ME0-48) in first 48hrs. Briefly, subjects were ranked according to SPI-48 regardless of the treatment received (including Standard of Care, SOC). The mean of all the ranks for this variable was calculated. Then, the percent difference for each individual rank from the pooled mean rank was computed. This process was repeated for total opioid intake in the first 48hrs (ME0-48). The integrated endpoint for each subject was the sum of the rank order percent differences for SPI-48 and ME0-48. The theoretical minimum and maximum on the integrated endpoint are -197% and +197% in this study. Lower scores are better, indicative of less pain and/or less opioid intake.

  over 1 to 48hrs

• Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Windowed Worst Observation Carried Forward (WOCF)

  Similar to SPI-48, the theoretical range for this WOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to each instance of rescue medication is carried forward through for a window based on the approximate half-life of the drug, replacing the raw NRS scores post-rescue for each patient until the end of the pharmacological activity window, at which point calculations revert to raw NRS as applicable. Note that WOCF SPI-48 may include multiple adjustment windows for each patient, depending on the number or rescue events and the active life of the medication selected.

  over 1 to 48hrs

Secondary Outcomes (4)

• Summed Pain Intensity Scores Over 1- 24hrs (SPI-24), 1- 72hrs (SPI-72) and 1- 96hrs (SPI-96)

  over 1 to 24hrs, 1 to 72hrs, and 1 to 96hrs

• Total Use of Opioid Analgesia Over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs.

  over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs

• Time to First Use of Opioid Analgesia

  up to 96hrs

• Subject's Satisfaction With Study Treatment

  up to 72hrs

Other Outcomes (11)

• Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)

  up to 10 days

• Pharmacokinetic (PK) Parameters of MDT-10013: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞)

  up to 10 days

• Pharmacokinetic (PK) Parameters of MDT-10013: Maximum Observed Plasma Concentration (Cmax)

  up to 10 days

Study Arms (2)

MDT-10013

EXPERIMENTAL

Subjects will receive MDT-10013.

Drug: MDT-10013

Standard of Care

ACTIVE COMPARATOR

Subjects will receive standard of care.

Drug: Standard of care for pain

Interventions

MDT-10013 DRUG

MDT-10013

Standard of care for pain DRUG

Standard of Care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female aged 18 to 80 years.
• Has a body mass index from 18 kg/m2 to 40 kg/m2.
• Is scheduled to undergo primary, unilateral, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
• Is classified by American Society of Anesthesiologists Physical Status Classification System as Class I or II.
• Must meet the following criteria if female:
• Is of non-childbearing potential, defined as any woman who has undergone surgical sterilization or is more than 2 years postmenopausal
• If of childbearing potential, may be enrolled on the condition that results of a pregnancy test are negative at baseline (at Screening and before surgery) and that 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)
• Has read, understood, and signed the informed consent prior to 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.
• Has medical history, physical examination, vital signs, laboratory tests, and 12-lead electrocardiograms (ECGs) that are normal or without clinically relevant abnormalities as per investigator's judgment.

You may not qualify if:

• Is a female who is pregnant or breastfeeding.
• Is not indicated for surgery because of an inflammatory process or risk of infection or delayed wound healing (e.g., autoimmune disorder).
• Has a history of allergy or hypersensitivity to the components in the investigational product or to the opioid medication (oxycodone).
• Before surgery, has current orthostatic hypotension (defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg or an increase in heart rate by 20 beats per minute within 3 minutes of sitting up or standing).
• Has a current gastrointestinal disorder associated with bleeding, a history of such a disorder, or gastrointestinal inflammatory diseases as Crohn's disease or ulcerative colitis.
• Has any clinically significant cardiovascular condition as evidenced by physical examination, medical history, and/or baseline ECG.
• Has evidence of bradycardia as shown by heart rate of \<50 beats per minute via screening ECG.
• Has a known infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
• Has a chronic pain condition that may interfere with the subject's assessment of pain postoperatively, as determined by the investigator.
• Has any poorly controlled or serious medical conditions, psychiatric illnesses, or clinically significant laboratory values that, in the opinion of the investigator, could compromise the safety of the subject or the scientific integrity of the study (e.g., uncontrolled hypertension, autoimmune disease, or clinically relevant symptoms of thyroid dysfunction).
• Has presence or history of local or systemic malignant disease in the past 5 years (history of basal cell carcinoma will be allowed).
• Has impaired renal function (creatinine \>1.5 times upper limit of normal).
• Has chronic impairment liver function (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).

Sponsors & Collaborators

• Medtronic Spinal and Biologics: lead

Study Sites (2)

Research Site

Phoenix, Arizona, 85027, United States

Location

Research Site

Austin, Texas, 78705, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Clinical Affairs
• Organization: Medtronic Spine and Biologics

msbkclinicalresearch@medtronic.com

1800-876-3133

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: March 4, 2014
• Study Start: February 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: February 1, 2016
• Last Updated: October 13, 2017
• Results First Posted: October 13, 2017

Record last verified: 2017-09

Locations

US (2)