Study to Evaluate the Safety and Tolerability of FX301 in Patients Undergoing Bunionectomy

NCT04826328 | Completed Phase 1 FDA Drug

• 1 other identifier: FX301-2020-001
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This two-part study will be conducted in male and female patients 18 to 65 years of age undergoing bunionectomy. Part I - three-step, single ascending dose study design in which two drug loads (low drug load of funapide and high drug load of funapide) and two volumes (high volume and low volume) of FX301 will be explored against placebo in four cohorts of 12 patients each (9 active:3 placebo) for the management of post-surgical pain in patients undergoing bunionectomy. Part II - expansion cohort to further assess safety, tolerability, systemic exposure, and efficacy of a selected drug load/volume of FX301. An additional 36 patients will be randomized in a 1:1 ratio to receive either FX301 or placebo as a single-injection analgesic nerve block adjacent to the sciatic nerve of the popliteal fossa.

Conditions

Pain, Postoperative; Bunion

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events after FX301 is administered as a single-dose, analgesic nerve block

  Incidence of treatment emergent adverse events after a single analgesic nerve block of FX301

  Baseline to Day 85

Secondary Outcomes (2)

• Efficacy of FX301 in the management of acute post-surgical pain

  Baseline to 72 Hours

• Characterization of the systemic exposure of funapide as seen through the pharmacokinetic (PK) analysis at Days 1-6, 8, 15, 29, 57, and 85.

  Baseline to Day 85

Study Arms (5)

FX301 Low Dose Low Volume

EXPERIMENTAL

65 mg of funapide given as a single injection nerve block adjacent to the sciatic nerve of the popliteal fossa

Drug: FX301

FX301 Low Dose High Volume

EXPERIMENTAL

130 mg of funapide given as a single injection nerve block adjacent to the sciatic nerve of the popliteal fossa

Drug: FX301

FX301 High Dose Low Volume

EXPERIMENTAL

130 mg of funapide given as a single injection nerve block adjacent to the sciatic nerve of the popliteal fossa

Drug: FX301

FX301 High Dose High Volume

EXPERIMENTAL

260 mg of funapide given as a single injection nerve block adjacent to the sciatic nerve of the popliteal fossa

Drug: FX301

Normal Saline

PLACEBO COMPARATOR

Low or high matching volume of preservative-free normal saline given as a single injection adjacent to the sciatic nerve of the popliteal fossa

Drug: Normal Saline

Interventions

FX301 DRUG

FX301 is an extended-release formulation of funapide being developed as a single injection peripheral nerve block for the management of acute postsurgical pain

Also known as: funapide

FX301 High Dose High Volume; FX301 High Dose Low Volume; FX301 Low Dose High Volume; FX301 Low Dose Low Volume

Normal Saline DRUG

Single peripheral nerve injection

Normal Saline

Eligibility Criteria

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

You may qualify if:

• Written consent to participate in the study
• Be willing and able to complete study procedures and pain scales, follow instructions and communicate meaningfully in English with study personnel, and return for outpatient follow-up visits as required.
• Male or female ≥18 to ≤65 years of age, inclusive
• Planning to undergo an elective primary unilateral, distal, first metatarsal bunionectomy with osteotomy and internal fixation, without collateral procedure or additional surgeries, to be performed under Monitored Anesthesia Care (MAC) and be eligible to receive a popliteal sciatic nerve block
• Classified as either ASA 1 or ASA 2 by the American Society of Anesthesiologists Physical Status Classification System (Appendix 1).
• Has a BMI of ≥18 to ≤ 35 kg/m2.
• Willing to washout from all prohibited medications for the longer of 14 days or five half-lives prior to dosing, and abstain from those medications through the end of study (Appendix 5).
• If a male, unless he has a same sex partner, be either sterile (surgically or biologically) or commit to an acceptable method of birth control while participating in the study.
• If a woman of childbearing potential (WOCBP), must meet all of the following:
• Not be pregnant (WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy test before surgery);
• Not plan to become pregnant or to breast feed during the study; and
• Be surgically sterile (at least one year post total hysterectomy, bilateral oophorectomy or bilateral tubal ligation) or at least one year post-menopausal, have a monogamous partner who is surgically sterile, have a same sex partner, or (one of the following must apply):
• is practicing double-barrier contraception
• is practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity)
• is using a non-hormonal contraceptive approved by the FDA for at least 2 months prior to screening and commits to the use of an acceptable form of birth control while participating in the study..

You may not qualify if:

• Has a concurrent painful condition, other than bunion-related pain, that may require analgesic treatment during the study period or may confound post-surgical pain assessments.
• Has an active skin disease or other clinically significant abnormality at the anticipated site of surgery or nerve block insertion site that could interfere with the planned surgery.
• Has had previous bunionectomy or other surgical procedure on the index foot that could impact the current bunion surgery.
• Has any clinically significant cardiac, respiratory, neurological, immunological, hematological, or renal disease or any other condition that, in the opinion of the investigator, could compromise the subject's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
• Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any NSAIDs; history of NSAID-induced bronchospasm (subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to any other drugs used in the study, including anesthetics and antibiotics that may be required on the day of surgery.
• Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
• Has taken any opioids, NSAIDS, or acetaminophen within 3 days prior to the scheduled surgery. Low dose aspirin (\<100 mg) for cardiovascular protection is acceptable.
• Has initiated treatment with any of the following medications within 30 days prior to study medication administration or is taking any of these medications to control pain: selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, gabapentin, pregabalin, or cyclooxygenase-2 inhibitors. (Note: If a subject is taking one of these medications for a reason other than pain control, the subject must be on a stable scheduled dose \[i.e., not "as needed"\] for at least 1 month prior to study medication administration.)
• Within the 14 days prior to surgery, be taking parenteral or oral corticosteroids (steroid inhalers for allergy or asthma treatment, topical steroids for a non-clinically significant skin condition not involving the area of surgery, or ophthalmic steroids are permissible).
• Is currently receiving antianginal therapy
• Has a known or suspected history of alcoholism or drug abuse or misuse within 1 year of screening or evidence of opioid tolerance or physical dependence before dosing with the study medication.
• Has positive results on the alcohol test (breath or saliva) indicative of alcohol abuse or urine drug screen (UDS) indicative of illicit drug use at screening, and/or prior to surgery. Note that for those subjects have a history of, or who test positive for tetrahydrocannabinol (THC), if they are willing to abstain from use or consumption of THC-containing products from 14 days prior to surgery to Day 85, they may be allowed to participate in the study. Additionally, it may be permissible for the subject to participate if the results of the UDS can be explained by a current prescription or acceptable over-the-counter medication as determined by the investigator at screening and/or prior to surgery.
• Has significant difficulties swallowing tablets or is unable to tolerate oral medication.
• Has received any investigational drug or device or investigational therapy within the last 30 days.
• Has a history of a clinically significant (in the investigator's opinion) GI event within 6 months before screening or has any history of peptic or gastric ulcers or GI bleeding.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead
• Lotus Clinical Research, LLC: collaborator

Study Sites (1)

Lotus Clinical Research, Huntington Hospital

Pasadena, California, 91105, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Bunion

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Foot Deformities, Acquired; Foot Deformities; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• William T Andrews, MD, FACP

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

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

Model Details: Part I - Double-Blind, placebo-controlled, three-step, Single Ascending Dose Part II - Double Blind, placebo-controlled, Expansion Phase to enroll additional patients to an SMC-cleared dose/volume level

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 1, 2021
• Study Start: March 15, 2021
• Primary Completion: January 11, 2022
• Study Completion: March 30, 2022
• Last Updated: August 26, 2022

Record last verified: 2022-08

Locations

US (1)