Study in Subjects Undergoing Complete Abdominoplasty

A Phase 2, Randomized, Double-blind, Placebo-Controlled Efficacy, Pharmacokinetics and Safety Study of CA-008 in Subjects Undergoing Complete Abdominoplasty

Phase 2, single center, randomized, double-blind, placebo-controlled, parallel design study of CA-008 vs. placebo in subjects undergoing an elective C-ABD under general anesthesia supplemented with a bupivacaine hydrochloride (HCl)transverse abdominis plane (TAP) block.

Study Overview

• Status: Completed
• Conditions: Postsurgical Pain
• Intervention / Treatment: Drug: CA-008 5 mg; Drug: Bupivacaine Hydrochloride; Drug: Hydromorphone; Drug: Fentanyl; Drug: Acetaminophen; Drug: Oxycodone; Drug: Placebo; Drug: CA-008 10 mg; Drug: CA-008 15 mg

Detailed Description

This is a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel design study evaluating up to 4 ascending dose level cohorts, each evaluating a single dose of CA-008 vs. placebo injected/instilled during an elective C-ABD. Up to 72 subjects may be randomized in 4 cohorts.

For each subject, postsurgical assessments will be conducted in two parts:

• Inpatient period: starts with completion of study treatment injection (T0) and continues through 96 hours (T96h).
• Outpatient period: begins on discharge from the inpatient unit through various follow up visits to day 29 (D29)/week 4 (W4) after surgery. Note that additional follow up visits may occur at any time or even after D29/W4 to follow adverse events (AEs) to resolution or establishment of a new baseline.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Plan to undergo an elective complete abdominoplasty (C-ABD), without collateral procedure or additional surgeries.
• In the medical judgment of the investigator, be a reasonably healthy adult aged 18 - 65 years old, inclusive, and American Society of Anesthesiology (ASA) physical Class 1 or 2 at the time of randomization.
• Unless the subject has a same sex partner, he or she must either be sterile (surgically or biologically) or commit to an acceptable method of birth control while participating in the study.
• Have a body mass index ≤ 35 kg/m².
• Be willing and able to sign the informed consent form (ICF) approved by an Institutional Review Board (IRB).

Key Exclusion Criteria:

• In the opinion of the Investigator, have a concurrent painful condition that may require analgesic treatment during the study period or may confound post-surgical pain assessments.
• Have a known allergy to chili peppers, capsaicin or the components of CA-008, acetaminophen, bupivacaine, fentanyl hydromorphone or oxycodone.
• As determined by the investigator have a history or clinical manifestation of significant medical, neuropsychiatric or other condition, including a clinically significant existing arrhythmia, left bundle branch block or abnormal ECG, myocardial infarction or coronary arterial bypass graft surgery within the prior 12 months, significant abnormal clinical laboratory test value, or known bleeding abnormality that could preclude or impair study participation or interfere with study assessments.

• The following are considered disallowed medications:

  1. Be tolerant to opioids defined as those who have been receiving or have received chronic opioid therapy greater than 15 mg of oral morphine equivalents per day for greater than 3 out of 7 days per week over a one-month period within 6 months of screening.
  2. Within 1 day prior to surgery and throughout the inpatient period, be taking any capsaicin-containing products, such as dietary supplements or over-the-counter (OTC) preparations, including topical formulations, and prescription medications.
  3. Within the 7 days prior to surgery, be taking any central nervous system (CNS) active agent as an analgesic adjunct medication, such as anticonvulsants, antidepressants, benzodiazepines, sedative- hypnotics, clonidine and other central alpha-2 agents, ketamine or muscle relaxants.

  i. These drugs are permitted if prescribed for non-pain indications and the dose has been stable for at least 30 days prior to surgery.

ii. The use of benzodiazepines and the non-benzodiazepines are permitted to treat insomnia during the postoperative period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CA-008 5 mg (0.05 mg/mL) Cohort 1; Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).	Drug: CA-008 5 mg; 5 mg CA-008 reconstituted in saline.; Other Names: Vocacapsaicin; Drug: Bupivacaine Hydrochloride; 0.25% administered pre-surgery; Drug: Hydromorphone; 0.02 mg/kg IV administered intraoperatively; Drug: Fentanyl; 100 mcg IV administered intraoperatively; Drug: Acetaminophen; 1000 mg IV administered intraoperatively; Drug: Oxycodone; 5-10 mg PO administered post-surgery
Placebo Comparator: Placebo for Cohort 1; Cohort 1: Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator. The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).	Drug: Bupivacaine Hydrochloride; 0.25% administered pre-surgery; Drug: Hydromorphone; 0.02 mg/kg IV administered intraoperatively; Drug: Fentanyl; 100 mcg IV administered intraoperatively; Drug: Acetaminophen; 1000 mg IV administered intraoperatively; Drug: Oxycodone; 5-10 mg PO administered post-surgery; Drug: Placebo; Each cohort will use placebo reconstituted in saline.
Active Comparator: CA-008 10 mg (0.1 mg/mL); Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).	Drug: Bupivacaine Hydrochloride; 0.25% administered pre-surgery; Drug: Hydromorphone; 0.02 mg/kg IV administered intraoperatively; Drug: Fentanyl; 100 mcg IV administered intraoperatively; Drug: Acetaminophen; 1000 mg IV administered intraoperatively; Drug: Oxycodone; 5-10 mg PO administered post-surgery; Drug: CA-008 10 mg; 10 mg CA-008 reconstituted in saline.; Other Names: Vocacapsaicin
Active Comparator: CA-008 15 mg (0.15 mg/mL); Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).	Drug: Bupivacaine Hydrochloride; 0.25% administered pre-surgery; Drug: Hydromorphone; 0.02 mg/kg IV administered intraoperatively; Drug: Fentanyl; 100 mcg IV administered intraoperatively; Drug: Acetaminophen; 1000 mg IV administered intraoperatively; Drug: Oxycodone; 5-10 mg PO administered post-surgery; Drug: CA-008 15 mg; 15 mg CA-008 reconstituted in saline.; Other Names: Vocacapsaicin
Placebo Comparator: Placebo for Cohorts 2 and 3; Cohorts 2 & 3: Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator. The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg).	Drug: Bupivacaine Hydrochloride; 0.25% administered pre-surgery; Drug: Hydromorphone; 0.02 mg/kg IV administered intraoperatively; Drug: Fentanyl; 100 mcg IV administered intraoperatively; Drug: Acetaminophen; 1000 mg IV administered intraoperatively; Drug: Oxycodone; 5-10 mg PO administered post-surgery; Drug: Placebo; Each cohort will use placebo reconstituted in saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS)	Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 96 hours	96 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores	Pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) from 0 to T96 hours	0 to 96 hours
Total Opioid Consumption	The sum of daily opioid consumption (in morphine equivalents)	0 to 96 hours
Time to Opioid Cessation or Freedom	Time to the last use of opioid	From Surgery to Day 29
Percent of Opioid Free Subjects	Percent of subjects who were opioid free at 24-96 hours	24 to 96 hours

Collaborators and Investigators

• Sponsor: Concentric Analgesics
• Investigators: Principal Investigator: Alina Beaton, MD, Lotus Clinical Research, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): May 16, 2019
• Study Completion (Actual): June 12, 2019

Study Registration Dates

• First Submitted: December 2, 2018
• First Submitted That Met QC Criteria: December 26, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics, Local; Fentanyl; Acetaminophen; Bupivacaine; Oxycodone; Hydromorphone
• Other Study ID Numbers: CA-PS-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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