Study in Subjects Undergoing Complete Abdominoplasty

Concentric Analgesics

Status and phase: Completed; Phase 2

Conditions: Postsurgical Pain

Treatments: Drug: CA-008 15 mg; Drug: Placebo; Drug: Hydromorphone; Drug: Bupivacaine Hydrochloride; Drug: Acetaminophen; Drug: CA-008 10 mg; Drug: Fentanyl; Drug: CA-008 5 mg; Drug: Oxycodone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03789318

CA-PS-204

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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54 participants in 5 patient groups, including a placebo group

CA-008 5 mg (0.05 mg/mL) Cohort 1

Active Comparator group

Description:

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).

Treatment:

Drug: Bupivacaine Hydrochloride

Drug: CA-008 5 mg

Drug: Acetaminophen

Drug: Oxycodone

Drug: Hydromorphone

Drug: Fentanyl

Placebo for Cohort 1

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

Drug: Bupivacaine Hydrochloride

Drug: Acetaminophen

Drug: Oxycodone

Drug: Hydromorphone

Drug: Fentanyl

CA-008 10 mg (0.1 mg/mL)

Active Comparator group

Description:

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).

Treatment:

Drug: Bupivacaine Hydrochloride

Drug: Acetaminophen

Drug: Oxycodone

Drug: CA-008 10 mg

Drug: Hydromorphone

Drug: Fentanyl

CA-008 15 mg (0.15 mg/mL)

Active Comparator group

Description:

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).

Treatment:

Drug: Bupivacaine Hydrochloride

Drug: Acetaminophen

Drug: Oxycodone

Drug: Hydromorphone

Drug: CA-008 15 mg

Drug: Fentanyl

Placebo for Cohorts 2 and 3

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

Drug: Bupivacaine Hydrochloride

Drug: Acetaminophen

Drug: Oxycodone

Drug: Hydromorphone

Drug: Fentanyl