A Phase 2 Study to Evaluate Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy

NCT04495283 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CP-NVK009-0005
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy

Conditions

Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Summed Pain Intensity (SPI) Between Group A and Group C

  Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, was used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: Sum (1/2 (SPIi + SPIi+1)\*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and placebo (Group C) from Hour 0 to Hour 48 (SPI0-48)

  0 to 48 hours

Secondary Outcomes (12)

• Summed Pain Intensity (SPI) Compared Between Group A and Group B

  0 to 48 hours

• Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale From Hour 0 to Hour 12 (SPI0-12), Hour 12 to Hour 24 (SPI12-24), and Hour 24 to Hour 48 (SPI24-48).

  0, 12, 24, 48 hours

• Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale Over Time

  0, 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours

• Number of Participants With Treatment-Related Adverse Events (TRAE)

  7 days

• Percentage of Participants Who Were Opioid Free Over Time

  12 to 48 hours

Study Arms (3)

PGB and APAP (Group A)

EXPERIMENTAL

Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.

Drug: Pregabalin; Drug: Acetaminophen

APAP (Group B)

EXPERIMENTAL

Group B receives placebo 2 prior to surgery and APAP post-surgery.

Drug: Acetaminophen; Other: Placebo 2

Placebo (Group C).

EXPERIMENTAL

Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.

Other: Placebo 1; Other: Placebo 2

Interventions

Pregabalin DRUG

Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.

Also known as: PGB

PGB and APAP (Group A)

Acetaminophen DRUG

Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.

Also known as: APAP

APAP (Group B); PGB and APAP (Group A)

Placebo 1 OTHER

Placebo for APAP

Placebo (Group C).

Placebo 2 OTHER

Placebo for combination

APAP (Group B); Placebo (Group C).

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide informed consent by signing the informed consent form (ICF) approved by the Institutional Review Board (IRB);
• Be male or female aged 18-65 years;
• Be scheduled to undergo unilateral first metatarsal bunionectomy;
• Be in good health and capable of undergoing a bunionectomy under anesthesia as described in the study surgical and anesthetic protocol;
• Weigh between 50 and 100 kg (body mass index \[BMI\] \<32 kg/m2);
• Have no additional planned surgeries other than bunionectomy during the course of the study;
• Have negative urine drug screen for drugs indicative of illicit drug use (unless results can be explained by a current prescription or acceptable over-the-counter medication at screening as determined by the investigator) and no detectable results on the alcohol test (breath or saliva) indicative of alcohol abuse at screening, and/or prior to surgery (may be repeated if the Investigator suspects a false-positive result). Note: For those subjects who test positive for tetrahydrocannabinol (THC), if they are willing to abstain from use or consumption of THC-containing products from screening through end of the subject's participation in the study, they may be allowed to participate in the study.
• Biological female subjects must be non-lactating, sterile (bilateral tubal ligation, bilateral salpingectomy, or hysterectomy), post-menopausal for at least 2 years, have a partner that is sterile, be abstinent, use a highly effective double- contraception method (hormonal protection is insufficient), or use an FDA-approved contraceptive for greater than 2 months prior to the screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after completion of the study;
• Be willing and able to complete the study procedures and pain scales and communicate meaningfully in English with study personnel.

You may not qualify if:

• Have a medical condition or history that in the Investigator's opinion could adversely impact the subject's participation or safety or the conduct of the study, or interfere with the pain assessments, including the following:
• Serious breathing difficulties or respiratory risk factors (including use of opioid pain medicines and other drugs that depress the central nervous system), and conditions such as chronic obstructive pulmonary disease that reduce lung function.
• Hypertension (uncontrolled), cardiovascular disease, or history of cerebrovascular events. Hypertension must be controlled without known end organ damage.
• Concurrent painful conditions that may require analgesic treatment during the study period.
• History of significantly reduced hepatic or renal function, angle closure glaucoma, or convulsive disorder.
• Recent history of urinary retention.
• Opioid tolerant, i.e., the subject is currently taking or has taken a chronic opioid at a dose greater than or equal to 20 mg morphine milligram equivalents (MME) per day (more than 30 consecutive days of daily use) for pain in the 2 months prior to surgery.
• Active cutaneous disease, or other disease, at the surgical site.
• Peripheral vascular disease, sickle cell disease, vascular grafts, or vasospastic disorders.
• Known bleeding disorder or is taking agents affecting coagulation preoperatively.
• Deep venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted postoperatively.
• Diabetes mellitus (uncontrolled). Diabetes mellitus must be controlled without known end organ damage.
• History of malignancy in the past 2 years with the exception of squamous cell carcinoma or basal cell carcinoma.
• Prior bunionectomy on the index foot or other foot surgery on the index foot that could impact the surgery or data collection endpoints.
• Use of disallowed medications including the following:

Sponsors & Collaborators

• Nevakar, Inc.: lead
• Nevakar Injectables, Inc.: collaborator

Study Sites (2)

Lotus Clinical Resarch,LLC

Pasadena, California, 91105, United States

Location

Lotus HD Research

Bellaire, Texas, 77401, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Pregabalin; Prostaglandins B; Acetaminophen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Results Point of Contact

• Title: Eric Lang, MD
• Organization: Nevakar, Inc.

Clinicaltrials@nevakar.com

(908) 367-7400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo). Eligible subjects will be randomized on Day 1 in a 2:2:1 ratio to receive either a combination of PGB and APAP administered (Group A), APAP (Group B), or placebo (Group C).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 31, 2020
• Study Start: July 28, 2020
• Primary Completion: November 12, 2020
• Study Completion: November 12, 2020
• Last Updated: November 23, 2021
• Results First Posted: November 23, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)