Efficacy Studies | XARACOLL® (bupivacaine HCl) implant

Study Design

TWO PHASE III STUDIES IN OPEN INGUINAL HERNIOPLASTY

Two Phase III studies of identical design were performed as outpatient surgeries in adults across 39 sites in the US¹

PATIENT RANDOMIZATION ACROSS BOTH STUDIES (N=610)

PRIMARY ENDPOINT: Time-weighted sum of pain intensity from 0 through 24 hours^‡
SECONDARY ENDPOINT: Total use of opioid analgesia (TOpA)

*Doses above 300 mg per patient have not been studied in clinical trials.
†Intravenous morphine provided until patients were able to tolerate oral morphine.
‡Sum of Pain Intensity is an FDA-accepted measurement of pain, calculated by using patient ratings of pain intensity on a 0-10 scale reported at multiple points from baseline over a time period.³

24-Hour Efficacy

Study 1³

20% Mean Reduction in Pain Intensity^*

XARACOLL: 85.9
Placebo: 106.8
P Value: 0.0004

50% Less Opioid Use^†

XARACOLL: 5 mg
Placebo: 10 mg
P Value: <0.0001

Study 2³

24% Mean Reduction in Pain Intensity^*

XARACOLL: 88.3
Placebo: 116.2
P Value: <0.0001

64% Less Opioid Use^†

XARACOLL: 5 mg
Placebo: 14 mg
P Value: <0.0001

IMPORTANT SAFETY INFORMATION

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm
Moderate to Severe Hepatic Impairment: Consider increased monitoring for bupivacaine systemic toxicity

*Primary endpoint.
†Median IV morphine mg equivalent.

48-Hour Data

Study 1: Did not achieve statistical significance of P=0.05 vs placebo³

11% Mean Reduction in Pain Intensity

XARACOLL: 179.3
Placebo: 201.3
P Value: 0.0568

64% Less Opioid Use^*

XARACOLL: 5 mg
Placebo: 14 mg
P Value: —

Study 2³

11% Mean Reduction in Pain Intensity

XARACOLL: 192.6
Placebo: 216.8
P Value: 0.0270

50% Less Opioid Use^*

XARACOLL: 10 mg
Placebo: 20 mg
P Value: 0.0003

*Median IV morphine mg equivalent.

72-Hour Opioid Data

PATIENTS REQUIRING NO OPIOIDS FROM 0 TO 72 HOURS

In two clinical studies, up to 36% of XARACOLL patients did not need opioids through 72 hours³*

*There was no statistically significant treatment effect for XARACOLL compared to placebo in Sum of Pain Intensity (SPI) at 72 hours and Total use of Opioid Analgesia (TOpA) at 72 hours.

Study 1

Patients NOT USING Opioids (%)

XARACOLL: 36^%
Placebo: 22^%

Study 2

Patients NOT USING Opioids (%)

XARACOLL: 28^%
Placebo: 12^%

Important Safety Information

CONTRAINDICATIONS

Known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of XARACOLL
Obstetrical paracervical block anesthesia. The use of bupivacaine in this technique has resulted in fetal bradycardia and death

WARNINGS AND PRECAUTIONS

Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient’s state of consciousness after placement of XARACOLL
Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use. See full Prescribing Information for more detail on managing these risks

ADVERSE REACTIONS

Most common adverse reactions in clinical trials (incidence ≥2% and higher than placebo) included incision site swelling, dysgeusia, headache, tremor, blurred vision, seroma, scrotal swelling, pyrexia, oral hypoaesthesia, and post procedural discharge.

To report SUSPECTED ADVERSE REACTIONS, contact Innocoll at 1-833-606-1421 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

Local Anesthetics: The toxic effects of local anesthetics are additive. Avoid additional local anesthetic administration within 96 hours following XARACOLL implantation. If additional local anesthetic administration with XARACOLL cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity.

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm
Moderate to Severe Hepatic Impairment: Consider increased monitoring for bupivacaine systemic toxicity

Please see full Prescribing Information.

References

1. Data on File. Innocoll Pharmaceuticals Limited. 2. Leiman D, Niebler G, Minkowitz H. Pharmacokinetics and safety of the bupivacaine collagen-matrix implant (INL-001) compared to liquid bupivacaine infiltration after open inguinal hernia repair. Poster presented at: World Congress on Regional Anesthesia & Pain Medicine; April 19-21, 2018; New York, NY. Accessed July 30, 2020. https://epostersonline.com/ASRAWORLD18/node/1154 3. Velanovich V, Rider P, Deck K, et al. Safety and efficacy of bupivacaine HCl collagen-matrix implant (INL-001) in open inguinal hernia repair: results from two randomized controlled trials. Adv Ther. 2019;36:200-216.

NEW XARACOLL® (bupivacaine HCl) implant

Significant Pain Relief You Can See

Study Design

24-Hour Efficacy

Study 1³

Study 2³

IMPORTANT SAFETY INFORMATION

48-Hour Data

Study 1: Did not achieve statistical significance of P=0.05 vs placebo³

Study 2³

72-Hour Opioid Data

Study 1

Study 2

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Indications and Usage

Limitations of Use

Important Safety Information

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

References

Significant Pain Relief You Can See

Study Design

24-Hour Efficacy

Study 13

Study 23

IMPORTANT SAFETY INFORMATION

48-Hour Data

Study 1: Did not achieve statistical significance of P=0.05 vs placebo3

Study 23

72-Hour Opioid Data

Study 1

Study 2

Request a Representative

Indications and Usage

Limitations of Use

Important Safety Information

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

References

Study 1³

Study 2³

Study 1: Did not achieve statistical significance of P=0.05 vs placebo³

Study 2³