Study of PHN131 in Patients After Surgery

Study Overview
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Brief Summary
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The purpose of this study is to assess the effectiveness, safety and pharmacokinetics of Oral Nalbuphine in the treatment of postoperative pain following hemorrhoidectomy.

Detailed Description
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• Primary Efficacy Endpoint: Pain assessment calculated as the area under the curve of VAS pain intensity scores through 48 hours. • Secondary Efficacy Endpoints: Consumption of diclofenac (Day 1-2) via Intramuscular Injection (IM injection). Time from the end of operation to the first IM injection diclofenac dose Brief Pain Inventory (BPI). Patient satisfaction.

Official Title
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A Randomized, Double Blind, Placebo-controlled, Multiple Dose Study to Assess the Efficacy, Safety and Pharmacokinetics of Oral Nalbuphine, an Oral Soft Capsule, for Post-hemorrhoidectomy Pain Management

Conditions
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Analgesia Disorder

Intervention / Treatment
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* Drug: PHN131 soft capsule with Nalbuphine HCl 60 mg/cap
* Drug: Placebo soft capsules
* Drug: Dicofenac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >= 20 years of age at Screening Scheduled to electively undergo 2 or 3-column excisional hemorrhoidectomy American Society of Anesthesiology Physical Class 1 - 3 Clinical lab values twice the upper limit of normal (values of potential clinical concern are detailed in Appendix) or, if abnormal, deemed not clinically significant per the Investigator. Ability and willingness to provide informed consent, adhere to the study visit schedule and complete all study assessments and language specific questionnaires. Exclusion Criteria: Body weight less than 40 kg. Concurrent fissurectomy. Subject is pregnant or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test at Baseline. Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, IUD, barrier device or abstinence) throughout the study. History of hypersensitivity or allergy to amide-type local anesthetics, opioid, or any ingredient of the medications administered in this study. Subject has a resting respiratory rate less than 8 per minute and blood oxygen saturation less than 90 mmHg. Use of any NSAIDs, selective COX-2 inhibitors, opioid, acetaminophen, selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA), gabapentin, or pregabalin within three days of surgery. Chronic use of opioid medications for more than 14 days in the last 3 months, or non-opioid pain medications more than 5 times per week. Use of any long-acting opioid medication within 3 days of surgery or any opioid medication within 24 hours of surgery. Current painful physical condition or concurrent surgery requires analgesic treatment in the postoperative period. Contraindication to epinephrine or any of the pain-control agents planned for postoperative use. Administration of an investigational drug within the longer of 30 days or 5 elimination half-lives of such investigational drug prior to study drug administration. Any psychiatric disorder, psychological, medical, or laboratory condition that may interfere with study assessments or compliance. Significant medical conditions or laboratory results that may indicate an increased vulnerability to study drugs and procedures, and thus expose the subject to an unreasonable risk as a result of participating in this clinical trial. Any clinically significant event or condition uncovered during surgery. History of abuse illicit drugs, prescription medicines or alcohol within the past 2 years. Known history of anti-HIV antibody positive . Failure to pass drug and alcohol screen.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Placebo soft capsules | Drug: Placebo soft capsules<br>* Multiple dose of oral Placebo soft capsules, initial dose: 2 capsules, then 1 capsule; t.i.d.<br>* Other names: Placebo;Drug: Dicofenac<br>* All subjects will receive diclofenac by IM injection for analgesia as rescue pain control.<br>|
| Experimental: Study group<br>PHN131 soft capsule with Nalbuphine HCl 60 mg/cap | Drug: PHN131 soft capsule with Nalbuphine HCl 60 mg/cap<br>* Multiple dose of oral PHN131 soft capsule with Nalbuphine HCl 60 mg/cap, initial dose : 120 mg ( 2 capsules), then 60 mg (1 capsule); t.i.d.<br>* Other names: PHN131;Drug: Dicofenac<br>* All subjects will receive diclofenac by IM injection for analgesia as rescue pain control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the area under the curve of VAS pain intensity scores | Pain assessment calculated as the area under the curve of VAS pain intensity scores through 48 hours | at 1, 2, 3, 4±0.25, 8±0.5, 12±0.5, 16±0.5, 20±0.5, 24±1, 28±1, 32±2, 36±2, 40±2, 44±2, and 48±2 h after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consumption of diclofenac dose | Consumption of diclofenac (Day 1-2) via Intramuscular Injection (IM injection) | in 48 hours after surgery | 
| Time of operation to diclofenac dose | Time from the end of operation to the first IM injection diclofenac dose | in 48 hours after surgery | 
| Brief Pain Inventory (BPI) | Brief Pain Inventory (BPI) | at 24h and 48h after surgery | 
| Patient satisfaction | Patient satisfaction | at 48h after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesic, Narcotics, Opioids, Pain relief after surgery