Multiple-Ascending-Dose Study to Evaluate the Safety of Propoxyphene Napsylate In Healthy Adult Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine the daily maximum tolerated dose of propoxyphene napsylate in healthy subjects.

Official Title
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A Randomized, Multiple-Dose, Double-Blind, Placebo-Controlled Study of Sequential Ascending Dose Levels to Assess the Safety, Tolerability and Electrocardiographic Effects of Propoxyphene Napsylate Capsules (and Its Metabolite Norpropoxyphene) When Administered Orally to Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Propoxyphene napsylate (XP20C)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index ≥ 18 and ≤ 30 (kg/m2) Medically healthy with normal screening results, or in the case of results that are abnormal; the abnormal results are clinically insignificant (eg, medical history, physical examination, neurological assessment, vital signs, oxygen saturation, laboratory profiles) 12-lead ECGs (calculations by the electrocardiograph) which have no clinically significant findings Vital signs which are within normal range No tobacco/nicotine-containing product use for a minimum of 6 months If female, must be able to adhere to acceptable methods of contraception or be postmenopausal or surgically sterile Exclusion Criteria: History or presence of significant cardiovascular, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease History or presence of any degree of chronic obstructive pulmonary disease History of suicidal ideations or depression requiring professional intervention including counseling or antidepressant medication Any history of drug or alcohol abuse Positive drug (urine)/alcohol (breath) testing at screening or check-in Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) History of hypersensitivity or allergy to propoxyphene or any opioid compound, naloxone, naltrexone, palonosetron (Aloxi®), glycerin, senna, or bisacodyl (Dulcolax®) Use of any prescription medication (with the exception of hormonal contraceptives for females) within 2 weeks of enrollment Use of any over-the-counter medication, including herbal products, within 1 week of enrollment Use of any drugs known to significantly inhibit or induce liver enzymes involved in drug metabolism [CYP P450]) within 30 days of enrollment Blood donation or significant blood loss within 30 days of enrollment Plasma donation within 7 days of enrollment Participation in another clinical trial within 30 days of enrollment Females who are pregnant or lactating Any other condition or prior therapy, which, in the opinion of the PI, would make the subject unsuitable for this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Propoxyphene napsylate (XP20C)<br>* 100 mg capsules 6 times a day in ascending doses until a maximum tolerated dose is identified<br>* Other names: XP20C;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 6 times a day in ascending doses until a maximum tolerated dose is identified<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety and tolerability of propoxyphene napsylate as determined by evaluation of adverse events, change from baseline of ventricular repolarization, lab results, and mental status |  | Day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the relationship between serum concentrations of propoxyphene and norpropoxyphene on cardiac conduction and pharmacokinetic linearity of sequentially increased dose levels of propoxyphene napsylate. |  | Days -1, 1, 4, 11 |