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

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

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

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Propoxyphene napsylate (XP20C); Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: Placebo; 6 times a day in ascending doses until a maximum tolerated dose is identified
EXPERIMENTAL: 1	Drug: Propoxyphene napsylate (XP20C); 100 mg capsules 6 times a day in ascending doses until a maximum tolerated dose is identified; Other Names: propoxyphene napsylate; Darvon-N; XP20C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Xanodyne Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: May 24, 2010
• First Submitted That Met QC Criteria: May 27, 2010
• First Posted (ESTIMATE): May 31, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 13, 2011
• Last Update Submitted That Met QC Criteria: April 12, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Dextropropoxyphene; Levopropoxyphene
• Other Study ID Numbers: XP20C-101