Clinical trial NCT02194764: An Adherence Tool to Manage Narcotic -Addicted HIV Patients
Official title: A Breath-based Naltrexone Adherence Tool to Manage Narcotic-addicted HIV Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Adults
Lead sponsor: Xhale Assurance
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2014-07-18
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to develop a cost-effective breath-based medication adherence monitoring system that can monitor whether recovering opiate addicts actually take a specific treatment medication called naltrexone.

Detailed description: This study will have two parts. In the first part we will create eight SMART capsule-based naltrexone systems using 4 general types of pharma formulation strategies. Model naltrexone (50mg) formulations containing the GRAS taggant, 2-butanol (40 or 80 mg) will be prepared and preliminary stability studies executed. Type 1 is a hydrophobic system, Type 2 is a hydrophilic system, Type 3 is a reverse micelle system and Type 4 is a water-in-oil microemulsion system. All formulations will be prepared using USP-grade excipients, 2-butanol, naltrexone base and naltrexone HCl. Naltrexone HCl has significant water solubility and will be used in the preparation of formulation types 2 and 4, whereas the more lipid soluble free base of naltrexone will be used in formulation types 1 and 3. Manufacturer's specifications supplied by Capsugel will be used to determine compatibility between the capsule material and the proposed excipients, and will guide capsule selection (gelatin or HPMC).Prepared formulations will be characterized by particle size analysis and analyzed to determine the actual concentrations of naltrexone and 2-butanol. Particle sizing will be accomplished by dynamic light scattering using a 90Plus particle size analyzer. With formulation types 1 and 2, the technique will demonstrate the homogeneity of the mixture and the absence of particulates. With types 3 and 4, particle size distributions will be measured to confirm the presence of monodisperse reverse micelles or nanoscale droplets. The concentration of naltrexone in each final formulation will be verified by Liquid chromatography-mass spectrometry (LC-MS) and /or Ultra Performance Liquid Chromatography (UPLC). The concentration of 2-butanol will be determined by gas chromatography-Mass Spectrometry (GC-MS). Following the initial characterization, the formulations will be stored in sealed vials and placed in ICH standard stability conditions and tested at weekly intervals over 1, 3 and 6 months. The three outstanding formulation candidates will be selected to use in part two of the study.

In the second part the three formulations will be selected from those meeting the criteria for stability, solubility, particle size, color and concentration of 2-butanol in the first part of the study. Each of these formulations will be prepared by a certified pharmacy. In addition to the three selected naltrexone formulations, a fourth dosage form, a capsule-in-capsule (CIC) design, will be prepared in the pharmacy by incorporating 40 or 80 mg (determined from the first part of the study) of 2-butanol which is encapsulated (size 3 capsule) plus 50 mg of naltrexone (HCI form) in a size 0 double blind hard gel capsule. This capsule-in-capsule design will serve as a formulation-free positive control.

Note: All naltrexone formulations, which will be administered to human subjects, will contain quantities of excipients/components already designated by the FDA as being safe (e.g., inactive ingredient list, permissible daily exposure \[PDE\], GRAS/direct food additive designation).

Eligibility criteria: Inclusion Criteria:

* Ability to understand and provide written informed consent
* Subject is at least 18 Years of Age
* Subject must be willing to comply with study procedures

Exclusion Criteria:

* \<18 years
* Subject has a history of opioid use disorder
* current chronic opioid therapy or recent (past week) acute opioid therapy,
* currently pregnant
* contraindications to naltrexone use per FDA label.

Primary outcomes:
measure: Concentration of 2-butanol determined by gas chromatography mass spectroscopy (GC-MS)
timeFrame: Weekly intervals over 1, 3 and 6 months.
measure: breath concentration versus time
timeFrame: -5, 0, 5, 10, 20, 40, 60, 90 min
Secondary outcomes:
measure: Breath Pharmacokinetics (Cmax) of the Naltrexone Formulations
timeFrame: -5, 0, 5, 10, 20, 40, 60, 90
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: Xhale Smart, Inc.
name: Donn Dennis, M.D., F.A.H.A.
role: STUDY_DIRECTOR
References: