Novel Approaches for Quantitative Assessment of Adherence

Study Overview
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Brief Summary
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Approximately 12 adults subjects will be enrolled. Participants will be randomized to one of two directly observed dosing regimens with 2mg adenine 5+ (five stable-labeled nitrogens) as follows: 1 dose/week followed by 4 doses/week OR 3 doses/week followed by 7 doses/week. Each dose regimen will have a duration of approximately 12 weeks and will be separated by a 12-week washout period for a total study duration of approximately 36 weeks. Dried blood spots (DBS) and whole blood will be collect weekly. Urine will be collected less frequently, about every 2 weeks. The ratio of ATP 5+ to naturally occurring ATP 2+ is dried blood spots will be the primary outcome, as adenine is phosphorylated to ATP in red blood cells. Breakdown products will be measured in urine. Investigators will allow flexibility in terms of which days are used for dosing for the 1, 3, and 4 dose(s)/week regimens. This is scientifically justified as investigators expect a 20-30 day half-life of ATP 5+ in DBS.

Detailed Description
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Approximately twelve healthy adult volunteers with no contraindicated medical conditions or medications will be recruited from CU/Denver and the surrounding community. Participants will be randomized to one of 2 sequences consisting of two directly observed dosing regimens with 2mg adenine 5+ per dose, 1 dose/week followed by 4 doses/week or 3 doses/week followed by 7 doses/week. Each dose regimen will have a duration of approximately 12 weeks and will be separated by an approximately 12-week washout period for a total study duration of approximately 36 weeks. The rationale for this study design is several fold. First, the lower doses are given initially to minimize the potential effects of carry-over in the second regimen. Second, 1 to 7 doses/week encompass a wide range of simulated adherence rates to assess the promise of this taggant, adenine 5+, as an adherence biomarker. Third, the 12 week duration is designed to achieve  90% of steady-state given an estimated half-life of 20-30 days.

Official Title
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Novel Approaches for Quantitative Assessment of Adherence

Conditions
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Healthy

Intervention / Treatment
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* Other: Adenine 5+ (five stable-labeled nitrogens)


Participation Criteria
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Eligibility Criteria
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Ambulatory 18-40 year old adults. Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1 dose/week followed by 4 doses/week<br>Directly observed dosing regimen with 2 mg adenine 5+ (five stable-labeled nitrogens) as follows: 1 dose/week followed by 4 doses/week. The duration of each dosing regimen will be approximately 12 weeks. A washout period of approximately 12 weeks will separates the dosing regimens. | Other: Adenine 5+ (five stable-labeled nitrogens)<br>* taggant coencapsulated with an excipient<br>* Other names: taggant;|
| 3 doses/week followed by 7 doses/week.<br>Directly observed dosing regimen with 2 mg adenine 5+ (five stable-labeled nitrogens) as follows: 3 doses/week followed by 7 doses/week. The duration of each dosing regimen will be approximately 12 weeks. A washout period of approximately 12 weeks will separates the dosing regimens. | Other: Adenine 5+ (five stable-labeled nitrogens)<br>* taggant coencapsulated with an excipient<br>* Other names: taggant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of ATP 5+ to ATP 2+ in DBS | Ratio of ATP 5+ to ATP 2+ in DBS following directly observed therapy with 2mg of adenine 5+ at 1, 3, 4, and 7 doses/week | 9 months | 
| Dose-proportionality ATP 5+ to ATP 2+ in DBS | Dose-proportionality to relate ATP 5+ to ATP 2+ in DBS with adherence rate. | 9 months |