Pharmacokinetics Study of ALO-02 and OxyContin

Study Overview
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Brief Summary
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To characterize the single- and multiple-dose pharmacokinetics of oxycodone following the administration of ALO-02 40 Mg Twice Daily, ALO-02 80 Mg Once Daily or Oxycontin 40 Mg Twice Daily in Healthy Volunteers

Official Title
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An Open-label, Single-dose and Multiple-dose, Randomized, Crossover Study to Evaluate Pharmacokinetics, Safety and Tolerability After Administration of ALO-02 40 Mg Twice Daily Compared to ALO-02 80 Mg Once Daily and to Oxycontin 40 Mg Twice Daily in Healthy Volunteers

Conditions
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Management of Moderate to Severe Pain

Intervention / Treatment
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* Drug: ALO-02
* Drug: Naltrexone block
* Drug: ALO-02
* Drug: Naltrexone block
* Drug: OxyContin
* Drug: Naltrexone block


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Exclusion Criteria: Evidence or history of clinically significant diseases.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 mg ALO-02 capsule<br>Single- and multiple-dose of 40 mg ALO-02 capsule under 50 mg naltrexone block | Drug: ALO-02<br>* Day 1 (40 mg ALO-02 capsule, single dose) Days 2-5 (40 mg ALO-02 capsule, twice daily)<br>Drug: Naltrexone block<br>* Naltrexone Hcl 50 mg tablet will be administered (1) 12.5 hours prior to, 30 minutes prior to, and 11.5 hours after Day 1 dosing, (2) 30 minutes prior to each dose of study drug on Days 2-5 dosing, (3) 11.5 hours after Day 5 PM dosing<br>|
| Experimental: 80 mg ALO-02 capsule<br>Single- and multiple-dose of 80 mg ALO-02 capsule under 50 mg naltrexone block | Drug: ALO-02<br>* Day 1 (80 mg ALO-02 capsule, single dose) Days 2-5 (80 mg ALO-02 capsule, once daily)<br>Drug: Naltrexone block<br>* Naltrexone Hcl 50 mg tablet will be administered (1) 12.5 hours prior to, 30 minutes prior to, and 11.5 hours after Day 1 dosing, (2) 30 minutes prior to each dose and 11.5 hours after the AM dosing on Days 2-5, (3) 23.5 hours after Day 5 dosing.<br>|
| Experimental: 40 mg OxyContin tablet<br>Single- and multiple-dose of 40 mg OxyContin tablet under 50 mg naltrexone block | Drug: OxyContin<br>* Day 1 (40 mg OxyContin tablet, single dose) Days 2-5 (40 mg OxyContin tablet, twice daily)<br>Drug: Naltrexone block<br>* Naltrexone Hcl 50 mg tablet will be administered (1) 12.5 hours prior to, 30 minutes prior to, and 11.5 hours after Day 1 dosing, (2) 30 minutes prior to each dose of study drug on Days 2-5 dosing, (3) 11.5 hours after Day 5 PM dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-dose administration: Maximum Observed Plasma Concentration (Cmax) of oxycodone |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Area under the plasma concentration versus time curve from time zero to 24 hours (AUC24) of oxycodone |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Time to Reach Maximum Observed Plasma Concentration (Tmax) of oxycodone |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Multiple-dose administration: Area under the plasma concentration versus time curve from time zero to 24 hours (AUC24) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Area under the plasma concentration versus time curve within a dosing interval of τ at steady state (AUCτ) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Maximum plasma concentration at steady state on Day 5 (Cmax,ss) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Minimum plasma concentration at steady state on Day 5 (Cmin,ss) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Average plasma concentration at steady state on Day 5 (Cave,ss) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Time to Reach Maximum Observed Plasma Concentration on Day 5 (Tmax) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Plasma Decay Half-Life (t1/2) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Peak to trough fluctuation at steady state (PTF) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Accumulation ratio based on Area Under Curve (AUC) (Rac) of oxycodone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-dose administration: Dose normalized Maximum Observed Plasma Concentration (Cmax(dn)) of oxycodone, noroxycodone, and oxymorphone. |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Dose-normalized Area under the plasma concentration versus time curve from time zero to 24 hours (AUC24(dn)) of oxycodone, noroxycodone, and oxymorphone. |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Maximum Observed Plasma Concentration (Cmax) of noroxycodone and oxymorphone. |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Area under the plasma concentration versus time curve from time zero to 24 hours (AUC24) of noroxycodone and oxymorphone. |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Single-dose administration: Time to Reach Maximum Observed Plasma Concentration (Tmax) of noroxycodone and oxymorphone. |  | 0, 1, 2, 4, 6, 8, 12, 14, 16, and 24 hours post Day 1 dosing | 
| Multiple-dose administration: Accumulation ratio (Rac) of oxycodone, as data permit |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Maximum Observed Plasma Concentration (Cmax) of oxycodone, as data permit |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Area under the plasma concentration versus time curve from time zero to 24 hours (AUC24) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Area under the plasma concentration versus time curve within a dosing interval of τ (AUCτ) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Maximum plasma concentration at steady state (Cmax,ss) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Minimum plasma concentration at steady state (Cmin,ss) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Average plasma concentration at steady state (Cave,ss) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Time to Reach Maximum Observed Plasma Concentration (Tmax) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Plasma Decay Half-Life (t1/2) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Peak to trough fluctuation at steady state (PTF) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Rac of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 
| Multiple-dose administration: Maximum Observed Plasma Concentration (Cmax) of noroxycodone and oxymorphone, as data permit. |  | 96,96.5,97,98,100,102,104,108,108.5,109,110,112,114,116,120,132,144,168 hours post Day 1 dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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single- and multiple-dose pharmacokinetics, ALO-02, OxyContin