A Relative Bioavailability Study of SSP-004184AQ (Magnesium Salt) and SSP-004184SS (Disodium Salt)

Study Overview
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Brief Summary
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This study will evaluate the relative bioavailability of the new SSP-004184SS capsule formulation compared to the original SSP-004184AQ drug plus excipients formulation.

Official Title
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A Phase 1, Open-label, Randomized, 3-Period, Relative Bioavailability Study Comparing the Pharmacokinetics of SSP-004184AQ (Magnesium Salt) to SSP-004184SS (Disodium Salt) Each Administered as a Single Dose and as Two Doses of SSP-004184 (Free Acid) in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: SSP-004184AQ
* Drug: SSP-004184SS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Must be considered healthy. Serum ferritin >20ng/mL, hemoglobin >125g/L and erythrocyte indices within normal range Exclusion Criteria: Subject has a clinically significant history or a disorder detected during the medical interview/physical examination at the Screening Visit or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs Acute illness, as judged by the investigator, within 2 weeks of Day 1 of Treatment Period 1. Known or suspected intolerance or hypersensitivity to the investigational products, closely related compounds, or any of the stated ingredients. Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months History of alcohol or other substance abuse within the last year. A positive screen for alcohol or drugs of abuse at the Screening Visit. Confirmed systolic blood pressure >139mmHg or <89mmHg, and diastolic blood pressure >89mmHg or <49mmHg. Twelve-lead ECG demonstrating QTc >450msec at screening. Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day. A positive HIV antibody screen, HBsAg, or HCV antibody screen. Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch) within 30 days prior to Day 1 of Treatment Period 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSP-004184AQ (single dose)<br>40 mg/kg (oral capsule form) given once on Day 1 | Drug: SSP-004184AQ<br>* Magnesium salt<br>* Other names: SPD602;|
| Experimental: SSP-004184SS (single dose)<br>21.8 mg/kg (oral capsule form) given once on Day 1 | Drug: SSP-004184SS<br>* Disodium salt<br>* Other names: SPD602;|
| Experimental: SSP-004184AQ (2 doses)<br>40 mg/kg (oral capsule form) given twice (12 hours apart) on Day 1 | Drug: SSP-004184AQ<br>* Magnesium salt<br>* Other names: SPD602;|
| Experimental: SSP-004184SS (2 doses)<br>21.8 mg/kg (oral capsule form) given twice (12 hours apart) on Day 1 | Drug: SSP-004184SS<br>* Disodium salt<br>* Other names: SPD602;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After One Dose | AUC 0-last is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. | 
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After One Dose | AUCinf is the area under the curve extrapolated to infinity, calculated using the observed value of the last nonzero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. | 
| Maximum Plasma Concentration (Cmax) of SSP-004184 After One Dose | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After Two Doses | AUCinf is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last nonzero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. | 
| Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After Two Doses | AUClast is the area under the concentration versus time curve from the time of dosing to the last measurable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | Periods 1 & 2: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72, 96, and 120 hrs. Period 3: Within 30 min pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 12.5, 13, 13.5, 14, 14.5, 16, 20, 24, 48, 72, 96, and 120 hrs. |