Healthy
Conditions
Brief summary
This study will evaluate the relative bioavailability of the new SSP-004184SS capsule formulation compared to the original SSP-004184AQ drug plus excipients formulation.
Interventions
DRUGSSP-004184AQ
Magnesium salt
DRUGSSP-004184SS
Disodium salt
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After One Dose | 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. | 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 |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After One Dose | 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. | 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. |
| Maximum Plasma Concentration (Cmax) of SSP-004184 After One Dose | 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. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After Two Doses | 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. | 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. |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After Two Doses | 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. | 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. |
| Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | 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. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AQ-SS-AQ2 SSP-004184AQ 40mg/kg as a single dose, followed by SSP-004184SS 21.8mg/kg as a single dose, followed by SSP-004184AQ 40mg/kg as a morning and evening dose. | 7 |
| AQ-SS-SS2 SSP-004184AQ 40mg/kg as a single dose, followed by SSP-004184SS 21.8mg/kg as a single dose, followed by SSP-004184SS 21.8mg/kg as a morning and evening dose. | 7 |
| SS-AQ-AQ2 SSP-004184SS 21.8mg/kg as a single dose, followed by SSP-004184AQ 40mg/kg as a single dose, followed by SSP-004184AQ 40mg/kg as a morning and evening dose. | 7 |
| SS-AQ-SS2 SSP-004184SS 21.8mg/kg as a single dose, followed by SSP-004184AQ 40mg/kg as a single dose, followed by SSP-004184SS 21.8mg/kg as a morning and evening dose. | 7 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 3 | Other | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | AQ-SS-AQ2 | AQ-SS-SS2 | SS-AQ-AQ2 | SS-AQ-SS2 |
|---|---|---|---|---|---|
| Age, Continuous | 43 Years STANDARD_DEVIATION 11.4 | 43.7 Years STANDARD_DEVIATION 12.58 | 44.4 Years STANDARD_DEVIATION 11.53 | 41.3 Years STANDARD_DEVIATION 10.27 | 42.7 Years STANDARD_DEVIATION 13.46 |
| Age, Customized >=65 years | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 65 years | 27 Participants | 6 Participants | 7 Participants | 7 Participants | 7 Participants |
| Region of Enrollment UNITED STATES | 28 Participants | 7 Participants | 7 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 7 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 21 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 28 | 11 / 28 | 5 / 12 | 5 / 13 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 12 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product, had at least 1 post-dose safety assessment, and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SSP-004184AQ (Single Dose) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After One Dose | 263911.3 ng*h/mL | Standard Deviation 68979.4 |
| SSP-004184SS (Single Dose) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After One Dose | 164614.8 ng*h/mL | Standard Deviation 43858.8 |
90% CI: [1.07, 1.422]
Primary
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
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product, had at least 1 post-dose safety assessment, and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SSP-004184AQ (Single Dose) | Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After One Dose | 261901.9 ng*h/mL | Standard Deviation 71252.3 |
| SSP-004184SS (Single Dose) | Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After One Dose | 164340 ng*h/mL | Standard Deviation 43914 |
90% CI: [1.081, 1.43]
Primary
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
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product, had at least 1 post-dose safety assessment, and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SSP-004184AQ (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After One Dose | 110114.3 ng/mL | Standard Deviation 26503 |
| SSP-004184SS (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After One Dose | 77068.6 ng/mL | Standard Deviation 21198.9 |
90% CI: [1.135, 1.592]
Secondary
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.
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product, had at least 1 post-dose safety assessment, and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SSP-004184AQ (Single Dose) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After Two Doses | 546114.1 ng*hr/mL | Standard Deviation 186698.2 |
| SSP-004184SS (Single Dose) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 After Two Doses | 294758.5 ng*hr/mL | Standard Deviation 81194.7 |
Secondary
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.
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product and had at least 1 post-dose safety assessment and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SSP-004184AQ (Single Dose) | Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After Two Doses | 545957 ng*hr/mL | Standard Deviation 186707.3 |
| SSP-004184SS (Single Dose) | Area Under the Steady-state Plasma Concentration-time Curve (AUClast) of SSP-004184 After Two Doses | 294186.8 ng*hr/mL | Standard Deviation 78102.1 |
Secondary
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.
Time frame: 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.
Population: Pharmacokinetic Set: All subjects who had taken at least 1 dose of investigational product, had at least 1 post-dose safety assessment, and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SSP-004184AQ (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | Dose 2 | 73776.9 ng/mL | Standard Deviation 17193.2 |
| SSP-004184AQ (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | Dose 1 | 112558.3 ng/mL | Standard Deviation 28036.8 |
| SSP-004184SS (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | Dose 2 | 43015.4 ng/mL | Standard Deviation 11168.8 |
| SSP-004184SS (Single Dose) | Maximum Plasma Concentration (Cmax) of SSP-004184 After Two Doses | Dose 1 | 77958.3 ng/mL | Standard Deviation 34372.5 |