Healthy
Conditions
Brief summary
To assess the effect of food on the pharmacokinetic profile of SSP-004184 compared to administration under fasted conditions.
Interventions
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 inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the Screening Visit. * Subject is considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis. * Serum ferritin \>20ng/mL, hemoglobin \>125g/l, and erythrocyte indices within normal range of the clinical laboratory at the Screening Visit and on Day -1: packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration, or deemed not clinically significant by the investigator. * Subject is willing to comply with any applicable contraceptive requirements of the protocol and is: * Male, or * Female of non-childbearing potential (defined as a female who is post-menopausal \[amenorrhea for at least 12 consecutive months\] or surgically sterile \[hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy\]) and at least 6 weeks post-sterilization * Non-pregnant, non-lactating female * At least 90 days post-partum or nulliparous (females only). * An understanding, ability, and willingness to fully comply with study procedures and restrictions. * Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with International Conference on Harmonisation Good Clinical Practice Guideline E6 (1996) and applicable regulations, before completing any study-related procedures. * Body mass index between 18.5-30.0kg/m² inclusive. This inclusion criterion will be assessed only at the Screening Visit. * Ability to swallow the investigational product (multiple capsules at 1 time or consecutively 1 capsule at a time).
Exclusion criteria
* A clinically significant history or disorder detected during the medical interview/physical examination such as any cardiovascular, bronchopulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gall bladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator. * Confirmed systolic blood pressure \>139mmHg or \<89mmHg, and diastolic blood pressure \>89mmHg or \<49mmHg. * Twelve-lead ECG demonstrating QTc \>450msec at screening. If QTc exceeds 450msec, the ECG should be repeated 2 more times and the average of the 3 QTc values should be used to determine the subject's eligibility. * Subject reports any food allergies, celiac disease, or requirements for specific diet (eg, vegan, vegetarian, low fat). * 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. * History of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months of the Screening Visit. * History of alcohol or other substance abuse within the last year. * Routine consumption of more than 3 units of caffeine per day or subjects who experience caffeine withdrawal headaches. * A positive screen for alcohol or drugs of abuse at the Screening Visit. * 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 human immunodeficiency virus antibody screen, hepatitis B surface antigen screen, or hepatitis C virus antibody screen. * Current use of any other medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the study evaluations according to the investigator. * 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. * Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to Day 1 of Treatment Period 1. * Use of another investigational product within 30 days prior to Day 1 of Treatment Period 1 or active enrollment in another drug or vaccine clinical study. * Substantial changes in eating habits within 30 days prior to Day 1 of Treatment Period 1, as assessed by the investigator. * Prior screen failure, randomization, participation, or enrollment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours. | AUCinf is the area under the plasma concentration versus time curve from time 0 to infinity. 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 Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours. | AUClast is the area under the 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. |
| Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours. | 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 |
|---|---|
| SSP-004184SS Fed First Subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast in Treatment Period 1. During Treatment Period 2, subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions. | 5 |
| SSP-004184SS Fasted First Subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions on Day 1 in Treatment Period 1. During Treatment Period 2, subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | SSP-004184SS Fasted First | SSP-004184SS Fed First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 9 Participants |
| Age, Continuous | 35 Years STANDARD_DEVIATION 7.62 | 42 Years STANDARD_DEVIATION 10.89 | 38.9 Years STANDARD_DEVIATION 9.73 |
| Region of Enrollment UNITED STATES | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 9 | 4 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions
AUClast is the area under the 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: Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.
Population: Pharmacokinetic Set: All subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SSP-004184SS (Fed) | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions | 112,066.1 ng*hr/mL |
| SSP-004184SS (Fasted) | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions | 154,446 ng*hr/mL |
90% CI: [0.67, 0.769]
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions
AUCinf is the area under the plasma concentration versus time curve from time 0 to infinity. 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: Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.
Population: Pharmacokinetic Set: All subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SSP-004184SS (Fed) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions | 112,236.7 ng*hr/mL |
| SSP-004184SS (Fasted) | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions | 154,676.6 ng*hr/mL |
90% CI: [0.67, 0.77]
Primary
Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions
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: Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SSP-004184SS (Fed) | Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions | 32,755.6 ng/mL |
| SSP-004184SS (Fasted) | Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions | 70,733.3 ng/mL |
90% CI: [0.38, 0.53]