Healthy
Conditions
Brief summary
This is a randomized, open-label study to evaluate the effect of a single dose of SSP-004184 on the pharmacokinetics of a single dose of simvastatin in healthy adult subjects.
Interventions
DRUGSimvastatin
DRUGSSP-004184SS
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal healthy male and female volunteers * Serum ferritin, hemoglobin and erythrocyte indices within normal range
Exclusion criteria
* Evidence of any active or chronic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) for Simvastatin | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours. | AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 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. |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Simvastatin | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours. | 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. |
| Maximum Plasma Concentration (Cmax) of Simvastatin | Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 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 |
|---|---|
| Simvastatin First Subjects received Simvastatin 20mg in Period 1, followed by Simvastatin 20mg and SSP-004184SS 30mg/kg during Period 2. | 15 |
| Simvastatin + SSP-004184SS First Subjects received Simvastatin 20mg and SSP-004184SS 30mg/kg in Period 1, followed by Simvastatin 20mg during Period 2. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Other | 0 | 1 |
Baseline characteristics
| Characteristic | Simvastatin First | Simvastatin + SSP-004184SS First | Total |
|---|---|---|---|
| Age, Continuous | 39.1 Years STANDARD_DEVIATION 14.97 | 39.6 Years STANDARD_DEVIATION 15.9 | 39.3 Years STANDARD_DEVIATION 15.17 |
| Age, Customized <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized Between 18 and 65 years | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment UNITED STATES | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 29 | 2 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Simvastatin
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: Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours.
Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Alone | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Simvastatin | 34.351 ng*h/ml | Standard Deviation 18.911 |
| Simvastatin + SSP-004184SS | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Simvastatin | 24.019 ng*h/ml | Standard Deviation 16.701 |
Comparison: The means of the log-transformed pharmacokinetic parameters were compared between treatments using a mixed-effects model with period and treatment as fixed effects, and subject nested within sequence as a random effect. In order to estimate the magnitude of the treatment regimen differences in pharmacokinetic parameters, the geometric mean ratio (i.e., the least squares mean difference in the log-transformed parameters back transformed to the original scale) and their 90% CIs were calculated.90% CI: [0.543, 0.73]Mixed-effects Model
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) for Simvastatin
AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 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: Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours.
Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Alone | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) for Simvastatin | 38.142 ng*h/ml | Standard Deviation 19.239 |
| Simvastatin + SSP-004184SS | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) for Simvastatin | 26.601 ng*h/ml | Standard Deviation 17.864 |
Comparison: The means of the log-transformed pharmacokinetic parameters were compared between treatments using a mixed-effects model with period and treatment as fixed effects, and subject nested within sequence as a random effect. In order to estimate the magnitude of the treatment regimen differences in pharmacokinetic parameters, the geometric mean ratio (i.e., the least squares mean difference in the log-transformed parameters back transformed to the original scale) and their 90% CIs were calculated.90% CI: [0.538, 0.744]Mixed-effects Model
Primary
Maximum Plasma Concentration (Cmax) of Simvastatin
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, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours.
Population: Pharmacokinetic Set: All subjects who took at least 1 dose of investigational product and for whom the primary pharmacokinetic data were considered sufficient and interpretable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simvastatin Alone | Maximum Plasma Concentration (Cmax) of Simvastatin | 5.006 ng/mL | Standard Deviation 3.125 |
| Simvastatin + SSP-004184SS | Maximum Plasma Concentration (Cmax) of Simvastatin | 2.72 ng/mL | Standard Deviation 1.265 |
Comparison: The means of the log-transformed pharmacokinetic parameters were compared between treatments using a mixed-effects model with period and treatment as fixed effects, and subject nested within sequence as a random effect. In order to estimate the magnitude of the treatment regimen differences in pharmacokinetic parameters, the geometric mean ratio (i.e., the least squares mean difference in the log-transformed parameters back transformed to the original scale) and their 90% CIs were calculated.90% CI: [0.526, 0.672]Mixed-effects Model