Healthy
Conditions
Brief summary
A Study to Evaluate the Pharmacokinetic Interaction Between SSP-004184 and Midazolam in Healthy Adult Subjects
Interventions
DRUGMidazolam
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 between the ages of 18 and 65, inclusive * 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) of Midazolam | Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 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 non-zero 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 Midazolam | Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 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 Midazolam | Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 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 |
|---|---|
| Midazolam First Subjects received Midazolam 6mg in Period 1, followed by Midazolam 6mg and SSP-004184SS 30mg/kg during Period 2. | 15 |
| Midazolam + SSP-004184SS First Subjects received Midazolam 6mg and SSP-004184SS 30mg/kg in Period 1, followed by Midazolam 6mg during Period 2. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Midazolam First | Midazolam + SSP-004184SS First | Total |
|---|---|---|---|
| Age, Continuous | 37 Years STANDARD_DEVIATION 10.45 | 44.9 Years STANDARD_DEVIATION 10.53 | 41 Years STANDARD_DEVIATION 11.07 |
| Age, Customized <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Between 18 and 65 years | 14 Participants | 15 Participants | 29 Participants |
| Region of Enrollment UNITED STATES | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 29 | 10 / 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 Midazolam
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 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 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 |
|---|---|---|---|
| Midazolam | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Midazolam | 100.935 ng*h/ml | Standard Deviation 54.014 |
| SSP-004184SS + Midazolam | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Midazolam | 116.902 ng*h/ml | Standard Deviation 37.45 |
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 AUClast, 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: [1.115, 1.327]Mixed-effects Model
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam
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 non-zero 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 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 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 |
|---|---|---|---|
| Midazolam | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam | 103.348 ng*hr/mL | Standard Deviation 54.087 |
| SSP-004184SS + Midazolam | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam | 120.1 ng*hr/mL | Standard Deviation 38.686 |
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 AUCinf, 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: [1.116, 1.323]Mixed-effects Model
Primary
Maximum Plasma Concentration (Cmax) of Midazolam
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 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 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 |
|---|---|---|---|
| Midazolam | Maximum Plasma Concentration (Cmax) of Midazolam | 35.124 ng/mL | Standard Deviation 12.532 |
| SSP-004184SS + Midazolam | Maximum Plasma Concentration (Cmax) of Midazolam | 48.29 ng/mL | Standard Deviation 12.605 |
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 Cmax, 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: [1.282, 1.491]Mixed-effects Model