Effect of SSP-004184 (SPD602) on the Pharmacokinetics of Simvastatin in Healthy Adult Subjects
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Simvastatin Administered as a single oral 20 mg dose on Day 1. |
Drug: Simvastatin
|
Experimental: Simvastatin + SSP-004184SS Simvastatin (20 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1. |
Drug: Simvastatin
Drug: SSP-004184SS
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinical Pharmacology of Miami, Inc. | Miami | Florida | United States |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SPD602-114
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Simvastatin First | Simvastatin + SSP-004184SS First |
---|---|---|
Arm/Group Description | Subjects received Simvastatin 20mg in Period 1, followed by Simvastatin 20mg and SSP-004184SS 30mg/kg during Period 2. | Subjects received Simvastatin 20mg and SSP-004184SS 30mg/kg in Period 1, followed by Simvastatin 20mg during Period 2. |
Period Title: Period 1 | ||
STARTED | 15 | 15 |
COMPLETED | 15 | 15 |
NOT COMPLETED | 0 | 0 |
Period Title: Period 1 | ||
STARTED | 15 | 15 |
COMPLETED | 15 | 14 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Simvastatin First | Simvastatin + SSP-004184SS First | Total |
---|---|---|---|
Arm/Group Description | Subjects received Simvastatin 20mg in Period 1, followed by Simvastatin 20mg and SSP-004184SS 30mg/kg during Period 2. | Subjects received Simvastatin 20mg and SSP-004184SS 30mg/kg in Period 1, followed by Simvastatin 20mg during Period 2. | Total of all reporting groups |
Overall Participants | 15 | 15 | 30 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
39.1
(14.97)
|
39.6
(15.9)
|
39.3
(15.17)
|
Age, Customized (Count of Participants) | |||
<=18 years |
0
0%
|
1
6.7%
|
1
3.3%
|
Between 18 and 65 years |
15
100%
|
14
93.3%
|
29
96.7%
|
Sex: Female, Male (Count of Participants) | |||
Female |
8
53.3%
|
9
60%
|
17
56.7%
|
Male |
7
46.7%
|
6
40%
|
13
43.3%
|
Region of Enrollment (Count of Participants) | |||
UNITED STATES |
15
100%
|
15
100%
|
30
100%
|
Outcome Measures
Title | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) for Simvastatin |
---|---|
Description | 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. |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Simvastatin Alone | Simvastatin + SSP-004184SS |
---|---|---|
Arm/Group Description | Administered as a single oral 20 mg dose on Day 1. | Simvastatin (20 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1. |
Measure Participants | 27 | 29 |
Mean (Standard Deviation) [ng*h/ml] |
38.142
(19.239)
|
26.601
(17.864)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Simvastatin Alone, Simvastatin + SSP-004184SS |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | If the 90% CI of the geometric mean ratios fell within the range (0.80, 1.25), then equivalence was assumed and the hypothesis that a drug interaction occurred was rejected. If the 90% CIs were not wholly contained within the range (0.80, 1.25), then a drug interaction was not excluded. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Means |
Estimated Value | 0.632 | |
Confidence Interval |
(2-Sided) 90% 0.538 to 0.744 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Simvastatin |
---|---|
Description | 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. |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Simvastatin Alone | Simvastatin + SSP-004184SS |
---|---|---|
Arm/Group Description | Administered as a single oral 20 mg dose on Day 1. | Simvastatin (20 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1. |
Measure Participants | 29 | 30 |
Mean (Standard Deviation) [ng*h/ml] |
34.351
(18.911)
|
24.019
(16.701)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Simvastatin Alone, Simvastatin + SSP-004184SS |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | If the 90% CI of the geometric mean ratios fell within the range (0.80, 1.25), then equivalence was assumed and the hypothesis that a drug interaction occurred was rejected. If the 90% CIs were not wholly contained within the range (0.80, 1.25), then a drug interaction was not excluded. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Means |
Estimated Value | 0.630 | |
Confidence Interval |
(2-Sided) 90% 0.543 to 0.730 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Maximum Plasma Concentration (Cmax) of Simvastatin |
---|---|
Description | 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. |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Simvastatin Alone | Simvastatin + SSP-004184SS |
---|---|---|
Arm/Group Description | Administered as a single oral 20 mg dose on Day 1. | Simvastatin (20 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1. |
Measure Participants | 29 | 30 |
Mean (Standard Deviation) [ng/mL] |
5.006
(3.125)
|
2.72
(1.265)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Simvastatin Alone, Simvastatin + SSP-004184SS |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | If the 90% CI of the geometric mean ratios fell within the range (0.80, 1.25), then equivalence was assumed and the hypothesis that a drug interaction occurred was rejected. If the 90% CIs were not wholly contained within the range (0.80, 1.25), then a drug interaction was not excluded. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Means |
Estimated Value | 0.594 | |
Confidence Interval |
(2-Sided) 90% 0.526 to 0.672 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Simvastatin Alone | Simvastatin + SSP-004184SS | ||
Arm/Group Description | Administered as a single oral 20 mg dose on Day 1. | Simvastatin (20 mg) + SSP-004184SS (30 mg/kg) administered concomitantly as a single oral dose on Day 1. | ||
All Cause Mortality |
||||
Simvastatin Alone | Simvastatin + SSP-004184SS | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Simvastatin Alone | Simvastatin + SSP-004184SS | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/29 (0%) | 0/30 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Simvastatin Alone | Simvastatin + SSP-004184SS | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/29 (3.4%) | 2/30 (6.7%) | ||
Nervous system disorders | ||||
Headache | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Shire |
Phone | +1 866 842 5335 |
ClinicalTransparency@shire.com |
- SPD602-114