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Trial record 51 of 728 for:    Area Under Curve AND Bioavailability

Bioavailability Study for New Atorvastatin Formulation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00844376
Recruitment Status : Completed
First Posted : February 16, 2009
Results First Posted : October 21, 2009
Last Update Posted : October 28, 2009
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label)
Condition Hypercholesterolemia
Interventions Drug: Atorvastatin suspension
Drug: Lipitor
Enrollment 12
Recruitment Details One center in the U.S.
Pre-assignment Details This study contained two sequences of 6 subjects per sequence. Each sequence received either test treatment followed by reference treatment, or reference treatment followed by test treatment. The order of administration was randomized to either of 2 sequences.
Arm/Group Title Test Drug First (Atorvastatin EP Suspension) Reference Drug First (Atorvastatin Tablet)
Hide Arm/Group Description 80-milligram (mg) Extemporaneous preparation (EP) suspension atorvastatin prototype formulation as a single dose in the first intervention period and commercial (reference) 80 mg atorvastatin tablet (Lipitor®) as a single dose in the second intervention period. Period 2 began immediately after period 1. 80-mg Commercial atorvastatin tablet (Lipitor®) as a single dose in the first intervention period and 80-mg EP suspension atorvastatin prototype formulation as a single dose in the second intervention period. Period 2 began immediately after period 1.
Period Title: Period 1: First Intervention
Started 6 6
Completed 5 6
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
Period Title: Period 2: Second Intervention
Started 5 6
Completed 5 [1] 6
Not Completed 0 0
[1]
Total subjects administered Test drug = 12; total subjects administered Reference drug = 11.
Arm/Group Title All Participants
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants
34.8  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
0
   0.0%
Male
12
 100.0%
1.Primary Outcome
Title Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48)
Hide Description Geometric means of AUC48 = area under the plasma concentration-time profile from time zero (0) to 48 hours postdose of atorvastatin (test versus [vs] reference); measured in nanograms times hour per milliliter (ng.hr/mL).
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Geometric Mean (Full Range)
Unit of Measure: ng.h/mL
135.05
(52.5 to 233.00)
140.79
(64.10 to 243.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test, Reference
Comments Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUC48; restricted (residual) maximum likelihood (REML) method of estimation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments The mixed effects model was implemented using SAS Proc Mixed, with REML estimation method and Kenward-Roger degrees of freedom algorithm.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 95.77
Confidence Interval 90%
85.82 to 106.88
Estimation Comments Natural log transformed AUC48 was analyzed using a mixed effect model with sequence, period and treatment as a fixed effect and subject within sequence as a random effect.
2.Primary Outcome
Title Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity)
Hide Description Geometric means of AUC infinity (AUCinf) = area under the plasma concentration-time curve from time zero (0) extrapolated to infinite time; measured in ng.hr/mL of atorvastatin (test vs reference).
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Geometric Mean (Full Range)
Unit of Measure: ng.hr/mL
135.88
(51.20 to 234.00)
142.86
(65.00 to 247.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test, Reference
Comments Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUCinf
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments The mixed effects model was implemented using SAS Proc Mixed, with REML estimation method and Kenward-Roger degrees of freedom algorithm.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 95.04
Confidence Interval 90%
84.99 to 106.27
Estimation Comments Natural log transformed AUCinf was analyzed using a mixed effect model with sequence, period and treatment as a fixed effect and subject within sequence as a random effect.
3.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description Geometric mean of Cmax = maximum observed plasma concentration of atorvastatin (test vs reference); measured in nanograms per milliliter (ng/mL).
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Geometric Mean (Full Range)
Unit of Measure: ng/mL
38.74
(20.30 to 86.80)
33.24
(16.60 to 52.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test, Reference
Comments Ratio of adjusted means (test/reference), and 90% CI for ratio--for Cmax
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments The mixed effects model was implemented using SAS Proc Mixed, with REML estimation method and Kenward-Roger degrees of freedom algorithm.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 117.90
Confidence Interval 90%
98.22 to 141.53
Estimation Comments Natural log transformed Cmax was analyzed using a mixed effect model with sequence, period and treatment as a fixed effect and subject within sequence as a random effect.
4.Secondary Outcome
Title Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast)
Hide Description Geometric mean of AUClast = area under the plasma concentration-time curve from time zero (0) to the last measurable concentration of atorvastatin (test vs reference); measured as ng.hr/mL
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Geometric Mean (Full Range)
Unit of Measure: ng.hr/mL
130.21
(45.50 to 231.00)
137.49
(56.00 to 243.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test, Reference
Comments Ratio of adjusted means (test/reference), and 90% CI for ratio--for AUClast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments The mixed effects model was implemented using SAS Proc Mixed, with REML estimation method and Kenward-Roger degrees of freedom algorithm.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 94.86
Confidence Interval 90%
83.86 to 107.29
Estimation Comments Natural log transformed AUClast was analyzed using a mixed effect model with sequence, period and treatment as a fixed effect and subject within sequence as a random effect.
5.Secondary Outcome
Title Terminal Phase Rate Constant (Kel)
Hide Description Geometric mean of Kel= termination phase rate constant for atorvastatin (test vs reference); measured as 1 per hour (1/hr).
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Geometric Mean (Full Range)
Unit of Measure: 1/hr
0.12
(0.09 to 0.26)
0.10
(0.06 to 0.15)
6.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax)
Hide Description Median of Tmax = time to maximum plasma concentration (Cmax) (test vs reference); measured in hours (hr).
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Median (Full Range)
Unit of Measure: hr
0.52
(0.50 to 2.00)
0.50
(0.50 to 3.00)
7.Secondary Outcome
Title Plasma Elimination Half-life (t1/2)
Hide Description Mean of t1/2 = terminal elimination half-life of atorvastatin (test vs reference); measured in hours.
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Test Reference
Hide Arm/Group Description:
80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation
80-mg Commercial atorvastatin tablet (Lipitor®)
Overall Number of Participants Analyzed 12 11
Mean (Standard Deviation)
Unit of Measure: hr
5.95  (1.40) 7.21  (2.23)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Test Reference
Hide Arm/Group Description 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation 80-mg Commercial atorvastatin tablet (Lipitor®)
All-Cause Mortality
Test Reference
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Test Reference
Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/11 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Test Reference
Affected / at Risk (%) Affected / at Risk (%)
Total   1/12 (8.33%)   1/11 (9.09%) 
Nervous system disorders     
headache  1  1/12 (8.33%)  1/11 (9.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.govCallCenter@pfizer.com
Layout table for additonal information
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00844376     History of Changes
Other Study ID Numbers: A2581164
First Submitted: February 13, 2009
First Posted: February 16, 2009
Results First Submitted: March 5, 2009
Results First Posted: October 21, 2009
Last Update Posted: October 28, 2009