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Bioequivalence Study Comparing A New 10 Mg Atorvastatin Tablet To A 10 Mg Atorvastatin Commercial Tablet

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ClinicalTrials.gov Identifier: NCT00917579
Recruitment Status : Completed
First Posted : June 10, 2009
Results First Posted : October 14, 2009
Last Update Posted : March 12, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Hypercholesterolemia
Intervention Drug: Atorvastatin
Enrollment 76
Recruitment Details Healthy volunteers were recruited from one research center between July 2008 and September 2008.
Pre-assignment Details  
Arm/Group Title Test Drug First, Then Reference Drug Reference Drug First, Then Test Drug
Hide Arm/Group Description New (test) 10 milligram (mg) atorvastatin tablet as a single oral dose in the first intervention period, and marketed (reference) 10 mg atorvastatin tablet as a single oral dose in the second intervention period (after washout period). Marketed (reference) 10 mg atorvastatin commercial tablet (Lipitor®) as a single oral dose in the first intervention period, and new (test) 10 mg atorvastatin tablet as a single oral dose in the second intervention period (after washout period).
Period Title: Period 1: 1st Intervention
Started 39 37
Completed 39 37
Not Completed 0 0
Period Title: Washout >= 2 Weeks
Started 39 37
Completed 37 37
Not Completed 2 0
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             1             0
Period Title: Period 2: 2nd Intervention
Started 37 37
Completed 37 37
Not Completed 0 0
Arm/Group Title Total Number of Participants
Hide Arm/Group Description All participants received atorvastatin 10 mg tablets (new and marketed).
Overall Number of Baseline Participants 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 76 participants
18-44 years 59
45-64 years 17
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Female
38
  50.0%
Male
38
  50.0%
1.Primary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Infinity)
Hide Description AUCinf = Area under the plasma concentration-time curve from time 0 (predose) extrapolated to infinite time; measured in nanograms times hour per milliliter (ng•hr/mL).
Time Frame 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Only 73 subjects contributed to the PK analysis in the reference group as plasma concentrations for 1 subject were below the limit of quantification, except 1 time point.
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description:
New (test) 10 mg atorvastatin tablet as a single oral dose in either first intervention period or second intervention period.
Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single oral dose in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 76 73
Mean (Standard Deviation)
Unit of Measure: ng•hr/mL
18.3206  (8.26454) 19.2583  (8.79739)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Drug, Reference Drug
Comments Natural log transformed AUCinf was analyzed using a mixed effects model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Adjusted mean difference (Test-Ref) and 90% CI was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean and 90% CI for the ratio. Alternative hypothesis of bioequivalence: (H1: θL <=µT - µR <=θU); null hypothesis of inequivalence: (Ho: µT - µR <θL or µT - µR >θU).
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Bioequivalence of the two treatments was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCinf and Cmax fell within (80%, 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Values were back-transformed from the log scale.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 95.34
Confidence Interval 90%
91.33 to 99.52
Estimation Comments Parameter estimate = ratio (%) (test/reference) of adjusted geometric means. AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
2.Primary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Hide Description AUClast = area under the plasma concentration-time curve from 0 (predose) to the time of the last measureable concentration (Clast); measured in nanograms times hour per milliliter (ng•hr/mL).
Time Frame 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population: all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Only 73 subjects contributed to the PK analysis in the reference group as plasma concentrations for 1 subject were below the limit of quantification, with the exception of 1 time point.
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description:
New (test) 10 mg atorvastatin tablet as a single oral dose in either first intervention period or second intervention period.
Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single oral dose in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 76 73
Mean (Standard Deviation)
Unit of Measure: ng•hr/mL
15.7382  (7.88920) 16.5452  (8.71551)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Drug, Reference Drug
Comments Natural log transformed AUClast was analyzed using a mixed effects model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence interval was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean (Test/Reference) and 90% confidence interval for the ratio.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Bioequivalence of the two treatments was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both the AUCinf and Cmax fell within (80%, 125%). AUCinf method of determination includes AUC last calculated value.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Values have been back-transformed from the log scale.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 95.79
Confidence Interval 90%
91.07 to 100.76
Estimation Comments Parameter estimate = ratio (%) (test/reference) of adjusted geometric means. Log-linear trapezoidal method.
3.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description Cmax = maximum observed plasma concentration. Measured in nanograms per milliter (ng/mL).
Time Frame 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population: all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Only 73 subjects contributed to the PK analysis in the reference group as plasma concentrations for 1 subject were below the limit of quantification, with the exception of 1 time point.
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description:
New (test) 10 mg atorvastatin tablet as a single oral dose in either first intervention period or second intervention period.
Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single oral dose in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 76 73
Mean (Standard Deviation)
Unit of Measure: ng/mL
2.6594  (1.44617) 2.8086  (1.23048)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Drug, Reference Drug
Comments Natural log transformed Cmax was analyzed using a mixed effects model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals were obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean (Test/Reference) and 90% confidence interval for the ratio.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Bioequivalence of the two treatments was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCinf and Cmax fell within (80%, 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Values have been back-transformed from the log scale.
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 91.41
Confidence Interval 90%
83.39 to 100.20
Estimation Comments Parameter estimate = ratio (%) (test/reference) of adjusted geometric means.
4.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax)
Hide Description Tmax = time (hours) to maximum plasma concentration (Cmax).
Time Frame 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population: all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Only 73 subjects contributed to the PK analysis in the reference group as plasma concentrations for 1 subject were below the limit of quantification, with the exception of 1 time point.
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description:
New (test) 10 mg atorvastatin tablet as a single oral dose in either first intervention period or second intervention period.
Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single oral dose in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 76 73
Median (Inter-Quartile Range)
Unit of Measure: hours
1.000
(0.250 to 9.000)
0.5000
(0.250 to 4.000)
5.Secondary Outcome
Title Plasma Elimination Half-life (t1/2)
Hide Description t1/2 = terminal elimination half-life in hours.
Time Frame 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population: all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Only 73 subjects contributed to the PK analysis in the reference group as plasma concentrations for 1 subject were below the limit of quantification, with the exception of 1 time point.
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description:
New (test) 10 mg atorvastatin tablet as a single oral dose in either first intervention period or second intervention period.
Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single oral dose in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 76 73
Mean (Standard Deviation)
Unit of Measure: hours
10.39  (4.0018) 10.78  (3.9640)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Test Drug Reference Drug
Hide Arm/Group Description New (test) 10 mg atorvastatin tablet as a single oral dose. Marketed (reference) 10 mg atorvastatin tablet (Lipitor®) as a single dose.
All-Cause Mortality
Test Drug Reference Drug
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Test Drug Reference Drug
Affected / at Risk (%) Affected / at Risk (%)
Total   1   0 
Renal and urinary disorders     
Renal colic  1  1/76 (1.32%)  0/74 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Test Drug Reference Drug
Affected / at Risk (%) Affected / at Risk (%)
Total   4   15 
Gastrointestinal disorders     
Constipation  1  1/76 (1.32%)  4/74 (5.41%) 
Dyspepsia  1  0/76 (0.00%)  1/74 (1.35%) 
Nausea  1  0/76 (0.00%)  2/74 (2.70%) 
Vomiting  1  0/76 (0.00%)  1/74 (1.35%) 
Nervous system disorders     
Dizziness  1  1/76 (1.32%)  1/74 (1.35%) 
Headache  1  1/76 (1.32%)  6/74 (8.11%) 
Syncope  1  0/76 (0.00%)  1/74 (1.35%) 
Syncope vasovagal  1  0/76 (0.00%)  2/74 (2.70%) 
Psychiatric disorders     
Anxiety  1  0/76 (0.00%)  1/74 (1.35%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  0/76 (0.00%)  1/74 (1.35%) 
Pharyngolaryngeal pain  1  0/76 (0.00%)  2/74 (2.70%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/76 (1.32%)  1/74 (1.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
ClinicalTrials.gov Identifier: NCT00917579    
Other Study ID Numbers: A2581166
First Submitted: June 8, 2009
First Posted: June 10, 2009
Results First Submitted: September 10, 2009
Results First Posted: October 14, 2009
Last Update Posted: March 12, 2021