Bioequivalence Study Comparing A New 80 Mg Atorvastatin Tablet To A 80 Mg Atorvastatin Commercial Tablet
Study Details
Study Description
Brief Summary
To determine whether new 80 mg atorvastatin tablets are bioequivalent to 80 mg commercial atorvastatin tablets (Lipitor®).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: Reference 80 mg atorvastatin tablets |
Drug: Atorvastatin
A single 80 mg dose of marketed 80 mg atorvastatin tablets
|
Experimental: Test New 80 mg atorvastatin tablets |
Genetic: Atorvastatin
A single dose of new formulation of 80 mg atorvastatin tablets
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Infinity) [0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose]
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). Pharmacokinetic (PK) parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose]
AUClast = area under the plasma concentration-time curve from 0 (predose) to the time of the last measureable concentration (Clast). PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4.
- Maximum Observed Plasma Concentration (Cmax) [0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose]
Cmax = maximum observed plasma concentration. Measured in nanograms per milliter (ng/mL); collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4.
Secondary Outcome Measures
- Time to Reach Maximum Plasma Concentration (Tmax) [0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose]
Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence; PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4.
- Plasma Elimination Half-life (t1/2) [0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose]
t1/2 = terminal elimination half-life in hours; ln 2/kel, where kel is the termination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy male and/or female subjects between the ages of 18 and 55 years.
-
Body Mass Index (BMI) of 18 to 30 kg/m2; and a total body weight >50 kg (110 lbs).
Exclusion Criteria:
-
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at screening.
-
Treatment with an investigational drug within 30 days or 5 half lives preceding the first dose of study medication.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Pfizer Investigational Site | Miami | Florida | United States | 33169 |
Sponsors and Collaborators
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A2581167
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Test Drug First | Reference Drug First |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period and marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the second intervention period (after washout period). | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period and new (test) 80 mg atorvastatin tablets as a single dose in the second intervention period (after washout period). |
Period Title: Period 1: First Intervention | ||
STARTED | 39 | 37 |
COMPLETED | 39 | 37 |
NOT COMPLETED | 0 | 0 |
Period Title: Period 1: First Intervention | ||
STARTED | 39 | 37 |
COMPLETED | 37 | 37 |
NOT COMPLETED | 2 | 0 |
Period Title: Period 1: First Intervention | ||
STARTED | 37 | 37 |
COMPLETED | 36 | 37 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Total Study Population |
---|---|
Arm/Group Description | New 80 milligram (mg) atorvastatin tablets (test); marketed 80 mg atorvastatin commercial tablet (Lipitor®) (reference) |
Overall Participants | 76 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
41.0
(9.0)
|
Sex: Female, Male (Count of Participants) | |
Female |
35
46.1%
|
Male |
41
53.9%
|
Outcome Measures
Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Infinity) |
---|---|
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). Pharmacokinetic (PK) parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4. |
Time Frame | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose |
Outcome Measure Data
Analysis Population Description |
---|
PK parameter analysis population defined as all subjects randomized and treated who had > = 1 of the parameters of primary interest in > = 1 treatment period. |
Arm/Group Title | Test Drug | Reference Drug |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. |
Measure Participants | 76 | 74 |
Mean (Standard Deviation) [ng*hr/mL] |
168.1355
(100.77765)
|
176.1731
(120.18642)
|
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 wholly within (80%, 125%) | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
Estimated Value | 98.79 | |
Confidence Interval |
() 90% 94.57 to 103.20 |
|
Parameter Dispersion |
Type: Value: |
|
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. |
Title | Time to Reach Maximum Plasma Concentration (Tmax) |
---|---|
Description | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence; PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4. |
Time Frame | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose |
Outcome Measure Data
Analysis Population Description |
---|
PK parameter analysis population |
Arm/Group Title | Test Drug | Reference Drug |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. |
Measure Participants | 76 | 74 |
Median (Full Range) [hours] |
1.0
|
1.0
|
Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
---|---|
Description | AUClast = area under the plasma concentration-time curve from 0 (predose) to the time of the last measureable concentration (Clast). PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4. |
Time Frame | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose |
Outcome Measure Data
Analysis Population Description |
---|
PK parameter analysis population |
Arm/Group Title | Test Drug | Reference Drug |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. |
Measure Participants | 76 | 74 |
Mean (Standard Deviation) [ng*hr/mL] |
162.5073
(100.56590)
|
170.4735
(119.70585)
|
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 AUCinf and Cmax fell wholly within (80%, 125%). AUCinf method of determination includes AUClast calculated value. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
Estimated Value | 98.72 | |
Confidence Interval |
() 90% 94.41 to 103.23 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Parameter estimate = ratio (%) (test/reference) of adjusted geometric means. Log-linear trapezoidal method. |
Title | Maximum Observed Plasma Concentration (Cmax) |
---|---|
Description | Cmax = maximum observed plasma concentration. Measured in nanograms per milliter (ng/mL); collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4. |
Time Frame | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose |
Outcome Measure Data
Analysis Population Description |
---|
PK parameter analysis population |
Arm/Group Title | Test Drug | Reference Drug |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. |
Measure Participants | 76 | 74 |
Mean (Standard Deviation) [ng/mL] |
43.1782
(31.70609)
|
43.0534
(36.47166)
|
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 wholly within (80%, 125%) | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
Estimated Value | 104.66 | |
Confidence Interval |
() 90% 95.73 to 114.42 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Parameter estimate = ratio (%) (test/reference) of adjusted geometric means. Observed directly from data. |
Title | Plasma Elimination Half-life (t1/2) |
---|---|
Description | t1/2 = terminal elimination half-life in hours; ln 2/kel, where kel is the termination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. PK parameters derived from subject's concentration data; collected Period 1, Day 1 to Day 4; Period 2, Day 1 to Day 4. |
Time Frame | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 10, 12, 24, 36, 48, 72 hours post dose |
Outcome Measure Data
Analysis Population Description |
---|
PK parameter analysis population |
Arm/Group Title | Test Drug | Reference Drug |
---|---|---|
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. |
Measure Participants | 76 | 74 |
Mean (Standard Deviation) [hours] |
9.330
(3.1792)
|
9.444
(4.0157)
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Test Drug | Reference Drug | ||
Arm/Group Description | New (test) 80 milligram (mg) atorvastatin tablets as a single dose in the first intervention period or second intervention period. | Marketed (reference) 80 mg atorvastatin commercial tablet (Lipitor®) as a single dose in the first intervention period or second intervention period. | ||
All Cause Mortality |
||||
Test Drug | Reference Drug | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Test Drug | Reference Drug | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/76 (0%) | 0/74 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Test Drug | Reference Drug | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/76 (14.5%) | 4/74 (5.4%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 1/76 (1.3%) | 0/74 (0%) | ||
Nausea | 1/76 (1.3%) | 0/74 (0%) | ||
Toothache | 1/76 (1.3%) | 0/74 (0%) | ||
Vomiting | 1/76 (1.3%) | 0/74 (0%) | ||
General disorders | ||||
Fatigue | 0/76 (0%) | 1/74 (1.4%) | ||
Infections and infestations | ||||
Dermatophytosis | 1/76 (1.3%) | 0/74 (0%) | ||
Nasopharyngitis | 1/76 (1.3%) | 0/74 (0%) | ||
Nervous system disorders | ||||
Headache | 6/76 (7.9%) | 3/74 (4.1%) | ||
Paraesthesia | 1/76 (1.3%) | 0/74 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Rash | 1/76 (1.3%) | 0/74 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Name/Title | Pfizer ClinicalTrials.gov Call Center |
---|---|
Organization | Pfizer, Inc. |
Phone | 1-800-718-1021 |
ClinicalTrials.govCallCenter@pfizer.com |
- A2581167