Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Comparing Drug Availability Of Methylprednisolone In Liquid Form Versus Methylprednisolone In Tablet Form

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: NCT01267201
Recruitment Status : Completed
First Posted : December 28, 2010
Results First Posted : June 28, 2012
Last Update Posted : June 28, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Biological Availability
Intervention Drug: methylprednisolone
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Methylprednisolone 32 mg Tablet, Formulation 1, Formulation 2 Methylprednisolone 32 mg Tablet, Formulation 2, Formulation 1 Methylprednisolone Formulation 1, 32 mg Tablet, Formulation 2 Methylprednisolone Formulation 1, Formulation 2, 32 mg Tablet Methylprednisolone Formulation 2, 32 mg Tablet, Formulation 1 Methylprednisolone Formulation 2, Formulation 1, 32 mg Tablet
Hide Arm/Group Description Single oral dose of methylprednisolone 32 milligram (mg) tablet on Day 1 in first intervention period; followed by single dose of formulation 1: methylprednisolone oral suspension 4 milligram/milliliter (mg/mL) at 32 mg (Micronized active pharmaceutical ingredient [API]) on Day 1 in second intervention period; and single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period. Single oral dose of methylprednisolone 32 mg tablet on Day 1 in first intervention period; followed by single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in second intervention period; and single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period. Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 in first intervention period; followed by single oral dose of methylprednisolone 32 mg tablet on Day 1 in second intervention period; and single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period. Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 in first intervention period; followed by single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in second intervention period; and single oral dose of methylprednisolone 32 mg tablet on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period. Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in first intervention period; followed by single oral dose of methylprednisolone 32 mg tablet on Day 1 in second intervention period; and single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period. Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 in first intervention period; followed by single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 in second intervention period; and single oral dose of methylprednisolone 32 mg tablet on Day 1 in third intervention period. A washout period of at least 2 days was maintained between each intervention period.
Period Title: First Intervention Period
Started 4 4 4 4 4 4
Completed 3 4 4 4 4 4
Not Completed 1 0 0 0 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0             0             0             0
Period Title: Washout Period (At Least 2 Days)
Started 3 4 4 4 4 4
Completed 3 4 4 4 4 4
Not Completed 0 0 0 0 0 0
Period Title: Second Intervention Period
Started 3 4 4 4 4 4
Completed 3 3 4 4 4 4
Not Completed 0 1 0 0 0 0
Reason Not Completed
Withdrawal by Subject             0             1             0             0             0             0
Period Title: Washout Period (At Least 2 Days)
Started 3 3 4 4 4 4
Completed 3 3 4 4 4 4
Not Completed 0 0 0 0 0 0
Period Title: Third Intervention Period
Started 3 3 4 4 4 4
Completed 3 3 4 4 4 4
Not Completed 0 0 0 0 0 0
Arm/Group Title Entire Study Population
Hide Arm/Group Description Includes all participants randomized to receive methylprednisolone 32 mg tablet first, formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) first and formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) first.
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
32.5  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
2
   8.3%
Male
22
  91.7%
1.Primary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Hide Description AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hours (hrs) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
Arm/Group Title Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Hide Arm/Group Description:
Single oral dose of methylprednisolone 32 mg tablet on Day 1 of any of the three intervention periods.
Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 of any of the three intervention periods.
Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 of any of the three intervention periods.
Overall Number of Participants Analyzed 24 22 23
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
1286.00  (385.27) 1204.00  (394.65) 1180.00  (355.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methylprednisolone 32 mg Tablet, Methylprednisolone 32 mg Micronized API
Comments Natural log transformed AUC (0 - ∞) of methylprednisolone was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 92.11
Confidence Interval (2-Sided) 90%
88.23 to 96.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methylprednisolone 32 mg Tablet, Methylprednisolone 32 mg Sieve Cut API
Comments Natural log transformed AUC (0 - ∞) of methylprednisolone was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 90.22
Confidence Interval (2-Sided) 90%
86.49 to 94.11
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
Arm/Group Title Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Hide Arm/Group Description:
Single oral dose of methylprednisolone 32 mg tablet on Day 1 of any of the three intervention periods.
Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 of any of the three intervention periods.
Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 of any of the three intervention periods.
Overall Number of Participants Analyzed 24 22 23
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
289.00  (60.42) 279.10  (82.91) 246.20  (66.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methylprednisolone 32 mg Tablet, Methylprednisolone 32 mg Micronized API
Comments Natural log transformed Cmax of methylprednisolone was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 94.76
Confidence Interval (2-Sided) 90%
88.06 to 101.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Methylprednisolone 32 mg Tablet, Methylprednisolone 32 mg Sieve Cut API
Comments Natural log transformed Cmax of methylprednisolone was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 83.89
Confidence Interval (2-Sided) 90%
78.06 to 90.17
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
Arm/Group Title Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Hide Arm/Group Description:
Single oral dose of methylprednisolone 32 mg tablet on Day 1 of any of the three intervention periods.
Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 of any of the three intervention periods.
Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 of any of the three intervention periods.
Overall Number of Participants Analyzed 24 22 23
Median (Full Range)
Unit of Measure: hr
2.00
(1.00 to 4.00)
1.00
(0.50 to 4.00)
2.00
(1.00 to 3.00)
4.Secondary Outcome
Title Plasma Decay Half-life (t1/2)
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all randomized participants who were treated and had at least 1 of the PK parameters of interest in at least 1 treatment period.
Arm/Group Title Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Hide Arm/Group Description:
Single oral dose of methylprednisolone 32 mg tablet on Day 1 of any of the three intervention periods.
Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 of any of the three intervention periods.
Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 of any of the three intervention periods.
Overall Number of Participants Analyzed 24 22 23
Mean (Standard Deviation)
Unit of Measure: hr
2.43  (0.39) 2.42  (0.37) 2.45  (0.35)
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Hide Arm/Group Description Single oral dose of methylprednisolone 32 mg tablet on Day 1 of any of the three intervention periods. Single dose of formulation 1: methylprednisolone oral suspension 4 mg/mL at 32 mg (Micronized API) on Day 1 of any of the three intervention periods. Single dose of formulation 2: methylprednisolone oral suspension 4 mg/mL at 32 mg (Sieve cut API) on Day 1 of any of the three intervention periods.
All-Cause Mortality
Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/22 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Methylprednisolone 32 mg Tablet Methylprednisolone 32 mg Micronized API Methylprednisolone 32 mg Sieve Cut API
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/24 (16.67%)   0/22 (0.00%)   1/23 (4.35%) 
Gastrointestinal disorders       
Gastrooesophageal reflux disease * 1  1/24 (4.17%)  0/22 (0.00%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pain in extremity * 1  1/24 (4.17%)  0/22 (0.00%)  0/23 (0.00%) 
Nervous system disorders       
Headache * 1  3/24 (12.50%)  0/22 (0.00%)  0/23 (0.00%) 
Paraesthesia * 1  1/24 (4.17%)  0/22 (0.00%)  0/23 (0.00%) 
Vascular disorders       
Phlebitis * 1  0/24 (0.00%)  0/22 (0.00%)  1/23 (4.35%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 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
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01267201     History of Changes
Other Study ID Numbers: B0121005
First Submitted: December 13, 2010
First Posted: December 28, 2010
Results First Submitted: May 24, 2012
Results First Posted: June 28, 2012
Last Update Posted: June 28, 2012