Bioequivalence And Food Effect Study Comparing The Commercial Formulation Of Crizotinib To Its Clinical Study Formulations And Commercial Formulation With Or Without Food In Healthy Volunteers
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01154218
Collaborator
(none)
36
1
1
3
11.9
Study Details
Study Description
Brief Summary
The purpose of this study is to demonstrate bioequivalence of the Commercial Image Capsule (CIC) relative to the Immediate Release Tablet (IRT) of crizotinib, bioequivalence of CIC relative to Powder in Capsule (PIC) of crizotinib, and lack of an effect of high fat meal on the pharmacokinetics (PK) of crizotinib when administered as CIC Formulation in healthy volunteers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The purpose of this study is to demonstrate bioequivalence of the CIC relative to IRT and CIC relative to PIC, and lack of an effect of food on the PK of crizotinib in healthy volunteers.
Study Design
Study Type:
Interventional
Actual Enrollment
:
36 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Official Title:
A Phase 1, Single Dose Bioequivalence And Food Effect Study In Healthy Volunteers Comparing The Commercial Image Capsules To The Immediate Release Tablets And Powder In Capsule Formulations Of Crizotinib (PF-02341066), And The Commercial Image Capsule In The Fasted To Fed State
Study Start Date
:
Aug 1, 2010
Actual Primary Completion Date
:
Nov 1, 2010
Actual Study Completion Date
:
Nov 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 All subjects will receive four treatments in one of the indicated orders: A-B-C-D, B-D-A-C, C-A-D-B, D-C-B-A |
Drug: crizotinib
Treatment A (Reference 1): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg IRT and 2 × 100-mg IRTs.
Treatment B (Reference 2): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg PIC and 2 × 100 mg PICs.
Treatment C (Test for BE, Reference for Food Effect): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 250-mg CIC.
Treatment D (Test High Fat): a 250 mg single dose of crizotinib administered with a high-fat meal as 1 × 250-mg CIC
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose]
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-∞).
- Maximum Observed Plasma Concentration (Cmax) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Secondary Outcome Measures
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
- Plasma Decay Half Life (t1/2) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Apparent Oral Clearance (CL/F) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
- Apparent Volume of Distribution (Vz/F) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182).
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
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-∞).
- Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Healthy male and/or female of non-childbearing potential subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
-
Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight >50 kg (110 lbs)
Exclusion Criteria:
- Subjects who are smoking, or with evidence of disease, conditions affecting absorption, treatment with other investigational drug within 30 days, history of regular alcohol consumption, use of prescription, nonprescription drugs and dietary supplement within 7 days, or blood donation of 500 mL within 56 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Bruxelles | Belgium | B-1070 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01154218
Other Study ID Numbers:
- A8081011
First Posted:
Jun 30, 2010
Last Update Posted:
Oct 24, 2011
Last Verified:
Oct 1, 2011
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed | Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted | Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted | Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 milligram (mg) immediate release tablet (IRT) in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg powder in capsule (PIC) in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg commercial image capsule (CIC) in fasted state in third intervention period; and single oral dose of crizotinib 250 mg CIC in fed state in fourth intervention period. A washout period of at least 14 days was maintained between each period. | Single oral dose of crizotinib 250 mg PIC in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg CIC in fed state in second intervention period; followed by single oral dose of crizotinib 250 mg IRT in fasted state in third intervention period; and single oral dose of crizotinib 250 mg CIC in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period. | Single oral dose of crizotinib 250 mg CIC in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg IRT in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg CIC in fed state in third intervention period; and single oral dose of crizotinib 250 mg PIC in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period. | Single oral dose of crizotinib 250 mg CIC in fed state in first intervention period; followed by single oral dose of crizotinib 250 mg CIC in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg PIC in fasted state in third intervention period; and single oral dose of crizotinib 250 mg IRT in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period. |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 9 | 9 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 9 | 9 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 9 | 9 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 9 | 9 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 8 | 9 | 9 |
| NOT COMPLETED | 0 | 1 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 8 | 9 | 9 |
| COMPLETED | 9 | 8 | 9 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 1 |
| Period Title: First Intervention Period | ||||
| STARTED | 9 | 8 | 9 | 8 |
| COMPLETED | 8 | 8 | 9 | 8 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | Includes participants randomized to receive any treatment (crizotinib 250 mg IRT fasted first, crizotinib 250 mg PIC fasted first, crizotinib 250 mg CIC fasted first and crizotinib 250 mg CIC fed). |
| Overall Participants | 36 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
38.9
(8.1)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
36
100%
|
Outcome Measures
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) |
|---|---|
| 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), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
2890.0
(1021.8)
|
2665.0
(1190.4)
|
2887.0
(1109.6)
|
2475.0
(1037.7)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted Means |
| Estimated Value | 99.56 | |
| Confidence Interval |
(2-Sided) 90% 91.49 to 108.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 106.93 | |
| Confidence Interval |
(2-Sided) 90% 98.26 to 116.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted Means |
| Estimated Value | 85.76 | |
| Confidence Interval |
(2-Sided) 90% 78.88 to 93.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
|---|---|
| Description | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast). |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
2763.0
(989.0)
|
2531.0
(1158.0)
|
2761.0
(1078.4)
|
2359.0
(1013.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUClast of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 99.60 | |
| Confidence Interval |
(2-Sided) 90% 91.30 to 108.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUClast of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 107.56 | |
| Confidence Interval |
(2-Sided) 90% 98.58 to 117.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed AUClast of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 85.52 | |
| Confidence Interval |
(2-Sided) 90% 78.45 to 93.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Median (Full Range) [hr] |
5.00
|
5.00
|
5.00
|
5.00
|
| Title | Plasma Decay Half Life (t1/2) |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Mean (Standard Deviation) [hr] |
34.62
(4.13)
|
35.28
(6.39)
|
34.85
(4.94)
|
35.41
(5.49)
|
| Title | Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [ng/mL] |
126.00
(36.58)
|
119.30
(50.88)
|
135.00
(47.84)
|
116.10
(45.58)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed Cmax of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted Means |
| Estimated Value | 106.97 | |
| Confidence Interval |
(2-Sided) 90% 96.55 to 118.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed Cmax of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted Means |
| Estimated Value | 111.32 | |
| Confidence Interval |
(2-Sided) 90% 100.47 to 123.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed Cmax of crizotinib was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted Means |
| Estimated Value | 86.22 | |
| Confidence Interval |
(2-Sided) 90% 77.89 to 95.43 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Apparent Oral Clearance (CL/F) |
|---|---|
| Description | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [L/hr] |
86.49
(30.42)
|
93.78
(49.80)
|
86.57
(53.63)
|
101.00
(38.60)
|
| Title | Apparent Volume of Distribution (Vz/F) |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [L] |
4290.0
(1672.4)
|
4703.0
(2874.7)
|
4313.0
(3880.9)
|
5096.0
(2302.0)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) |
|---|---|
| Description | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182). |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
432.20
(219.76)
|
391.20
(255.12)
|
436.90
(246.34)
|
325.00
(192.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUClast of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 100.03 | |
| Confidence Interval |
(2-Sided) 90% 90.16 to 110.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUClast of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 108.85 | |
| Confidence Interval |
(2-Sided) 90% 98.11 to 120.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed AUClast of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 74.87 | |
| Confidence Interval |
(2-Sided) 90% 67.55 to 82.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) |
|---|---|
| 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), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the 'N = 35' is signifying those participants who were evaluable for this measure at the specified time point for crizotinib CIC fed arm group. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 35 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
442.00
(221.96)
|
402.10
(257.39)
|
447.10
(248.23)
|
341.80
(194.91)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 100.08 | |
| Confidence Interval |
(2-Sided) 90% 90.46 to 110.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 108.47 | |
| Confidence Interval |
(2-Sided) 90% 98.03 to 120.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 76.59 | |
| Confidence Interval |
(2-Sided) 90% 69.23 to 84.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Geometric Mean (Standard Deviation) [ng/mL] |
32.20
(12.48)
|
29.74
(15.19)
|
33.04
(12.12)
|
23.64
(10.85)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib IRT Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed Cmax of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 102.11 | |
| Confidence Interval |
(2-Sided) 90% 92.84 to 112.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib PIC Fasted, Crizotinib CIC Fasted |
|---|---|---|
| Comments | Natural log transformed Cmax of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 108.87 | |
| Confidence Interval |
(2-Sided) 90% 98.98 to 119.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Crizotinib CIC Fasted, Crizotinib CIC Fed |
|---|---|---|
| Comments | Natural log transformed Cmax of PF-06260182 was analyzed using a 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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Adjusted means |
| Estimated Value | 71.94 | |
| Confidence Interval |
(2-Sided) 90% 65.46 to 79.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. |
| Arm/Group Title | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. |
| Measure Participants | 35 | 35 | 35 | 36 |
| Median (Full Range) [hr] |
6.00
|
6.00
|
5.00
|
6.00
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| 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 | Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed | ||||
| Arm/Group Description | Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period. | Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period. | ||||
All Cause Mortality |
||||||||
| Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Crizotinib IRT Fasted | Crizotinib PIC Fasted | Crizotinib CIC Fasted | Crizotinib CIC Fed | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/36 (58.3%) | 24/36 (66.7%) | 20/36 (55.6%) | 21/36 (58.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | 0/36 (0%) | ||||
| Abdominal distension | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Abdominal pain | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 2/36 (5.6%) | ||||
| Abdominal pain upper | 2/36 (5.6%) | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | ||||
| Constipation | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Diarrhoea | 9/36 (25%) | 13/36 (36.1%) | 13/36 (36.1%) | 13/36 (36.1%) | ||||
| Dyspepsia | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 1/36 (2.8%) | ||||
| Epigastric discomfort | 2/36 (5.6%) | 1/36 (2.8%) | 2/36 (5.6%) | 0/36 (0%) | ||||
| Flatulence | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 1/36 (2.8%) | ||||
| Gastrointestinal sounds abnormal | 1/36 (2.8%) | 0/36 (0%) | 1/36 (2.8%) | 2/36 (5.6%) | ||||
| Gingivitis | 0/36 (0%) | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | ||||
| Nausea | 5/36 (13.9%) | 10/36 (27.8%) | 2/36 (5.6%) | 5/36 (13.9%) | ||||
| Salivary hypersecretion | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | 0/36 (0%) | ||||
| Vomiting | 0/36 (0%) | 2/36 (5.6%) | 0/36 (0%) | 0/36 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 3/36 (8.3%) | 5/36 (13.9%) | 2/36 (5.6%) | 1/36 (2.8%) | ||||
| Feeling cold | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 2/36 (5.6%) | 3/36 (8.3%) | 0/36 (0%) | 1/36 (2.8%) | ||||
| Tooth abscess | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 1/36 (2.8%) | ||||
| Urinary tract infection | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 1/36 (2.8%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Joint sprain | 1/36 (2.8%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Investigations | ||||||||
| Hepatic enzyme increased | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Neck pain | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Dizziness postural | 0/36 (0%) | 1/36 (2.8%) | 0/36 (0%) | 0/36 (0%) | ||||
| Headache | 4/36 (11.1%) | 5/36 (13.9%) | 4/36 (11.1%) | 3/36 (8.3%) | ||||
| Paraesthesia | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | ||||
| Somnolence | 1/36 (2.8%) | 1/36 (2.8%) | 1/36 (2.8%) | 3/36 (8.3%) | ||||
| Vascular disorders | ||||||||
| Hot flush | 0/36 (0%) | 0/36 (0%) | 0/36 (0%) | 1/36 (2.8%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01154218
Other Study ID Numbers:
- A8081011
First Posted:
Jun 30, 2010
Last Update Posted:
Oct 24, 2011
Last Verified:
Oct 1, 2011