A Trial To Assess Safety And Tolerability Of PF-04691502 In Cancer Patients
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00927823
Collaborator
(none)
37
7
1
28
5.3
0.2
Study Details
Study Description
Brief Summary
A phase 1 dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of PF-04691502 in adult cancer patients with solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
37 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Dose-Escalation Study To Evaluate Safety, Pharmacokinetics, And Pharmacodynamics Of The PI3K/MTOR Inhibitor PF-04691502 In Adult Patients With Advanced Malignant Solid Tumors
Study Start Date
:
Dec 1, 2009
Actual Primary Completion Date
:
Mar 1, 2011
Actual Study Completion Date
:
Apr 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-04691502 Treatment
|
Drug: PF-04691502
Once daily continuous dosing. Dose escalation to Maximally tolerated dose (MTD) until progression or discontinuation.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to 28 days after the last dose]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
- Number of Participants With Dose Limiting Toxicities (DLTs) [Baseline up to Cycle 1 Day 21]
DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 and defined as any of the following events occurring after first dose of study medication and considered at least possibly-related to study medication. Hematological: grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells per cubic millimeter [cells/mm^3]) for 1 week or greater, febrile neutropenia (fever >=38.5 degree celsius with ANC <1000/mm^3), grade 3 (50,000 cells/mm^3) and grade 4 (<25,000 cells/mm^3) thrombocytopenia; Non-Hematologic: grade 3 or 4 nausea, vomiting, or diarrhea and any clinically significant grade 3 or greater non-hematologic toxicity, despite the use of adequate/maximal medical intervention and/or prophylaxis, and any persistent, intolerable PF-04691502 related toxicity which delayed retreatment for >14 days.
- Recommended Phase-2 Dose (RP2D) [Baseline up to Cycle 1 Day 21]
RP2D was determined based on the safety profile and pharmacodynamic findings, as per investigator's discretion.
Secondary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 21 (C1D21)]
The pharmacokinetics (PK) of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK).
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on C1D21]
The PK of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK).
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only.
- Plasma Decay Half-Life (t1/2) [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours (hrs) post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half-life of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeat oral dose administration for 21 days in Cycle 1 (multiple dose PK).
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period]
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-∞). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only.
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21]
AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where tau is the dosing interval of 24 hours. It was evaluated following repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK) only.
- Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) [Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT]
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8.
- Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) [Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT]
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8.
- Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) [Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT]
Serum glucose level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
- Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) [Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT]
Serum insulin level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
- Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) [Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT]
Serum C-peptide level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
- Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 [Baseline; 4 hours post-dose on C1D21]
Fresh tumor biopsy samples analysis included assessment of status of proteins indicative of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) related pathways signaling status and cell cycle status. The biomarkers included phosphorylated activated kinase (AKT) S473, AKT T308, signal transducer and activator of transcription 3 (STAT3) and forkhead transcription factor Foxo1 (FKHR) T24/forkhead in rhabdomysacoma-like 1 (FKHRL1) T32. The method of analysis was reverse phase microarray (RPMA). The signal (normalized fluorescence unit [NFU]) for each pathway biomarker was normalized against the signal (NFU) for cytokeratin. The final concentration for each pathway biomarker was reported as a cytokeratin normalized fluorescence unit (NFC) value.
- Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 [Baseline; pre-dose, 2, 4, 24 hours post-dose on C1D21]
Hair follicle biopsy samples analysis included assessment of status of proteins indicative of PI3K/mTOR related pathways signaling status and cell cycle status. The analytes measured were phosphorylated AKT S473, AKT T308, KI67, STAT3 (Y705) and proline-rich Akt substrate of 40 kilodaltons at Thr246 (PRAS40 T246). The method of analysis was reverse phase microarray (RPMA). The signal for each biomarker expressed as normalized fluorescence intensity (NFI) was normalized by their respective total protein concentration. This normalization was performed by dividing the biomarker NFI by total protein concentration (mg/mL) of the sample printed to give total protein normalized fluorescence unit (NFU). All clinical sample test results are reported in NFU.
- Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue [Baseline; 4 hours post-dose on C1D21]
Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene mutation, PIK3CA gene amplification, and phosphatase and tensin homolog (PTEN) protein deficiency status by immunohistochemistry.
- Number of Participants With Objective Response [Baseline, prior to Day 1 of Cycle every odd-numbered cycle or when progressive disease was suspected]
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with a histologically or cytologically confirmed malignant solid tumor for which there is no currently approved treatment or which is unresponsive to currently approved therapies.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
-
Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours of the first dose of PF-04961502, These patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate
-
Adequate Bone Marrow Function, including:
-
Absolute neutrophil count (ANC) ≥1500 cells/mm3
-
Platelets ≥75,000 cells/mm3
-
Hemoglobin ≥9 mg/dL
- Adequate Renal Function, including:
SrCr <1.5 x ULN (upper limit of normal). OR Estimated creatinine clearance ≥60 mL/min, as calculated using method standard for the institution
- Adequate Liver Function, including:
Bilirubin ≤1.5 x ULN AST (SGOT) ≤2.5 x ULN ALT (SGPT) ≤2.5 x ULN
-
Adequate glucose control, including no previous diagnosis of diabetes mellitus and HbA1c <7%.
-
Adequate Cardiac Function, including:
12-Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention. QTc interval ≤470 msec and no history of Torsades des Pointes or other symptomatic QTc abnormality
Exclusion Criteria:
-
Patients with known active brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable
-
Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of Baseline disease assessments
-
Any surgery (not including minor procedures such as lymph node biopsy) within 4 weeks of Baseline disease assessments; or not fully recovered from any side effects of previous procedures
-
Prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR
-
Prior high-dose chemotherapy requiring hematopoetic stem cell transplantation within 12 months of study treatment start
-
Uncontrolled or significant cardiovascular disease:
A myocardial infarction within 12 months Uncontrolled angina within 6 months Congestive heart failure within 6 months. Diagnosed or suspected congenital long QT syndrome. Any history of ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). Any history of second or third degree heart block (may be eligible if currently have a pacemaker) Heart rate <50/minute on pre-entry electrocardiogram Uncontrolled hypertension.
-
Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors or inducers
-
Current use or anticipated need for food or drugs that are known potent CYP1A2 inhibitors or inducers
-
Concurrent administration of herbal preparations
-
Breast feeding: No studies have been conducted in humans to assess the impact of PF-04691502 on milk production, its presence in breast milk and its effects on the breast-fed child. Because drugs are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, lactating female patients are excluded from this study.
-
Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form and malabsorption syndrome.
-
Any mental disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Los Angeles | California | United States | 90095-6984 |
| 2 | Pfizer Investigational Site | Los Angeles | California | United States | 90095 |
| 3 | Pfizer Investigational Site | Los Angeles | California | United States | 90404 |
| 4 | Pfizer Investigational Site | Santa Monica | California | United States | 90404 |
| 5 | Pfizer Investigational Site | Detroit | Michigan | United States | 48201 |
| 6 | Pfizer Investigational Site | Amherst | New York | United States | 14221 |
| 7 | Pfizer Investigational Site | Buffalo | New York | United States | 14263 |
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:
NCT00927823
Other Study ID Numbers:
- B1271001
First Posted:
Jun 25, 2009
Last Update Posted:
Aug 12, 2014
Last Verified:
Jul 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 milligram (mg) tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Period Title: Lead-In Period | ||||
| STARTED | 3 | 3 | 26 | 5 |
| COMPLETED | 3 | 3 | 26 | 5 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: Lead-In Period | ||||
| STARTED | 3 | 3 | 26 | 5 |
| Treated | 3 | 3 | 23 | 5 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 3 | 26 | 5 |
Baseline Characteristics
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | All participants received either PF-04691502 2 mg, 4 mg, 8 mg or 11 mg tablet as a single oral dose in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by same PF-04691502 dose orally once daily continuously in 21 day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Overall Participants | 37 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
59.6
(10.5)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
20
54.1%
|
| Male |
17
45.9%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Time Frame | Baseline up to 28 days after the last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all enrolled participants who started the treatment. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| AEs |
3
8.1%
|
3
NaN
|
25
NaN
|
5
NaN
|
| SAEs |
2
5.4%
|
1
NaN
|
15
NaN
|
3
NaN
|
| Title | Number of Participants With Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 and defined as any of the following events occurring after first dose of study medication and considered at least possibly-related to study medication. Hematological: grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells per cubic millimeter [cells/mm^3]) for 1 week or greater, febrile neutropenia (fever >=38.5 degree celsius with ANC <1000/mm^3), grade 3 (50,000 cells/mm^3) and grade 4 (<25,000 cells/mm^3) thrombocytopenia; Non-Hematologic: grade 3 or 4 nausea, vomiting, or diarrhea and any clinically significant grade 3 or greater non-hematologic toxicity, despite the use of adequate/maximal medical intervention and/or prophylaxis, and any persistent, intolerable PF-04691502 related toxicity which delayed retreatment for >14 days. |
| Time Frame | Baseline up to Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all enrolled participants who started the treatment. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Number [participants] |
0
0%
|
0
NaN
|
1
NaN
|
2
NaN
|
| Title | Recommended Phase-2 Dose (RP2D) |
|---|---|
| Description | RP2D was determined based on the safety profile and pharmacodynamic findings, as per investigator's discretion. |
| Time Frame | Baseline up to Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all enrolled participants who started the treatment. |
| Arm/Group Title | PF-04691502 |
|---|---|
| Arm/Group Description | All participants received either PF-04691502 2 mg, 4 mg, 8 mg or 11 mg tablet as a single oral dose in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by same PF-04691502 dose orally once daily continuously in 21 day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 37 |
| Number [milligram] |
8
|
| Title | Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | The pharmacokinetics (PK) of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 21 (C1D21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Single Dose: Cmax (n=3, 3, 26, 5) |
18.07
(13)
|
58.29
(35)
|
66.40
(41)
|
82.51
(15)
|
| Multiple Dose: Cmax (n=3, 3, 20, 1) |
26.30
(19)
|
78.91
(25)
|
102.3
(41)
|
89.8
(NA)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | The PK of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Single Dose: Tmax (n=3, 3, 26, 5) |
4.00
|
0.683
|
2.03
|
4.07
|
| Multiple Dose: Tmax (n=3, 3, 20, 1) |
2.00
|
2.00
|
2.01
|
2.15
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only. |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
330.3
(20)
|
734.4
(18)
|
1130
(41)
|
1320
(32)
|
| 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. Plasma decay half-life of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeat oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours (hrs) post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 milligram (mg) tablet in lead-in period (4 to 10 days prior to Day 1) followed by PF-04691502 2 mg tablet orally, once daily, continuously in 21-day cycles up to 1 year. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Day 1) followed by PF-04691502 4 mg tablet orally, once daily, continuously in 21-day cycles up to 1 year. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Day 1) followed by PF-04691502 8 mg tablet orally, once daily, continuously in 21-day cycles up to 1 year. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Day 1) followed by PF-04691502 11 mg tablet orally, once daily, continuously in 21-day cycles up to 1 year. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Single Dose: t1/2 (n=3, 3, 26, 5) |
13.23
(2.8746)
|
10.87
(0.90738)
|
13.77
(5.2150)
|
11.66
(1.7315)
|
| Multiple Dose: t1/2 (n=1, 0, 5, 1) |
9.19
(NA)
|
NA
(NA)
|
8.984
(0.70840)
|
7.83
(NA)
|
| 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-∞). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only. |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
340.4
(18)
|
741.6
(17)
|
1150
(42)
|
1328
(32)
|
| Title | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) |
|---|---|
| Description | AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where tau is the dosing interval of 24 hours. It was evaluated following repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK) only. |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 20 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
371.7
(5)
|
966.4
(25)
|
1287
(46)
|
1020
|
| Title | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) |
|---|---|
| Description | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8. |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| QTc analysis set included all enrolled participants who had at least 1 ECG assessment after receiving PF-04691502. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Maximum QTcF Interval Increase (Change <30 msec) |
2
5.4%
|
3
NaN
|
19
NaN
|
5
NaN
|
| MaximumQTcF Interval Increase(Change>=30to<60msec) |
1
2.7%
|
0
NaN
|
7
NaN
|
0
NaN
|
| Maximum QTcF Interval Increase (Change >=60 sec) |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) |
|---|---|
| Description | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8. |
| Time Frame | Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| QTc analysis set included all enrolled participants had at least 1 ECG assessment after receiving PF-04691502. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 5 |
| Maximum QTcF Interval (<450 msec) |
2
5.4%
|
3
NaN
|
18
NaN
|
2
NaN
|
| Maximum QTcF Interval (450 to <480 msec) |
1
2.7%
|
0
NaN
|
5
NaN
|
3
NaN
|
| Maximum QTcF Interval (480 to <500 msec) |
0
0%
|
0
NaN
|
3
NaN
|
0
NaN
|
| Maximum QTcF Interval (>=500 msec) |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) |
|---|---|
| Description | Serum glucose level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Time Frame | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serum biomarker analysis set included all enrolled participants who started treatment and had baseline and on-treatment serum biomarker samples (insulin, glucose, and c-peptide) successfully analyzed for at least 1 of the biomarkers. n=participants evaluable at specified time point for each arm, respectively. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 25 | 5 |
| Baseline (n=3, 3, 25, 5) |
87.7
(3.51)
|
84.3
(0.58)
|
87.3
(16.70)
|
91.8
(12.44)
|
| Change at C1D8 (n=3, 3, 23, 5) |
14.0
(7.55)
|
16.7
(27.59)
|
20.0
(25.77)
|
18.8
(5.26)
|
| Change at C1D15 (n=3, 3, 21, 3) |
16.7
(3.79)
|
11.7
(19.66)
|
17.0
(27.23)
|
99.3
(116.43)
|
| Change at C2D1 (n=3, 3, 18, 1) |
8.0
(13.53)
|
4.7
(14.57)
|
36.8
(37.60)
|
0.0
(NA)
|
| Change at C2D15 (n=3, 3, 14, 1) |
12.0
(10.15)
|
11.7
(16.77)
|
22.6
(28.68)
|
32.0
(NA)
|
| Change at C3D1 (n=2, 2, 7, 0) |
39.0
(26.87)
|
15.0
(28.28)
|
36.0
(26.34)
|
NA
(NA)
|
| Change at C4D1 (n=2, 0, 4, 0) |
10.5
(2.12)
|
NA
(NA)
|
35.0
(32.38)
|
NA
(NA)
|
| Change at C5D1 (n=2, 0, 4, 0) |
21.5
(6.36)
|
NA
(NA)
|
71.3
(57.66)
|
NA
(NA)
|
| Change at C6D1 (n=2, 0, 4, 0) |
19.0
(4.24)
|
NA
(NA)
|
7.0
(41.75)
|
NA
(NA)
|
| Change at C7D1 (n=1, 0, 2, 0) |
19.0
(NA)
|
NA
(NA)
|
50.5
(105.36)
|
NA
(NA)
|
| Change at C8D1 (n=1, 0, 1, 0) |
30.0
(NA)
|
NA
(NA)
|
8.0
(NA)
|
NA
(NA)
|
| Change at End of Treatment (n=1, 0, 17, 3) |
33.0
(NA)
|
NA
(NA)
|
43.1
(94.07)
|
13.7
(12.22)
|
| Title | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) |
|---|---|
| Description | Serum insulin level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Time Frame | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable at specified time point for each arm, respectively. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 18 | 4 |
| Baseline (n=3, 3, 18, 4) |
6.2
(2.67)
|
5.8
(3.72)
|
8.0
(5.62)
|
21.4
(25.70)
|
| Change at C1D8 (n=3, 3, 17, 2) |
7.2
(4.17)
|
38.2
(56.39)
|
28.2
(27.34)
|
15.4
(15.13)
|
| Change at C1D15 (n=3, 3, 16, 3) |
5.6
(2.32)
|
8.6
(6.17)
|
25.2
(33.35)
|
60.5
(30.75)
|
| Change at C2D1 (n=2, 3, 13, 0) |
1.4
(1.08)
|
11.4
(8.17)
|
26.1
(17.25)
|
NA
(NA)
|
| Change at C2D15 (n=3, 3, 10, 1) |
-0.1
(8.15)
|
12.0
(6.64)
|
12.3
(10.95)
|
29.2
(NA)
|
| Change at C3D1 (n=2, 2, 4, 0) |
36.0
(45.21)
|
14.8
(16.33)
|
-1.0
(5.92)
|
NA
(NA)
|
| Change at C4D1 (n=1, 0, 4, 0) |
9.1
(NA)
|
NA
(NA)
|
20.3
(15.72)
|
NA
(NA)
|
| Change at C5D1 (n=2, 0, 4, 0) |
5.7
(1.91)
|
NA
(NA)
|
21.2
(14.38)
|
NA
(NA)
|
| Change at C6D1 (n=1, 0, 4, 0) |
1.0
(NA)
|
NA
(NA)
|
13.7
(10.53)
|
NA
(NA)
|
| Change at C7D1 (n=0, 0, 2, 0) |
NA
(NA)
|
NA
(NA)
|
10.4
(14.71)
|
NA
(NA)
|
| Change at C8D1 (n=0, 0, 1, 0) |
NA
(NA)
|
NA
(NA)
|
8.4
(NA)
|
NA
(NA)
|
| Change at End of Treatment (n=1, 0, 10, 2) |
9.0
(NA)
|
NA
(NA)
|
7.8
(14.05)
|
13.1
(3.89)
|
| Title | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) |
|---|---|
| Description | Serum C-peptide level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Time Frame | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable at specified time point for each arm, respectively. Results of PF-04691502 2 mg and 4 mg arm not reported because none of the participants were evaluable. |
| Arm/Group Title | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 13 | 1 |
| Baseline (n=13, 1) |
3.1
(1.79)
|
3.7
|
| Change at C1D8 (n=13, 1) |
5.2
(3.36)
|
2.0
|
| Change at C1D15 (n=12, 0) |
4.4
(3.58)
|
NA
|
| Change at C2D1 (n=10, 0) |
6.2
(3.33)
|
NA
|
| Change at C2D15 (n=8, 0) |
4.5
(3.62)
|
NA
|
| Change at C3D1 (n=3, 0) |
2.0
(1.35)
|
NA
|
| Change at C4D1 (n=1, 0) |
4.9
(NA)
|
NA
|
| Change at C5D1 (n=1, 0) |
4.8
(NA)
|
NA
|
| Change at C6D1 (n=1, 0) |
0.7
(NA)
|
NA
|
| Change at C7D1 (n=1, 0) |
5.8
(NA)
|
NA
|
| Change at C8D1 (n=1, 0) |
1.5
(NA)
|
NA
|
| Change at End of Treatment (n=6, 1) |
3.4
(2.21)
|
0.9
|
| Title | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 |
|---|---|
| Description | Fresh tumor biopsy samples analysis included assessment of status of proteins indicative of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) related pathways signaling status and cell cycle status. The biomarkers included phosphorylated activated kinase (AKT) S473, AKT T308, signal transducer and activator of transcription 3 (STAT3) and forkhead transcription factor Foxo1 (FKHR) T24/forkhead in rhabdomysacoma-like 1 (FKHRL1) T32. The method of analysis was reverse phase microarray (RPMA). The signal (normalized fluorescence unit [NFU]) for each pathway biomarker was normalized against the signal (NFU) for cytokeratin. The final concentration for each pathway biomarker was reported as a cytokeratin normalized fluorescence unit (NFC) value. |
| Time Frame | Baseline; 4 hours post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Fresh tumor biopsy analysis set included all enrolled participants in the tumor biopsy cohort who started treatment and had baseline and on-treatment fresh tumor tissue successfully analyzed for at least 1 of the biomarkers. n=participants evaluable at specified time point. Only PF-04691502 8 mg treatment arm was evaluable for this outcome. |
| Arm/Group Title | PF-04691502 8 mg |
|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 5 |
| Baseline: AKT S473 (n=5) |
98.5
(100.19)
|
| Baseline: AKT T308 (n=4) |
102.9
(61.87)
|
| Baseline: FKHR T24 FKHRL1 T32 (n=5) |
193.4
(120.50)
|
| Baseline: STAT3 (n=5) |
260.9
(192.49)
|
| Change at C1D21: AKT S473 (n=5) |
-72.6
(82.26)
|
| Change at C1D21: AKT T308 (n=4) |
-48.6
(40.37)
|
| Change at C1D21: FKHR T24 FKHRL1 T32 (n=5) |
-81.5
(47.70)
|
| Change at C1D21: STAT3 (n=5) |
-112.2
(78.14)
|
| Title | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 |
|---|---|
| Description | Hair follicle biopsy samples analysis included assessment of status of proteins indicative of PI3K/mTOR related pathways signaling status and cell cycle status. The analytes measured were phosphorylated AKT S473, AKT T308, KI67, STAT3 (Y705) and proline-rich Akt substrate of 40 kilodaltons at Thr246 (PRAS40 T246). The method of analysis was reverse phase microarray (RPMA). The signal for each biomarker expressed as normalized fluorescence intensity (NFI) was normalized by their respective total protein concentration. This normalization was performed by dividing the biomarker NFI by total protein concentration (mg/mL) of the sample printed to give total protein normalized fluorescence unit (NFU). All clinical sample test results are reported in NFU. |
| Time Frame | Baseline; pre-dose, 2, 4, 24 hours post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Hair follicle analysis set included participants with hair follicles collected and analyzed for biomarkers at screening and on treatment. n=participants evaluable at specified time point. Only PF-04691502 8 mg treatment arm was evaluable for this outcome. |
| Arm/Group Title | PF-04691502 8 mg |
|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 10 |
| Baseline: AKT S473 (n=10) |
21.7
(10.47)
|
| Baseline: AKT T308 (n=7) |
50.3
(14.33)
|
| Baseline: KI67 (n=6) |
117.9
(41.19)
|
| Baseline: PRAS40 (T246) (n=7) |
136.7
(37.37)
|
| Baseline: STAT3 (Y705) (n=7) |
189.8
(46.52)
|
| Change at 0 hour: AKT S473 (n=6) |
-3.0
(8.63)
|
| Change at 0 hour: AKT T308 (n=5) |
-5.9
(12.21)
|
| Change at 0 hour: KI67 (n=4) |
2.0
(36.24)
|
| Change at 0 hour: PRAS40 (T246) (n=6) |
-3.7
(39.12)
|
| Change at 0 hour: STAT3 (Y705) (n=4) |
2.5
(39.98)
|
| Change at 2 hours: AKT S473 (n=9) |
-2.5
(5.47)
|
| Change at 2 hours: AKT T308 (n=6) |
-10.9
(13.00)
|
| Change at 2 hours: KI67 (n=5) |
-8.6
(32.67)
|
| Change at 2 hours: PRAS40 (T246) (n=5) |
-21.2
(28.91)
|
| Change at 2 hours: STAT3 (Y705) (n=5) |
21.4
(62.76)
|
| Change at 4 hours: AKT S473 (n=7) |
-2.9
(6.15)
|
| Change at 4 hours: AKT T308 (n=5) |
13.6
(29.98)
|
| Change at 4 hours: KI67 (n=3) |
27.0
(18.39)
|
| Change at 4 hours: PRAS40 (T246) (n=5) |
-15.7
(23.74)
|
| Change at 4 hours: STAT3 (Y705) (n=5) |
-9.3
(48.67)
|
| Change at 24 hours: AKT S473 (n=7) |
3.2
(9.46)
|
| Change at 24 hours: AKT T308 (n=3) |
7.1
(14.89)
|
| Change at 24 hours: KI67 (n=4) |
-12.2
(31.68)
|
| Change at 24 hours: PRAS40 (T246) (n=6) |
10.4
(45.68)
|
| Change at 24 hours: STAT3 (Y705) (n=5) |
-10.8
(65.89)
|
| Title | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue |
|---|---|
| Description | Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene mutation, PIK3CA gene amplification, and phosphatase and tensin homolog (PTEN) protein deficiency status by immunohistochemistry. |
| Time Frame | Baseline; 4 hours post-dose on C1D21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Baseline tumor tissue biomarker analysis set: all enrolled participants who started treatment, had baseline tumor tissues (archived paraffin block/unstained slides/fresh tumor tissue) analyzed for at least 1 of biomarkers. N (number of participants analyzed)=participants evaluable for this measure. n=participants evaluable at specified time point. |
| Arm/Group Title | PF-04691502 |
|---|---|
| Arm/Group Description | All participants received either PF-04691502 2 mg, 4 mg, 8 mg or 11 mg tablet as a single oral dose in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by same PF-04691502 dose orally once daily continuously in 21 day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 18 |
| PTEN status: Present (n=18) |
9
24.3%
|
| PTEN status: Absent (n=18) |
9
24.3%
|
| PIK3CA amplification: Positive (n=17) |
2
5.4%
|
| PIK3CA amplification: Negative (n=17) |
15
40.5%
|
| PIK3CA mutation status: Detectable (n=17) |
3
8.1%
|
| PIK3CA mutation status: Undetectable (n=17) |
14
37.8%
|
| Title | Number of Participants With Objective Response |
|---|---|
| Description | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Time Frame | Baseline, prior to Day 1 of Cycle every odd-numbered cycle or when progressive disease was suspected |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response analysis set included all participants who started treatment and had an adequate baseline tumor assessment. |
| Arm/Group Title | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg |
|---|---|---|---|---|
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. |
| Measure Participants | 3 | 3 | 26 | 4 |
| Number [participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
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 | PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg | ||||
| Arm/Group Description | Single oral dose of PF-04691502 2 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 2 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 8 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 8 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Single oral dose of PF-04691502 11 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 11 mg tablet orally once daily continuously in 21-day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | ||||
All Cause Mortality |
||||||||
| PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 1/3 (33.3%) | 15/26 (57.7%) | 3/5 (60%) | ||||
| Gastrointestinal disorders | ||||||||
| Colitis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Intestinal obstruction | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Small intestinal obstruction | 1/3 (33.3%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Vomiting | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| General disorders | ||||||||
| Disease progression | 0/3 (0%) | 0/3 (0%) | 5/26 (19.2%) | 1/5 (20%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Pneumonia | 0/3 (0%) | 1/3 (33.3%) | 2/26 (7.7%) | 1/5 (20%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercalcaemia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Nervous system disorders | ||||||||
| Transient ischaemic attack | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Dyspnoea | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Pneumonitis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Pulmonary embolism | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Vascular disorders | ||||||||
| Embolism | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| PF-04691502 2 mg | PF-04691502 4 mg | PF-04691502 8 mg | PF-04691502 11 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 24/26 (92.3%) | 5/5 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Leukocytosis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Leukopenia | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Lymphopenia | 0/3 (0%) | 0/3 (0%) | 5/26 (19.2%) | 0/5 (0%) | ||||
| Neutropenia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Thrombocytopenia | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 1/5 (20%) | ||||
| Cardiac disorders | ||||||||
| Nodal rhythm | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Palpitations | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Sinus bradycardia | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Sinus tachycardia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Tachycardia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Ear pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hypoacusis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Tinnitus | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Endocrine disorders | ||||||||
| Hypothyroidism | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Eye disorders | ||||||||
| Conjunctivitis | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Dry eye | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Vision blurred | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Visual acuity reduced | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Visual impairment | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Abdominal hernia | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Abdominal pain | 2/3 (66.7%) | 0/3 (0%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Abdominal pain upper | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Anorectal discomfort | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Chapped lips | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Constipation | 2/3 (66.7%) | 0/3 (0%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Diarrhoea | 2/3 (66.7%) | 1/3 (33.3%) | 8/26 (30.8%) | 1/5 (20%) | ||||
| Dry mouth | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Dyspepsia | 2/3 (66.7%) | 0/3 (0%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Gastritis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Gastrointestinal pain | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Gastrooesophageal reflux disease | 2/3 (66.7%) | 1/3 (33.3%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Glossodynia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Haemorrhoids | 2/3 (66.7%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Irritable bowel syndrome | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Melaena | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Nausea | 3/3 (100%) | 3/3 (100%) | 15/26 (57.7%) | 2/5 (40%) | ||||
| Oral pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Tongue disorder | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Toothache | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Vomiting | 3/3 (100%) | 1/3 (33.3%) | 8/26 (30.8%) | 2/5 (40%) | ||||
| General disorders | ||||||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Chills | 0/3 (0%) | 1/3 (33.3%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Disease progression | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Early satiety | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Fatigue | 1/3 (33.3%) | 1/3 (33.3%) | 17/26 (65.4%) | 4/5 (80%) | ||||
| Feeling hot | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Local swelling | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Mucosal inflammation | 0/3 (0%) | 0/3 (0%) | 5/26 (19.2%) | 2/5 (40%) | ||||
| Oedema | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 1/5 (20%) | ||||
| Oedema peripheral | 0/3 (0%) | 0/3 (0%) | 4/26 (15.4%) | 0/5 (0%) | ||||
| Pain | 1/3 (33.3%) | 0/3 (0%) | 4/26 (15.4%) | 0/5 (0%) | ||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 5/26 (19.2%) | 1/5 (20%) | ||||
| Thirst | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Immune system disorders | ||||||||
| Seasonal allergy | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Candidiasis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Chronic sinusitis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Infection | 0/3 (0%) | 1/3 (33.3%) | 0/26 (0%) | 1/5 (20%) | ||||
| Liver abscess | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Oral candidiasis | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Oral herpes | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 3/26 (11.5%) | 2/5 (40%) | ||||
| Viral infection | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Fall | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Mouth injury | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Post procedural fistula | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Post procedural haemorrhage | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Procedural pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Blood creatinine increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Breath sounds abnormal | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Electrocardiogram QT prolonged | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Eosinophil count increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Glycosylated haemoglobin increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| International normalised ratio increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Platelet count decreased | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Troponin increased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Urine output decreased | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Weight decreased | 1/3 (33.3%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/3 (33.3%) | 2/3 (66.7%) | 11/26 (42.3%) | 3/5 (60%) | ||||
| Dehydration | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 1/5 (20%) | ||||
| Hypercholesterolaemia | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Hyperglycaemia | 2/3 (66.7%) | 0/3 (0%) | 10/26 (38.5%) | 1/5 (20%) | ||||
| Hypoalbuminaemia | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hypokalaemia | 1/3 (33.3%) | 0/3 (0%) | 6/26 (23.1%) | 0/5 (0%) | ||||
| Hyponatraemia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 2/5 (40%) | ||||
| Hypophosphataemia | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Iron deficiency | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Lactic acidosis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Polydipsia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/3 (0%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Arthritis | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Arthropathy | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Back pain | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Bone pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Flank pain | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Intervertebral disc degeneration | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Muscle spasms | 0/3 (0%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Musculoskeletal chest pain | 0/3 (0%) | 1/3 (33.3%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Musculoskeletal discomfort | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Myalgia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Neck pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Osteoarthritis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Osteoporosis | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Cancer pain | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Malignant pleural effusion | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Nervous system disorders | ||||||||
| Balance disorder | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Convulsion | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Dizziness | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Dysgeusia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Headache | 1/3 (33.3%) | 1/3 (33.3%) | 4/26 (15.4%) | 2/5 (40%) | ||||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Neuropathy peripheral | 2/3 (66.7%) | 0/3 (0%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Paraesthesia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Sinus headache | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Trigeminal neuralgia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Anxiety | 1/3 (33.3%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Depression | 1/3 (33.3%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Insomnia | 1/3 (33.3%) | 0/3 (0%) | 5/26 (19.2%) | 0/5 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Nocturia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Polyuria | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Proteinuria | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Renal failure acute | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Sexual dysfunction | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 1/3 (33.3%) | 0/3 (0%) | 0/26 (0%) | 0/5 (0%) | ||||
| Cough | 0/3 (0%) | 0/3 (0%) | 3/26 (11.5%) | 1/5 (20%) | ||||
| Dysphonia | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Dyspnoea | 0/3 (0%) | 0/3 (0%) | 4/26 (15.4%) | 2/5 (40%) | ||||
| Dyspnoea exertional | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Epistaxis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 1/5 (20%) | ||||
| Haemoptysis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hypoxia | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Pulmonary congestion | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Cold sweat | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Dermatitis acneiform | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Dry skin | 0/3 (0%) | 0/3 (0%) | 4/26 (15.4%) | 0/5 (0%) | ||||
| Generalised erythema | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hair texture abnormal | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Pruritus | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Rash | 0/3 (0%) | 0/3 (0%) | 7/26 (26.9%) | 2/5 (40%) | ||||
| Rash generalised | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Rash macular | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Rash papular | 0/3 (0%) | 0/3 (0%) | 0/26 (0%) | 1/5 (20%) | ||||
| Skin discolouration | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Skin lesion | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Swelling face | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
| Flushing | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 0/5 (0%) | ||||
| Hypertension | 1/3 (33.3%) | 0/3 (0%) | 3/26 (11.5%) | 0/5 (0%) | ||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 2/26 (7.7%) | 1/5 (20%) | ||||
| Thrombosis | 0/3 (0%) | 0/3 (0%) | 1/26 (3.8%) | 0/5 (0%) | ||||
Limitations/Caveats
[Not Specified]
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 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 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00927823
Other Study ID Numbers:
- B1271001
First Posted:
Jun 25, 2009
Last Update Posted:
Aug 12, 2014
Last Verified:
Jul 1, 2014