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PD-0332991 may work in cancer by stopping cancer cells from multiplying. PD-0332991 is in a new class of drugs called cyclin-dependent kinase (CDK inhibitors). This research study is the first time that PD-0332991 will be given to people. PD-0332991 is taken by mouth daily.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PD-0332991 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-0332991 | Drug | Dose ranging study - evaluating two oral schedule: (1) 3/1 Schedule - PD-0332991 administered days 1-21 of a 28-day schedule, doses ranging from 25 to 150 mg once daily; (2) 2/1 Schedule - PD-0332991 administered days 1-14 of a 21-days schedule, doses ranging from 100 to 225 mg once daily |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLT) | DLT: an adverse event occurring after initiation of PD 0332991 that met any following criteria: 1) Grade 4 hematologic toxicity (platelets less than [<] 25000 per microliter (mcL), absolute neutrophil count [ANC] <500/mcL, hemoglobin [Hb] <6.5 gram per deciliter [g/dL]; 2) ANC <1000/mcL associated with documented infection or fever greater than or equal to (>=) 38.5 degrees Celsius; 3) >=Grade 3 non-hematologic treatment-related toxicity. In an asymptomatic participant, Grade 3 corrected QT (QTc) prolongation (>500 millisecond) (only if persisted with repeat testing and after correction of reversible causes [electrolyte abnormalities or hypoxia]); and 4) Inability to receive next dose of PD 0332991 within 1 week (+/-1 day) of last dose due to lack of hematologic recovery (platelets <50000/mcL, ANC <1000/mcL, and Hb <8.0 g/dL) or due to prolonged non-hematologic toxicities of >=Grade 3 severity. Occurrence of a DLT necessitated immediate interruption of scheduled study treatment. | Baseline up to 28 days |
| Maximum Administered Dose (MAD) | Three new evaluable participants were to be assessed at each new dose level. The minimum time that these participants were to be followed after starting treatment was 1 cycle (28 or 21 days) before a new dose level could be opened. If none of these 3 participants experienced a DLT, the next higher dose level was to be opened on that schedule. If 1 participant developed a DLT, 3 more evaluable participants were to be enrolled at that dose level; if none of these additional 3 participants developed a DLT, the next higher dose level was to be opened on that schedule. If >=2 participants experienced a first cycle DLT at the same dose level and schedule, that dose level was to be defined as the MAD for that schedule. No additional participants were to be entered at the MAD for that dosing schedule. DLT is defined in Outcome Measure 1. | Baseline up to 28 days |
| Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D) | MTD was defined as the highest dose level studied for which the incidence of first cycle DLT was <33%. Once MTD was determined, it was defined as RP2D. DLT is defined in Outcome Measure 1. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States | ||
| Memorial Sloan Kettering Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19238148 | Derived | Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602. | |
| 19164198 | Derived | Vaughn DJ, Flaherty K, Lal P, Gallagher M, O'Dwyer P, Wilner K, Chen I, Schwartz G. Treatment of growing teratoma syndrome. N Engl J Med. 2009 Jan 22;360(4):423-4. doi: 10.1056/NEJMc0808558. No abstract available. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | PD 0332991 25 mg QD (21/28 Days) | PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG001 | PD 0332991 50 mg QD (21/28 Days) | PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG002 | PD 0332991 75 mg QD (21/28 Days) | PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG003 | PD 0332991 100 mg QD (21/28 Days) | PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG004 | PD 0332991 125 mg QD (21/28 Days) | PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG005 | PD 0332991 150 mg QD (21/28 Days) | PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG006 | PD 0332991 100 mg QD (14/21 Days) | PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG007 | PD 0332991 150 mg QD (14/21 Days) | PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG008 | PD 0332991 200 mg QD (14/21 Days) | PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| FG009 | PD 0332991 225 mg QD (14/21 Days) | PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Full Analysis Set (FAS) included all enrolled participants who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | PD 0332991 (21/28 Days) | Participants received PD 0332991 capsule orally once daily (QD), continuously for 21 days in 28-day cycles in dose escalation schemes of 25 mg, 50 mg, 75 mg, 100 mg, 125 mg and 150 mg. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicities (DLT) | DLT: an adverse event occurring after initiation of PD 0332991 that met any following criteria: 1) Grade 4 hematologic toxicity (platelets less than [<] 25000 per microliter (mcL), absolute neutrophil count [ANC] <500/mcL, hemoglobin [Hb] <6.5 gram per deciliter [g/dL]; 2) ANC <1000/mcL associated with documented infection or fever greater than or equal to (>=) 38.5 degrees Celsius; 3) >=Grade 3 non-hematologic treatment-related toxicity. In an asymptomatic participant, Grade 3 corrected QT (QTc) prolongation (>500 millisecond) (only if persisted with repeat testing and after correction of reversible causes [electrolyte abnormalities or hypoxia]); and 4) Inability to receive next dose of PD 0332991 within 1 week (+/-1 day) of last dose due to lack of hematologic recovery (platelets <50000/mcL, ANC <1000/mcL, and Hb <8.0 g/dL) or due to prolonged non-hematologic toxicities of >=Grade 3 severity. Occurrence of a DLT necessitated immediate interruption of scheduled study treatment. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | participants | Baseline up to 28 days |
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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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PD 0332991 25 mg QD (21/28 Days) | PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 11.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C500026 | palbociclib |
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| Baseline up to 28 days |
| Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | DLT is defined in Outcome Measure 1. Hematologic (Grade 4 [life-threatening or disabling]) and non-hematologic (Grade 3 [severe], 4 [life-threatening and disabling], 5 [resulting in death]) DLTs are reported separately. A single participant may experience more than one DLT. Both treatment-related and treatment-unrelated DLT events were reported for this outcome measure. | Baseline up to 28 days |
| Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. For clinical description of nature (severity) of AEs, AEs were grades as: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening or disabling AE; and Grade 5: death related to AE. AEs during Cycle 1 and AEs post Cycle 1 are reported separately. | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) |
| Number of Participants With Treatment-Related Treatment Emergent Adverse Events | A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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. AEs during Cycle 1 and AEs post Cycle 1 are reported separately. | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) |
| Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment. 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. Relatedness [to study drug] was assessed by the investigator (Yes/No). | Baseline up to 30 days after end of treatment (up to Cycle 93) |
| Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | The mean Cmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect | To determine the impact of food (specifically a high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In this crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. The first 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, the next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. The high-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of the total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | The median Tmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect | To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Terminal Half-life (t½ ) on Day 1: Single Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Terminal Half-life (t½ ) on Day 8: Multiple Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. The mean t1/2 for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Terminal Half-life (t½ ) on Day 1: Food Effect | To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). The mean AUClast for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Area Under the Curve From Time Zero to End of the Dosing Interval [AUC(0 to Tau)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Area under the curve from time zero to end of the dosing interval (24 hours) [AUC (0-tau)]. The mean AUC (0-tau) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single 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 - ∞). | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple 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 - ∞). | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Apparent Oral Clearance (CL/F) on Day 1: Single Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. The mean CL/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Apparent Oral Clearance (CL/F) on Day 1: Food Effect | Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Apparent Volume of Distribution (Vz/F) on Day 1: Single 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Apparent Volume of Distribution (Vz/F) on Day 8: Multiple 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. The mean Vz/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect | Volume of distribution: theoretical volume in which total amount of drug would need to be uniformly distributed to produce desired plasma concentration. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Accumulation Ratio (Rac) on Day 8: Multiple Dose | Rac at Day 8 = AUC (0-tau) at Day 8 divided by AUC (0-tau) at Day 1. | Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8 |
| Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Rac at Day 14/21 = AUC (0-tau) at Day 14/21 divided by AUC (0-tau) at Day 1. The mean Rac for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
| Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
| Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. The mean lambda (z) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
| Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect | Terminal phase rate constant: absolute value of slope of a linear regression during terminal phase of natural-logarithm transformed concentration-time profile. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
| Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose | Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Urine PK analysis was performed only in the MTD/RP2D groups (125 mg [21/28 Days] and 200 mg [14/21 Days]). | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
| Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect | The Ae is defined in Outcome Measure 42. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
| Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose | Percent of dose recovered unchanged in urine over the 10 hour collection interval=100*(Ae divided by dose). Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
| Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect | The percent Ae is defined in Outcome Measure 44. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
| Number of Participants With Best Response | Number of participants with best response. Complete response (CR): disappearance of all target and non-target lesions. Partial Response (PR): >=30% decrease in sum of longest diameter (LD) of lesions taking as reference baseline sum LD and no unequivocal progression in non-target lesions. Progressive disease (PD): >=20% increase in sum of LD of lesions taking as a reference smallest sum of the LD since treatment start, or the appearance of >=1 new lesion or unequivocal progression of existing non-target lesions. Stable disease (SD): neither shrinkage for PR nor increase for PD taking as reference smallest sum of LD since treatment start. SD was assessed following the first 2 cycles of treatment (>=2 cycles), 4 cycles of treatment (>=4 cycles), and 10 cycles of treatment (>=10 cycles). Participants may be reported in more than 1 category of SD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. | Baseline up to end of treatment, assessed at C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
| Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue and p-Rb levels (fold decrease) were to be reported. | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with respect to PD 0322991 dose. | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with PD 0322991 exposure. | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with tumor response. | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
| New York |
| New York |
| 10065 |
| United States |
| Abramson Cancer Center Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Pharmacy/PCAM/West Pavillion | Philadelphia | Pennsylvania | 19104 | United States |
| Death |
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| Withdrawal by Subject |
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| Other |
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| Progressive Disease |
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| Transitioned |
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| BG001 |
| PD 0332991 (14/21 Days) |
Participants received PD 0332991 capsule orally once daily (QD), continuously for 14 days in 21-day cycles in dose escalation schemes of 100 mg, 150 mg and 200 mg, 225 mg. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| ID | Title | Description |
|---|
| OG000 | PD 0332991 25 mg QD (21/28 Days) | PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG001 | PD 0332991 50 mg QD (21/28 Days) | PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG002 | PD 0332991 75 mg QD (21/28 Days) | PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG003 | PD 0332991 100 mg QD (21/28 Days) | PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG004 | PD 0332991 125 mg QD (21/28 Days) | PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG005 | PD 0332991 150 mg QD (21/28 Days) | PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG006 | PD 0332991 100 mg QD (14/21 Days) | PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG007 | PD 0332991 150 mg QD (14/21 Days) | PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG008 | PD 0332991 200 mg QD (14/21 Days) | PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
| OG009 | PD 0332991 225 mg QD (14/21 Days) | PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. |
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| Primary | Maximum Administered Dose (MAD) | Three new evaluable participants were to be assessed at each new dose level. The minimum time that these participants were to be followed after starting treatment was 1 cycle (28 or 21 days) before a new dose level could be opened. If none of these 3 participants experienced a DLT, the next higher dose level was to be opened on that schedule. If 1 participant developed a DLT, 3 more evaluable participants were to be enrolled at that dose level; if none of these additional 3 participants developed a DLT, the next higher dose level was to be opened on that schedule. If >=2 participants experienced a first cycle DLT at the same dose level and schedule, that dose level was to be defined as the MAD for that schedule. No additional participants were to be entered at the MAD for that dosing schedule. DLT is defined in Outcome Measure 1. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | milligram | Baseline up to 28 days |
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| Primary | Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D) | MTD was defined as the highest dose level studied for which the incidence of first cycle DLT was <33%. Once MTD was determined, it was defined as RP2D. DLT is defined in Outcome Measure 1. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | milligram | Baseline up to 28 days |
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| Primary | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | DLT is defined in Outcome Measure 1. Hematologic (Grade 4 [life-threatening or disabling]) and non-hematologic (Grade 3 [severe], 4 [life-threatening and disabling], 5 [resulting in death]) DLTs are reported separately. A single participant may experience more than one DLT. Both treatment-related and treatment-unrelated DLT events were reported for this outcome measure. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | DLTs | Baseline up to 28 days |
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| Primary | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. For clinical description of nature (severity) of AEs, AEs were grades as: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening or disabling AE; and Grade 5: death related to AE. AEs during Cycle 1 and AEs post Cycle 1 are reported separately. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | participants | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) |
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| Primary | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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. AEs during Cycle 1 and AEs post Cycle 1 are reported separately. | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | participants | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) |
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| Primary | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment. 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. Relatedness [to study drug] was assessed by the investigator (Yes/No). | FAS included all enrolled participants who received at least one dose of study medication. | Posted | Number | participants | Baseline up to 30 days after end of treatment (up to Cycle 93) |
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| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | Pharmacokinetic (PK) analysis set included all participants from FAS who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | The mean Cmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect | To determine the impact of food (specifically a high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In this crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. The first 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, the next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. The high-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of the total caloric content. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. | Posted | Median | Full Range | hours | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | The median Tmax for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect | To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Median | Full Range | hours | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Terminal Half-life (t½ ) on Day 1: Single Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | It was not possible to calculate data for t½ as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase, which is needed for the calculation of the t½. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Terminal Half-life (t½ ) on Day 8: Multiple Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | It was not possible to calculate data for t½ as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase, which is needed for the calculation of the t½. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Terminal half-life is the time measured for the plasma concentration to decrease by one half. The mean t1/2 for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | hours | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Terminal Half-life (t½ ) on Day 1: Food Effect | To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | It was not possible to calculate data for t½ as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase, which is needed for the calculation of the t½. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | nanogram*hour/milliliter (ng*hour/mL) | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng*hour/mL | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). The mean AUClast for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng*hour/mL | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results are reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng*hour/mL | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Area Under the Curve From Time Zero to End of the Dosing Interval [AUC(0 to Tau)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Area under the curve from time zero to end of the dosing interval (24 hours) [AUC (0-tau)]. The mean AUC (0-tau) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng*hour/mL | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single 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 - ∞). | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the AUC (0 - ∞). | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple 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 - ∞). | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the AUC (0 - ∞). | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the AUC (0 - ∞). | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Apparent Oral Clearance (CL/F) on Day 1: Single Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the CL/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the CL/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. The mean CL/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | liter/hour | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Apparent Oral Clearance (CL/F) on Day 1: Food Effect | Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the CL/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Apparent Volume of Distribution (Vz/F) on Day 1: Single 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the Vz/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Apparent Volume of Distribution (Vz/F) on Day 8: Multiple 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the Vz/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. The mean Vz/F for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | liter | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect | Volume of distribution: theoretical volume in which total amount of drug would need to be uniformly distributed to produce desired plasma concentration. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the Vz/F. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Accumulation Ratio (Rac) on Day 8: Multiple Dose | Rac at Day 8 = AUC (0-tau) at Day 8 divided by AUC (0-tau) at Day 1. | It was not possible to calculate data for this outcome measure because calculation was dependent on the linear regression of data points collected during the terminal phase and the PK sampling was insufficient to characterize the terminal phase, which is needed for the calculation of the Rac. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8 |
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| Primary | Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Rac at Day 14/21 = AUC (0-tau) at Day 14/21 divided by AUC (0-tau) at Day 1. The mean Rac for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ratio | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile. | It was not possible to calculate data as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1) |
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| Primary | Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. | It was not possible to calculate the data as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8) |
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| Primary | Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm transformed concentration-time profile. The mean lambda (z) for 200 mg dose group (dose corrected to 125 mg) on Cycle 1 Day 14 (C1D14) and 125 mg dose group on Cycle 1 Day 21 (C1D21) was calculated. Only participants from 125 mg and 200 mg dose groups were reported. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | 1/hour | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days) |
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| Primary | Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect | Terminal phase rate constant: absolute value of slope of a linear regression during terminal phase of natural-logarithm transformed concentration-time profile. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | It was not possible to calculate the data as the calculation required the slope of terminal elimination phase and the PK sampling was insufficient to characterize the terminal elimination phase. | Posted | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 |
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| Primary | Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose | Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Urine PK analysis was performed only in the MTD/RP2D groups (125 mg [21/28 Days] and 200 mg [14/21 Days]). | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | microgram (mcg) | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
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| Primary | Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect | The Ae is defined in Outcome Measure 42. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol. | Posted | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
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| Primary | Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose | Percent of dose recovered unchanged in urine over the 10 hour collection interval=100*(Ae divided by dose). Ae is the cumulative amount of drug recovered unchanged in urine over the 10 hour collection interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. | PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day. Here "N" (number of participants analyzed) signifies participant who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | percentage of dose | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
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| Primary | Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect | The percent Ae is defined in Outcome Measure 44. To determine impact of food (specifically high-fat meal) on PD 0332991 PK, participants were tested under fed and fasted conditions in crossover fashion. Each participant served as their own control. In crossover fashion first dose was administered under either fed (high-fat meal) or fasted (10-hour fast) condition on Day 1 of Cycle 1 and 2. First 6 participants were tested under fed (on C1D1) followed by fasted (on C2D1) conditions, next 6 participants were tested under fasted (on C1D1) followed by fed (on C2D1) conditions. Only participants in PD 0332991 200 mg (14/21 days) and 125 mg (21/28 days) groups participated in food effect crossover and results were to be reported as per fed and fasted conditions. High-fat meal was composed of around 800 to 1000 calories total, with fat composing around 50% of total caloric content. | Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol. | Posted | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 |
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| Primary | Number of Participants With Best Response | Number of participants with best response. Complete response (CR): disappearance of all target and non-target lesions. Partial Response (PR): >=30% decrease in sum of longest diameter (LD) of lesions taking as reference baseline sum LD and no unequivocal progression in non-target lesions. Progressive disease (PD): >=20% increase in sum of LD of lesions taking as a reference smallest sum of the LD since treatment start, or the appearance of >=1 new lesion or unequivocal progression of existing non-target lesions. Stable disease (SD): neither shrinkage for PR nor increase for PD taking as reference smallest sum of LD since treatment start. SD was assessed following the first 2 cycles of treatment (>=2 cycles), 4 cycles of treatment (>=4 cycles), and 10 cycles of treatment (>=10 cycles). Participants may be reported in more than 1 category of SD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. | Modified Full Analysis Set included all enrolled participants who received at least 1 dose of study medication in Cycle 1 and completed a post-treatment response assessment. | Posted | Number | participants | Baseline up to end of treatment, assessed at C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
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| Primary | Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue and p-Rb levels (fold decrease) were to be reported. | Data was reported in individual participant listings and not summarized due to change in planned analysis, where baseline and post-baseline tumor biopsies for biomarkers were no longer required and were not obtained for all participants. | Posted | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
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| Primary | Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with respect to PD 0322991 dose. | Data was reported in individual participant listings and not summarized due to change in planned analysis, where baseline and post-baseline tumor biopsies for biomarkers were no longer required and were not obtained for all participants. | Posted | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
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| Primary | Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with PD 0322991 exposure. | Data was reported in individual participant listings and not summarized due to change in planned analysis, where baseline and post-baseline tumor biopsies for biomarkers were no longer required and were not obtained for all participants. | Posted | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
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| Primary | Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response | Phosphorylation of the retinoblastoma (Rb) protein by Cdk4/6 is typically required for human cancer cell proliferation. Tumor biopsies were to be performed, to demonstrate inhibition of Cdk4/6 based on reduction in phosphorylated Rb (p-Rb) in tumor tissue, in correlation with tumor response. | Data was reported in individual participant listings and not summarized due to change in planned analysis, where baseline and post-baseline tumor biopsies for biomarkers were no longer required and were not obtained for all participants. | Posted | Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93) |
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| 3 |
| 3 |
| 3 |
| 3 |
| EG001 | PD 0332991 50 mg QD (21/28 Days) | PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 1 | 3 | 3 | 3 |
| EG002 | PD 0332991 75 mg QD (21/28 Days) | PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 3 | 7 | 7 | 7 |
| EG003 | PD 0332991 100 mg QD (21/28 Days) | PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 1 | 3 | 3 | 3 |
| EG004 | PD 0332991 125 mg QD (21/28 Days) | PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 3 | 22 | 22 | 22 |
| EG005 | PD 0332991 150 mg QD (21/28 Days) | PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 0 | 3 | 3 | 3 |
| EG006 | PD 0332991 100 mg QD (14/21 Days) | PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 2 | 3 | 3 | 3 |
| EG007 | PD 0332991 150 mg QD (14/21 Days) | PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 3 | 4 | 4 | 4 |
| EG008 | PD 0332991 200 mg QD (14/21 Days) | PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 4 | 20 | 20 | 20 |
| EG009 | PD 0332991 225 mg QD (14/21 Days) | PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study. | 1 | 6 | 6 | 6 |
| Atrial fibrillation | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Oesophageal stenosis | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Chest pain | General disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Disease progression | General disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Jaundice | Hepatobiliary disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Weight decreased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
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| Hip arthroplasty | Surgical and medical procedures | MedDRA 11.1 | Non-systematic Assessment |
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| Stent placement | Surgical and medical procedures | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Alveolitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemoglobin | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Extrasystoles | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mitral valve prolapse | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Middle ear disorder | Ear and labyrinth disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Middle ear effusion | Ear and labyrinth disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Cushing's syndrome | Endocrine disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Change of bowel habit | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Oesophageal pain | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Tooth disorder | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Catheter site erythema | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Early satiety | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Face oedema | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Irritability | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Local swelling | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Peripheral coldness | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Ulcer | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Kidney infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Oral fungal infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Feeding tube complication | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Breath sounds abnormal | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Chest X-ray abnormal | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Electrocardiogram T wave inversion | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemoglobin | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Liver palpable subcostal | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Platelet count | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Waist circumference increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| White blood cell count | Investigations | MedDRA 11.1 | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Kyphosis | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Metastatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Non-systematic Assessment |
|
| Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypogeusia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyporeflexia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nervous system disorder | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Mood swings | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Bladder spasm | Renal and urinary disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Polyuria | Renal and urinary disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Amenorrhoea | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pelvic discomfort | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nasal mucosal disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Orthopnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pharyngeal lesion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Rhinalgia | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Onychomalacia | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Skin striae | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Cast application | Surgical and medical procedures | MedDRA 11.1 | Non-systematic Assessment |
|
| Sinus operation | Surgical and medical procedures | MedDRA 11.1 | Non-systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA 11.1 | Non-systematic Assessment |
|
| Diastolic hypertension | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hyperaemia | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 11.1 | Non-systematic Assessment |
|
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.
| D006425 |
| Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Non-Hematologic DLT: Grade 3 |
|
| Non-Hematologic DLT: Grade 4 |
|
| Non-Hematologic DLT: Grade 5 |
|
| Cycle 1 TEAEs: Grade 2 |
|
| Cycle 1 TEAEs: Grade 3 |
|
| Cycle 1 TEAEs: Grade 4 |
|
| Cycle 1 TEAEs: Grade 5 |
|
| Post Cycle 1 TEAEs: Grade 1 |
|
| Post Cycle 1 TEAEs: Grade 2 |
|
| Post Cycle 1 TEAEs: Grade 3 |
|
| Post Cycle 1 TEAEs: Grade 4 |
|
| Post Cycle 1 TEAEs: Grade 5 |
|
| Post Cycle 1 |
|
| Not Related to Study Drug |
|
| Confirmed PR |
|
| SD >=2 Cycles |
|
| SD >=4 Cycles |
|
| SD >=10 Cycles |
|
| PD |
|
| Not Assessable |
|