Lymphoma, Non-Hodgkin, Neoplasms
Conditions
Keywords
Advanced cancer
Brief summary
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.
Interventions
DRUGPD-0332991
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
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced solid tumors (excluding SCLC and retinoblastoma) or follicular of diffuse large cell non-Hodgkin's lymphoma, histologically or cytologically proven at diagnosis which is refractory to or intolerant of established therapy know to provide clinical benefit for their condition; tumors must express Rb * Adequate blood cell counts, kidney function and liver function and and ECOG score of 0, 1, or 2. * Patients may have to have tumor biopsy before and after treatment.
Exclusion criteria
* Prior stem cell or bone marrow transplant * Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse * Active or unstable cardiac disease or history of heart attack within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLT) | Baseline up to 28 days | 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. |
| Maximum Administered Dose (MAD) | Baseline up to 28 days | 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. |
| Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D) | Baseline up to 28 days | 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. |
| Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Baseline up to 28 days | 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. |
| Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) | 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. |
| Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93) | 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. |
| Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Baseline up to 30 days after end of treatment (up to Cycle 93) | 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). |
| 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 | 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) | 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. |
| Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| 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 | 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) | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Terminal Half-life (t½ ) 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) | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| Terminal Half-life (t½ ) 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) | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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 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. |
| Terminal Half-life (t½ ) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) 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) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) 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) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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 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. |
| Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| 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 | 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 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. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] 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) | 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 - ∞). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] 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) | 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 - ∞). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Apparent Oral Clearance (CL/F) 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) | 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. |
| Apparent Oral Clearance (CL/F) 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) | 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. |
| Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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) | 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. |
| Apparent Oral Clearance (CL/F) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Apparent Volume of Distribution (Vz/F) 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) | 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. |
| Apparent Volume of Distribution (Vz/F) 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) | 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. |
| Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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) | 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. |
| Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Accumulation Ratio (Rac) on Day 8: Multiple Dose | Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8 | Rac at Day 8 = AUC (0-tau) at Day 8 divided by AUC (0-tau) at Day 1. |
| Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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) | 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. |
| Terminal Phase Rate Constant [Lambda (z)] 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) | 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. |
| Terminal Phase Rate Constant [Lambda (z)] 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) | 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. |
| Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 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 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. |
| Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect | Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1 | 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. |
| Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 | 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 \[14/21 Days\]). |
| Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 | 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. |
| Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 | 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. |
| Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect | Hour 0 (pre-dose) to 10 hours post-dose on C1D1 | 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. |
| Number of Participants With Best 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) | 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. |
| Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue | 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) | 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. |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With 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) | 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. |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With 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) | 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. |
| Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 41 |
| 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. | 33 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 5 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Progressive Disease | 2 | 3 | 6 | 2 | 15 | 2 | 3 | 3 | 15 | 6 |
| Overall Study | Transitioned | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PD 0332991 (21/28 Days) | PD 0332991 (14/21 Days) | Total |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 13.1 | 59.9 years STANDARD_DEVIATION 11.5 | 56.5 years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 21 Participants | 17 Participants | 38 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 7 / 7 | 3 / 3 | 22 / 22 | 3 / 3 | 3 / 3 | 4 / 4 | 20 / 20 | 6 / 6 |
| serious Total, serious adverse events | 3 / 3 | 1 / 3 | 3 / 7 | 1 / 3 | 3 / 22 | 0 / 3 | 2 / 3 | 3 / 4 | 4 / 20 | 1 / 6 |
Outcome results
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 2.5 ratio | Standard Deviation 0.8 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 86.1 liter/hour | Standard Deviation 42.8 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 3103 liter | Standard Deviation 1237.8 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | 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 | 1863 ng*hour/mL | Standard Deviation 1096.5 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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 - ∞).
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 - ∞).
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: 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 - ∞).
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 - ∞).
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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 - ∞).
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 3626 ng*hour/mL | Standard Deviation 2565.8 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect | Fed | 809 ng*hour/mL | Standard Deviation 372.7 |
| PD 0332991 25 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect | Fasted | 668 ng*hour/mL | Standard Deviation 280.6 |
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).
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 58 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 29.5 |
| PD 0332991 50 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 134 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 7.2 |
| PD 0332991 75 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 199 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 40.5 |
| PD 0332991 100 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 302 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 119.6 |
| PD 0332991 125 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 476 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 281.1 |
| PD 0332991 150 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 594 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 118.1 |
| PD 0332991 100 mg QD (14/21 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 1057 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 570.5 |
| PD 0332991 150 mg QD (14/21 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose | 719 nanogram*hour/milliliter (ng*hour/mL) | Standard Deviation 396.7 |
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).
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 118 ng*hour/mL | Standard Deviation 38.3 |
| PD 0332991 50 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 274 ng*hour/mL | Standard Deviation 41.8 |
| PD 0332991 75 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 477 ng*hour/mL | Standard Deviation 122.7 |
| PD 0332991 100 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 560 ng*hour/mL | Standard Deviation 183.1 |
| PD 0332991 125 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 722 ng*hour/mL | Standard Deviation 265.3 |
| PD 0332991 150 mg QD (21/28 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 1344 ng*hour/mL | Standard Deviation 565.3 |
| PD 0332991 100 mg QD (14/21 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 1395 ng*hour/mL | Standard Deviation 315.6 |
| PD 0332991 150 mg QD (14/21 Days) | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose | 1482 ng*hour/mL | Standard Deviation 935.1 |
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.
Time frame: 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)
Population: 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.
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.
Time frame: 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)
Population: 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.
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.
Time frame: 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)
Population: 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.
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.
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Population: Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol.
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 \[14/21 Days\]).
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose | 2191 microgram (mcg) | Standard Deviation 1404 |
| PD 0332991 50 mg QD (21/28 Days) | Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose | 3171 microgram (mcg) | Standard Deviation 2442 |
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.
Time frame: 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)
Population: 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.
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.
Time frame: Baseline up to 28 days
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Administered Dose (MAD) | 150 milligram |
| PD 0332991 50 mg QD (21/28 Days) | Maximum Administered Dose (MAD) | 225 milligram |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 104.0 ng/mL | Standard Deviation 50.2 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect | Fed | 62.0 ng/mL | Standard Deviation 20.4 |
| PD 0332991 25 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect | Fasted | 44.9 ng/mL | Standard Deviation 14.4 |
Primary
Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: Pharmacokinetic (PK) analysis set included all participants from FAS who had completed PK blood sampling for at least one day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 9.6 nanogram per milliliter (ng/mL) | Standard Deviation 6 |
| PD 0332991 50 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 20.7 nanogram per milliliter (ng/mL) | Standard Deviation 0.7 |
| PD 0332991 75 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 28.7 nanogram per milliliter (ng/mL) | Standard Deviation 6.9 |
| PD 0332991 100 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 45.6 nanogram per milliliter (ng/mL) | Standard Deviation 20.4 |
| PD 0332991 125 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 51.6 nanogram per milliliter (ng/mL) | Standard Deviation 22.2 |
| PD 0332991 150 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 83.8 nanogram per milliliter (ng/mL) | Standard Deviation 13.9 |
| PD 0332991 100 mg QD (14/21 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 80.8 nanogram per milliliter (ng/mL) | Standard Deviation 28.4 |
| PD 0332991 150 mg QD (14/21 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose | 104.2 nanogram per milliliter (ng/mL) | Standard Deviation 60.7 |
Primary
Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 15.9 ng/mL | Standard Deviation 5 |
| PD 0332991 50 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 35.7 ng/mL | Standard Deviation 5.7 |
| PD 0332991 75 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 58.6 ng/mL | Standard Deviation 13.9 |
| PD 0332991 100 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 71.2 ng/mL | Standard Deviation 22.2 |
| PD 0332991 125 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 86.2 ng/mL | Standard Deviation 29.6 |
| PD 0332991 150 mg QD (21/28 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 160.8 ng/mL | Standard Deviation 70.4 |
| PD 0332991 100 mg QD (14/21 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 173.6 ng/mL | Standard Deviation 29.5 |
| PD 0332991 150 mg QD (14/21 Days) | Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose | 185.7 ng/mL | Standard Deviation 119.6 |
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.
Time frame: Baseline up to 28 days
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D) | 125 milligram |
| PD 0332991 50 mg QD (21/28 Days) | Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D) | 200 milligram |
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.
Time frame: Baseline up to 28 days
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 25 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 25 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 25 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 50 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 50 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 50 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 50 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 75 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 75 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 75 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 1 DLTs |
| PD 0332991 75 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 2 DLTs |
| PD 0332991 100 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 100 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 100 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 100 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 125 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 5 DLTs |
| PD 0332991 125 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 1 DLTs |
| PD 0332991 125 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 125 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 150 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 1 DLTs |
| PD 0332991 150 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 150 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 150 mg QD (21/28 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 100 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 1 DLTs |
| PD 0332991 100 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 100 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 100 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 150 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 1 DLTs |
| PD 0332991 150 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 150 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 0 DLTs |
| PD 0332991 150 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 200 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 200 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 3 DLTs |
| PD 0332991 200 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 0 DLTs |
| PD 0332991 200 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 225 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 5 | 0 DLTs |
| PD 0332991 225 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Hematologic DLT: Grade 4 | 1 DLTs |
| PD 0332991 225 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 3 | 1 DLTs |
| PD 0332991 225 mg QD (14/21 Days) | Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature | Non-Hematologic DLT: Grade 4 | 1 DLTs |
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).
Time frame: Baseline up to 30 days after end of treatment (up to Cycle 93)
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 1 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 3 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Related to Study Drug | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug | Not Related to Study Drug | 1 participants |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 2 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 1 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 1 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 1 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 2 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 2 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 6 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 1 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 2 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 1 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 1 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 13 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 6 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 3 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=2 Cycles | 2 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | PD | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=10 Cycles | 2 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | SD >=4 Cycles | 2 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=4 Cycles | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=2 Cycles | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Best Response | PD | 2 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=2 Cycles | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | PD | 3 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=10 Cycles | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=4 Cycles | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | Not Assessable | 1 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=2 Cycles | 5 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=4 Cycles | 3 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | PD | 12 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed PR | 2 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=10 Cycles | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed CR | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | Confirmed PR | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=4 Cycles | 2 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | SD >=2 Cycles | 3 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | PD | 3 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Best Response | Not Assessable | 0 participants |
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.
Time frame: Baseline up to 28 days
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 2 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 1 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 2 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 4 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Dose-Limiting Toxicities (DLT) | 3 participants |
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.
Time frame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 1 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 2 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 2 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 3 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 2 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 3 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 2 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 2 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 2 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 5 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 8 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 7 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 3 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 3 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 7 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 1 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 2 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 2 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 2 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 1 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 6 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 3 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 6 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 4 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 8 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 8 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 4 | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 3 | 3 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Post Cycle 1 TEAEs: Grade 1 | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 5 | 0 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 4 | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 2 | 1 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment Emergent Adverse Events Categorized by Severity | Cycle 1 TEAEs: Grade 3 | 2 participants |
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.
Time frame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
Population: FAS included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 1 participants |
| PD 0332991 25 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 0 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 3 participants |
| PD 0332991 50 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 2 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 5 participants |
| PD 0332991 75 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 4 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 3 participants |
| PD 0332991 100 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 3 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 10 participants |
| PD 0332991 125 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 16 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 3 participants |
| PD 0332991 150 mg QD (21/28 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 3 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 2 participants |
| PD 0332991 100 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 1 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 4 participants |
| PD 0332991 150 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 3 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 19 participants |
| PD 0332991 200 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 17 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Post Cycle 1 | 5 participants |
| PD 0332991 225 mg QD (14/21 Days) | Number of Participants With Treatment-Related Treatment Emergent Adverse Events | Cycle 1 | 5 participants |
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.
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose | 1.75 percentage of dose | Standard Deviation 1.1 |
| PD 0332991 50 mg QD (21/28 Days) | Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose | 1.59 percentage of dose | Standard Deviation 1.2 |
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.
Time frame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
Population: Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 26.5 hours | Standard Deviation 7 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 0.028 1/hour | Standard Deviation 0 |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: 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
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose | 4.2 hours |
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.
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect | Fed | 7.00 hours |
| PD 0332991 25 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect | Fasted | 7.00 hours |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
Population: PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
| PD 0332991 50 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
| PD 0332991 75 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
| PD 0332991 100 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
| PD 0332991 125 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 7.0 hours |
| PD 0332991 150 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
| PD 0332991 100 mg QD (14/21 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 5.7 hours |
| PD 0332991 150 mg QD (14/21 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose | 4.0 hours |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose
Time frame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PD 0332991 25 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.0 hours |
| PD 0332991 50 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.1 hours |
| PD 0332991 75 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.0 hours |
| PD 0332991 100 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 5.5 hours |
| PD 0332991 125 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.0 hours |
| PD 0332991 150 mg QD (21/28 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 7.0 hours |
| PD 0332991 100 mg QD (14/21 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.0 hours |
| PD 0332991 150 mg QD (14/21 Days) | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose | 4.5 hours |