A Study Of Oral Palbociclib (PD-0332991), A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00141297
• Collaborator: (none)
• Enrollment: 74
• Locations: 4
• Arm: 1
• Duration (Months): 123
• Patients Per Site: 18.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms; Lymphoma, Non-Hodgkin	Drug: PD-0332991	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Clinical, Pharmacokinetic, And Pharmacodynamic Evaluation Of 2 Schedules Of Oral PD 0332991, A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-0332991	Drug: PD-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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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).

8. 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)]

9. 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)]

10. 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.

11. 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.

12. 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)]

13. 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)]

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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).

21. 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).

22. 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.

23. 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.

24. 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.

25. 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 - ∞).

26. 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 - ∞).

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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]).

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	Abramson Cancer Center Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
4	Pharmacy/PCAM/West Pavillion	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00141297
• Other Study ID Numbers: A5481001
• First Posted: Sep 1, 2005
• Last Update Posted: Jan 5, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Pfizer: Advanced cancer
• Additional relevant MeSH terms: Lymphoma, Non-Hodgkin; Palbociclib

Study Results

Participant Flow

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Period Title: Overall Study
STARTED	3	3	7	3	22	3	3	4	20	6
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	3	3	7	3	22	3	3	4	20	6

Baseline Characteristics

Arm/Group Title	PD 0332991 (21/28 Days)	PD 0332991 (14/21 Days)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	41	33	74
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (13.1)	59.9 (11.5)	56.5 (12.7)
Sex: Female, Male (Count of Participants)
Female	21 51.2%	17 51.5%	38 51.4%
Male	20 48.8%	16 48.5%	36 48.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicities (DLT)
Description	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

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	3	22	3	3	4	20	6
Number [participants]	0 0%	0 0%	2 2.7%	0 NaN	1 NaN	2 NaN	0 NaN	0 NaN	4 NaN	3 NaN

2. Primary Outcome

Title	Maximum Administered Dose (MAD)
Description	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

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 (21/28 Days)	PD 0332991 (14/21 Days)
Arm/Group Description	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.	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.
Measure Participants	41	33
Number [milligram]	150	225

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D)
Description	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

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 (21/28 Days)	PD 0332991 (14/21 Days)
Arm/Group Description	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.	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.
Measure Participants	41	33
Number [milligram]	125	200

4. Primary Outcome

Title	Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature
Description	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

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	3	22	3	3	4	20	6
Hematologic DLT: Grade 4	0	0	1	0	1	1	0	0	0	1
Non-Hematologic DLT: Grade 3	0	0	2	0	5	0	0	0	3	1
Non-Hematologic DLT: Grade 4	0	0	0	0	0	0	0	1	0	1
Non-Hematologic DLT: Grade 5	0	0	0	0	0	0	1	0	0	0

5. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events Categorized by Severity
Description	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)

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	3	22	3	3	4	20	6
Cycle 1 TEAEs: Grade 1	0 0%	2 6.1%	1 1.4%	0 NaN	7 NaN	1 NaN	2 NaN	2 NaN	6 NaN	1 NaN
Cycle 1 TEAEs: Grade 2	1 2.4%	1 3%	2 2.7%	1 NaN	5 NaN	0 NaN	0 NaN	1 NaN	6 NaN	1 NaN
Cycle 1 TEAEs: Grade 3	0 0%	0 0%	3 4.1%	2 NaN	7 NaN	1 NaN	0 NaN	0 NaN	8 NaN	2 NaN
Cycle 1 TEAEs: Grade 4	0 0%	0 0%	1 1.4%	0 NaN	1 NaN	1 NaN	0 NaN	1 NaN	0 NaN	1 NaN
Cycle 1 TEAEs: Grade 5	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Post Cycle 1 TEAEs: Grade 1	0 0%	0 0%	1 1.4%	0 NaN	8 NaN	0 NaN	0 NaN	1 NaN	3 NaN	1 NaN
Post Cycle 1 TEAEs: Grade 2	0 0%	3 9.1%	1 1.4%	2 NaN	3 NaN	1 NaN	1 NaN	1 NaN	4 NaN	1 NaN
Post Cycle 1 TEAEs: Grade 3	2 4.9%	0 0%	2 2.7%	0 NaN	3 NaN	2 NaN	1 NaN	1 NaN	8 NaN	3 NaN
Post Cycle 1 TEAEs: Grade 4	0 0%	0 0%	0 0%	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN
Post Cycle 1 TEAEs: Grade 5	1 2.4%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN

6. Primary Outcome

Title	Number of Participants With Treatment-Related Treatment Emergent Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	3	22	3	3	4	20	6
Cycle 1	0 0%	2 6.1%	5 6.8%	3 NaN	16 NaN	3 NaN	1 NaN	4 NaN	19 NaN	5 NaN
Post Cycle 1	1 2.4%	3 9.1%	4 5.4%	3 NaN	10 NaN	3 NaN	2 NaN	3 NaN	17 NaN	5 NaN

7. Primary Outcome

Title	Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug
Description	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)

Outcome Measure Data

Analysis Population Description

FAS included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	3	22	3	3	4	20	6
Related to Study Drug	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Not Related to Study Drug	1 2.4%	0 0%	0 0%	0 NaN	3 NaN	0 NaN	1 NaN	0 NaN	1 NaN	1 NaN

8. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set included all participants from FAS who had completed PK blood sampling for at least one day.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	6	22	7	20	6
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	9.6 (6.0)	20.7 (0.7)	28.7 (6.9)	45.6 (20.4)	51.6 (22.2)	83.8 (13.9)	80.8 (28.4)	104.2 (60.7)

9. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	6	6	13	6	8	6
Mean (Standard Deviation) [ng/mL]	15.9 (5.0)	35.7 (5.7)	58.6 (13.9)	71.2 (22.2)	86.2 (29.6)	160.8 (70.4)	173.6 (29.5)	185.7 (119.6)

10. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [ng/mL]	104.0 (50.2)

11. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	11
Fed	62.0 (20.4)
Fasted	44.9 (14.4)

12. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	6	22	7	20	6
Median (Full Range) [hours]	4.0	4.0	4.0	4.0	7.0	4.0	5.7	4.0

13. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	6	6	13	6	8	6
Median (Full Range) [hours]	4.0	4.1	4.0	5.5	4.0	7.0	4.0	4.5

14. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Median (Full Range) [hours]	4.2

15. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	11
Fed	7.00
Fasted	7.00

16. Primary Outcome

Title	Terminal Half-life (t½ ) on Day 1: Single Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

17. Primary Outcome

Title	Terminal Half-life (t½ ) on Day 8: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

18. Primary Outcome

Title	Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [hours]	26.5 (7.0)

19. Primary Outcome

Title	Terminal Half-life (t½ ) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

20. Primary Outcome

Title	Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose
Description	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)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants from FAS who had completed PK blood sampling for at least one day.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	7	6	22	7	20	6
Mean (Standard Deviation) [nanogram*hour/milliliter (ng*hour/mL)]	58 (29.5)	134 (7.2)	199 (40.5)	302 (119.6)	476 (281.1)	594 (118.1)	1057 (570.5)	719 (396.7)

21. Primary Outcome

Title	Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	6	6	13	6	8	6
Mean (Standard Deviation) [ng*hour/mL]	118 (38.3)	274 (41.8)	477 (122.7)	560 (183.1)	722 (265.3)	1344 (565.3)	1395 (315.6)	1482 (935.1)

22. Primary Outcome

Title	Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [ng*hour/mL]	3626 (2565.8)

23. Primary Outcome

Title	Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	11
Fed	809 (372.7)
Fasted	668 (280.6)

24. Primary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [ng*hour/mL]	1863 (1096.5)

25. Primary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single Dose
Description	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame	Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)

Outcome Measure Data

Analysis Population Description

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 - ∞).

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

26. Primary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple Dose
Description	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame	Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)

Outcome Measure Data

Analysis Population Description

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 - ∞).

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

27. Primary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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 - ∞).

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

28. Primary Outcome

Title	Apparent Oral Clearance (CL/F) on Day 1: Single Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

29. Primary Outcome

Title	Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

30. Primary Outcome

Title	Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [liter/hour]	86.1 (42.8)

31. Primary Outcome

Title	Apparent Oral Clearance (CL/F) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

32. Primary Outcome

Title	Apparent Volume of Distribution (Vz/F) on Day 1: Single Dose
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired 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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

33. Primary Outcome

Title	Apparent Volume of Distribution (Vz/F) on Day 8: Multiple Dose
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired 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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

34. Primary Outcome

Title	Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired 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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [liter]	3103 (1237.8)

35. Primary Outcome

Title	Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

36. Primary Outcome

Title	Accumulation Ratio (Rac) on Day 8: Multiple Dose
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

37. Primary Outcome

Title	Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [ratio]	2.5 (0.8)

38. Primary Outcome

Title	Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

39. Primary Outcome

Title	Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles . Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	Participants who received PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles and continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0

40. Primary Outcome

Title	Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	13
Mean (Standard Deviation) [1/hour]	0.028 (0.0)

41. Primary Outcome

Title	Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

42. Primary Outcome

Title	Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 200 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	9	10
Mean (Standard Deviation) [microgram (mcg)]	2191 (1404)	3171 (2442)

43. Primary Outcome

Title	Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

44. Primary Outcome

Title	Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 200 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	9	10
Mean (Standard Deviation) [percentage of dose]	1.75 (1.1)	1.59 (1.2)

45. Primary Outcome

Title	Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected because urine PK was not planned to be analyzed by food effect, as per protocol.

Arm/Group Title	PD 0332991 200 mg (14/21 Days) and 125 mg (21/28 Days)
Arm/Group Description	Participants received PD 0332991 200 mg and 125 mg capsule orally once daily (QD), continuously for 14 days in 21-day cycles and continuously for 21 days in 28-day cycles, respectively. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0

46. Primary Outcome

Title	Number of Participants With Best Response
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	3	3	6	3	20	2	3	3	19	6
Confirmed CR	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Confirmed PR	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	0 NaN
SD >=2 Cycles	1 2.4%	2 6.1%	1 1.4%	1 NaN	6 NaN	2 NaN	1 NaN	0 NaN	5 NaN	3 NaN
SD >=4 Cycles	1 2.4%	2 6.1%	1 1.4%	1 NaN	3 NaN	2 NaN	1 NaN	0 NaN	3 NaN	2 NaN
SD >=10 Cycles	0 0%	1 3%	1 1.4%	1 NaN	1 NaN	2 NaN	1 NaN	0 NaN	1 NaN	1 NaN
PD	2 4.9%	1 3%	6 8.1%	2 NaN	13 NaN	0 NaN	2 NaN	3 NaN	12 NaN	3 NaN
Not Assessable	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN

47. Primary Outcome

Title	Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0	0	0

48. Primary Outcome

Title	Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0	0	0

49. Primary Outcome

Title	Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0	0	0

50. Primary Outcome

Title	Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)	PD 0332991 50 mg QD (21/28 Days)	PD 0332991 75 mg QD (21/28 Days)	PD 0332991 100 mg QD (21/28 Days)	PD 0332991 125 mg QD (21/28 Days)	PD 0332991 150 mg QD (21/28 Days)	PD 0332991 100 mg QD (14/21 Days)	PD 0332991 150 mg QD (14/21 Days)	PD 0332991 200 mg QD (14/21 Days)	PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.	PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
Measure Participants	0	0	0	0	0	0	0	0	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	PD 0332991 25 mg QD (21/28 Days)		PD 0332991 50 mg QD (21/28 Days)		PD 0332991 75 mg QD (21/28 Days)		PD 0332991 100 mg QD (21/28 Days)		PD 0332991 125 mg QD (21/28 Days)		PD 0332991 150 mg QD (21/28 Days)		PD 0332991 100 mg QD (14/21 Days)		PD 0332991 150 mg QD (14/21 Days)		PD 0332991 200 mg QD (14/21 Days)		PD 0332991 225 mg QD (14/21 Days)
Arm/Group Description	PD 0332991 25 milligram (mg) capsule orally once daily (QD), continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 50 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 75 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 100 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 125 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 150 mg capsule orally QD, continuously for 21 days in 28-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 100 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 150 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 200 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.		PD 0332991 225 mg capsule orally QD, continuously for 14 days in 21-day cycles. Treatment cycles were repeated until occurrence of disease progression, unacceptable toxicity, or investigator/participant decision to withdraw from study.
All Cause Mortality
	PD 0332991 25 mg QD (21/28 Days)		PD 0332991 50 mg QD (21/28 Days)		PD 0332991 75 mg QD (21/28 Days)		PD 0332991 100 mg QD (21/28 Days)		PD 0332991 125 mg QD (21/28 Days)		PD 0332991 150 mg QD (21/28 Days)		PD 0332991 100 mg QD (14/21 Days)		PD 0332991 150 mg QD (14/21 Days)		PD 0332991 200 mg QD (14/21 Days)		PD 0332991 225 mg QD (14/21 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PD 0332991 25 mg QD (21/28 Days)		PD 0332991 50 mg QD (21/28 Days)		PD 0332991 75 mg QD (21/28 Days)		PD 0332991 100 mg QD (21/28 Days)		PD 0332991 125 mg QD (21/28 Days)		PD 0332991 150 mg QD (21/28 Days)		PD 0332991 100 mg QD (14/21 Days)		PD 0332991 150 mg QD (14/21 Days)		PD 0332991 200 mg QD (14/21 Days)		PD 0332991 225 mg QD (14/21 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		1/3 (33.3%)		3/7 (42.9%)		1/3 (33.3%)		3/22 (13.6%)		0/3 (0%)		2/3 (66.7%)		3/4 (75%)		4/20 (20%)		1/6 (16.7%)
Blood and lymphatic system disorders
Anaemia	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Cardiac disorders
Atrial fibrillation	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Cardiac arrest	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Palpitations	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Sinus bradycardia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Supraventricular tachycardia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Constipation	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Dysphagia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Gastrointestinal haemorrhage	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Intestinal obstruction	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Nausea	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Oesophageal stenosis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Small intestinal obstruction	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Vomiting	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/20 (5%)		0/6 (0%)
General disorders
Chest pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Disease progression	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Pyrexia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Jaundice	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Investigations
Weight decreased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Haemoglobin	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Dehydration	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Failure to thrive	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Renal and urinary disorders
Renal failure acute	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pulmonary embolism	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Alveolitis allergic	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Surgical and medical procedures
Hip arthroplasty	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Stent placement	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Vascular disorders
Hypertension	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Hypotension	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		2/4 (50%)		0/20 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	PD 0332991 25 mg QD (21/28 Days)		PD 0332991 50 mg QD (21/28 Days)		PD 0332991 75 mg QD (21/28 Days)		PD 0332991 100 mg QD (21/28 Days)		PD 0332991 125 mg QD (21/28 Days)		PD 0332991 150 mg QD (21/28 Days)		PD 0332991 100 mg QD (14/21 Days)		PD 0332991 150 mg QD (14/21 Days)		PD 0332991 200 mg QD (14/21 Days)		PD 0332991 225 mg QD (14/21 Days)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		7/7 (100%)		3/3 (100%)		22/22 (100%)		3/3 (100%)		3/3 (100%)		4/4 (100%)		20/20 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)		0/3 (0%)		2/7 (28.6%)		1/3 (33.3%)		6/22 (27.3%)		1/3 (33.3%)		1/3 (33.3%)		1/4 (25%)		8/20 (40%)		3/6 (50%)
Leukopenia	0/3 (0%)		0/3 (0%)		0/7 (0%)		2/3 (66.7%)		2/22 (9.1%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		3/20 (15%)		2/6 (33.3%)
Neutropenia	0/3 (0%)		2/3 (66.7%)		4/7 (57.1%)		3/3 (100%)		8/22 (36.4%)		3/3 (100%)		0/3 (0%)		0/4 (0%)		12/20 (60%)		3/6 (50%)
Thrombocytopenia	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		3/22 (13.6%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		5/20 (25%)		2/6 (33.3%)
Cardiac disorders
Arrhythmia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Extrasystoles	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Mitral valve prolapse	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Palpitations	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Sinus tachycardia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Supraventricular extrasystoles	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Supraventricular tachycardia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Tachycardia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Ear and labyrinth disorders
Ear discomfort	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Middle ear disorder	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Middle ear effusion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Vertigo	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Endocrine disorders
Cushing's syndrome	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Eye disorders
Conjunctivitis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Dry eye	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Vision blurred	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Abdominal distension	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Abdominal pain	0/3 (0%)		1/3 (33.3%)		2/7 (28.6%)		1/3 (33.3%)		4/22 (18.2%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Abdominal pain lower	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Abdominal pain upper	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Abdominal tenderness	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Change of bowel habit	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Constipation	0/3 (0%)		2/3 (66.7%)		2/7 (28.6%)		1/3 (33.3%)		5/22 (22.7%)		0/3 (0%)		2/3 (66.7%)		2/4 (50%)		6/20 (30%)		1/6 (16.7%)
Diarrhoea	0/3 (0%)		2/3 (66.7%)		3/7 (42.9%)		1/3 (33.3%)		4/22 (18.2%)		0/3 (0%)		2/3 (66.7%)		1/4 (25%)		9/20 (45%)		2/6 (33.3%)
Dry mouth	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		1/3 (33.3%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Dyspepsia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Dysphagia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Flatulence	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		2/3 (66.7%)		2/22 (9.1%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		3/20 (15%)		0/6 (0%)
Frequent bowel movements	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Gastrooesophageal reflux disease	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Gingival pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Haemorrhoidal haemorrhage	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Mouth ulceration	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Nausea	0/3 (0%)		2/3 (66.7%)		2/7 (28.6%)		2/3 (66.7%)		6/22 (27.3%)		2/3 (66.7%)		1/3 (33.3%)		1/4 (25%)		11/20 (55%)		1/6 (16.7%)
Oesophageal pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Oral pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Retching	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Stomatitis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Tooth disorder	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Vomiting	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		2/3 (66.7%)		6/22 (27.3%)		1/3 (33.3%)		1/3 (33.3%)		1/4 (25%)		3/20 (15%)		0/6 (0%)
General disorders
Asthenia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Catheter site erythema	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Chest discomfort	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Chest pain	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Chills	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		1/4 (25%)		2/20 (10%)		0/6 (0%)
Early satiety	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Face oedema	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Fatigue	1/3 (33.3%)		2/3 (66.7%)		3/7 (42.9%)		2/3 (66.7%)		10/22 (45.5%)		3/3 (100%)		2/3 (66.7%)		1/4 (25%)		15/20 (75%)		3/6 (50%)
Gait disturbance	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Influenza like illness	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Irritability	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Local swelling	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Mucosal inflammation	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		1/6 (16.7%)
Oedema	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Oedema peripheral	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		1/22 (4.5%)		0/3 (0%)		1/3 (33.3%)		2/4 (50%)		4/20 (20%)		0/6 (0%)
Pain	0/3 (0%)		3/3 (100%)		1/7 (14.3%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		4/20 (20%)		0/6 (0%)
Peripheral coldness	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Pyrexia	1/3 (33.3%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/4 (25%)		2/20 (10%)		0/6 (0%)
Ulcer	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		3/22 (13.6%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Infections and infestations
Bacteraemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Bronchitis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Cellulitis	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Fungal skin infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Gastroenteritis viral	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Gastrointestinal infection	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Kidney infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Localised infection	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Nasopharyngitis	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Oral candidiasis	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Oral fungal infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Oral herpes	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Otitis media	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pneumonia	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Sinusitis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Tooth abscess	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Tooth infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Upper respiratory tract infection	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Urinary tract infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Viral infection	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
Contusion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Fall	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Feeding tube complication	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Incision site pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Post procedural haemorrhage	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Wound dehiscence	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Aspartate aminotransferase increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Blood alkaline phosphatase	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Blood alkaline phosphatase increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Blood creatinine increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Blood pressure increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Blood uric acid increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Breath sounds abnormal	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Chest X-ray abnormal	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Electrocardiogram QT prolonged	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Electrocardiogram T wave inversion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Haemoglobin	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Haemoglobin decreased	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Liver palpable subcostal	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Platelet count	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Platelet count decreased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Waist circumference increased	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Weight decreased	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
White blood cell count	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Metabolism and nutrition disorders
Anorexia	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		4/22 (18.2%)		0/3 (0%)		2/3 (66.7%)		1/4 (25%)		3/20 (15%)		0/6 (0%)
Cachexia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Decreased appetite	1/3 (33.3%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		2/4 (50%)		2/20 (10%)		0/6 (0%)
Dehydration	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Hyperglycaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/20 (5%)		0/6 (0%)
Hypoalbuminaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Hypokalaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Hyponatraemia	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		1/3 (33.3%)		2/22 (9.1%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		2/6 (33.3%)
Back pain	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		1/3 (33.3%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		2/20 (10%)		2/6 (33.3%)
Flank pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		3/20 (15%)		0/6 (0%)
Intervertebral disc disorder	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Kyphosis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Limb discomfort	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Muscle spasms	0/3 (0%)		0/3 (0%)		0/7 (0%)		2/3 (66.7%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		3/20 (15%)		0/6 (0%)
Muscular weakness	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Musculoskeletal chest pain	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Musculoskeletal pain	0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Musculoskeletal stiffness	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Myalgia	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Neck pain	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Pain in extremity	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Neoplasm	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Nervous system disorders
Dizziness	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Dysgeusia	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		1/22 (4.5%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		1/20 (5%)		0/6 (0%)
Headache	0/3 (0%)		1/3 (33.3%)		2/7 (28.6%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Hypoaesthesia	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		3/20 (15%)		0/6 (0%)
Hypogeusia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Hyporeflexia	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Loss of consciousness	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Nervous system disorder	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Paraesthesia	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Parosmia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Peripheral sensory neuropathy	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Sensory disturbance	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Somnolence	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Tremor	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Psychiatric disorders
Agitation	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Anxiety	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Confusional state	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/20 (5%)		0/6 (0%)
Depression	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Disorientation	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Insomnia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		4/22 (18.2%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Mental status changes	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Mood altered	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Mood swings	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Renal and urinary disorders
Bladder spasm	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Micturition urgency	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pollakiuria	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Polyuria	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Reproductive system and breast disorders
Amenorrhoea	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Dysmenorrhoea	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Erectile dysfunction	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Menorrhagia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pelvic discomfort	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Vulvovaginal dryness	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Cough	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		2/22 (9.1%)		1/3 (33.3%)		2/3 (66.7%)		0/4 (0%)		3/20 (15%)		1/6 (16.7%)
Dysphonia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Dyspnoea	2/3 (66.7%)		0/3 (0%)		1/7 (14.3%)		1/3 (33.3%)		4/22 (18.2%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		4/20 (20%)		2/6 (33.3%)
Dyspnoea exertional	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Epistaxis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		4/20 (20%)		0/6 (0%)
Haemoptysis	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hypoxia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Nasal congestion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Nasal discomfort	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Nasal mucosal disorder	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Oropharyngeal pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		1/3 (33.3%)		0/3 (0%)		1/4 (25%)		2/20 (10%)		0/6 (0%)
Orthopnoea	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Pharyngeal erythema	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pharyngeal lesion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pleural effusion	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Pleuritic pain	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Postnasal drip	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Productive cough	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/20 (5%)		0/6 (0%)
Pulmonary congestion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Rhinalgia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Rhinorrhoea	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		1/20 (5%)		2/6 (33.3%)
Rhonchi	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		2/3 (66.7%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Sinus congestion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Throat irritation	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Upper respiratory tract congestion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Wheezing	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/3 (33.3%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		2/22 (9.1%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Dermatitis acneiform	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Dry skin	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		1/6 (16.7%)
Erythema	1/3 (33.3%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Hair growth abnormal	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hyperhidrosis	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		1/6 (16.7%)
Nail discolouration	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Night sweats	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		1/6 (16.7%)
Onychomalacia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		1/22 (4.5%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Petechiae	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Pruritus	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		2/20 (10%)		0/6 (0%)
Rash	0/3 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		1/22 (4.5%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		4/20 (20%)		2/6 (33.3%)
Skin disorder	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Skin lesion	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Skin striae	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Urticaria	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Surgical and medical procedures
Cast application	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Sinus operation	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Tooth extraction	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Vascular disorders
Diastolic hypertension	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		1/6 (16.7%)
Flushing	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/20 (0%)		0/6 (0%)
Haemorrhage	0/3 (0%)		1/3 (33.3%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hyperaemia	0/3 (0%)		0/3 (0%)		0/7 (0%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/20 (0%)		0/6 (0%)
Hypertension	0/3 (0%)		0/3 (0%)		0/7 (0%)		1/3 (33.3%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/20 (5%)		0/6 (0%)
Orthostatic hypotension	1/3 (33.3%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/22 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/20 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.