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Palbociclib Pharmacokinetics Study In Postmenopausal Chinese Women With ER (+), HER2 (-) Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02499146
Recruitment Status : Unknown
Verified May 2019 by Pfizer.
Recruitment status was:  Active, not recruiting
First Posted : July 15, 2015
Results First Posted : July 29, 2019
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Masking: None (Open Label);   Primary Purpose: Other
Condition Advanced Breast Cancer
Interventions Drug: Palbociclib
Drug: Letrozole
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Period Title: Overall Study
Started 26
Completed 0
Not Completed 26
Reason Not Completed
Lost to Follow-up             1
Withdrawal by Subject             1
Other             2
Ongoing at date of cut-off             9
Began other treatment/therapy             13
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
All enrolled participants who received at least 1 dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
50.8  (7.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
26
 100.0%
Male
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Asian
26
 100.0%
1.Primary Outcome
Title Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib
Hide Description Cmax of palbociclib in the single-dose part (lead-in phase) was observed directly from data.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
82.14
(25%)
2.Primary Outcome
Title Single-dose PK: Time to Reach Maximum Plasma Concentration (Tmax) for Palbociclib
Hide Description Tmax for palbociclib in the single-dose part (lead-in phase) was observed directly from data as time of first occurrence.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Median (Full Range)
Unit of Measure: hours
7.94
(3.97 to 10.0)
3.Primary Outcome
Title Single-dose PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Time 10 Hours (AUC10) for Palbociclib
Hide Description AUC10 for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, and 10 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hour per milliliter (ng*hr/mL)
498.3
(28%)
4.Primary Outcome
Title Single-dose PK: AUC From Time 0 to the Time 24 Hours (AUC24) for Palbociclib
Hide Description AUC24 is AUCtau, where the dosing interval (tau) is 24 hours. AUC24 in the single-dose part (lead-in phase) for palbociclib was obtained by linear/log trapezoidal method.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1217
(22%)
5.Primary Outcome
Title Single-dose PK: AUC From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Palbociclib
Hide Description AUClast for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
2308
(27%)
6.Primary Outcome
Title Single-dose PK: AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Palbociclib
Hide Description AUCinf for palbociclib in the single-dose part (lead-in phase) was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the rate constant for terminal phase obtained by linear regression of the log-linear concentration-time curve.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
2386
(27%)
7.Primary Outcome
Title Single-dose PK: Rate Constant for Terminal Phase (Kel) for Palbociclib
Hide Description Kel for palbociclibo in the single-dose part (lead-in phase) was obtained by linear regression of the log-linear concentration-time curve.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: per hour
0.03006  (0.00420)
8.Primary Outcome
Title Single-dose PK: Mean Residence Time (MRT) for Palbociclib
Hide Description MRT for palbociclib in the single-dose part (lead-in phase) was calculated as AUMCinf/AUCinf, where AUMCinf was area under the first moment curve from time 0 to infinity.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: hours
34.42  (4.32)
9.Primary Outcome
Title Single-dose PK: Terminal Half-Life (t1/2) for Palbociclib
Hide Description t1/2 for palbociclib in the single-dose part (lead-in phase) was calculated as Loge(2)/kel.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: hours
23.46  (3.14)
10.Primary Outcome
Title Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib
Hide Description CL/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/AUCinf.
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters per hour (L/hr)
52.40
(27%)
11.Primary Outcome
Title Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib
Hide Description Vz/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/(AUCinf * kel).
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters
1758
(21%)
12.Primary Outcome
Title Multiple-dose PK: Maximum Plasma Concentration at Steady State (Css,Max) for Palbociclib
Hide Description Css,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
139.7
(28%)
13.Primary Outcome
Title Multiple-dose PK: Minimum Plasma Concentration at Steady State (Css,Min) for Palbociclib
Hide Description Css,min of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
67.55
(46%)
14.Primary Outcome
Title Multiple-dose PK: AUC Within a Dosing Interval of Tau (=24 Hours) at Steady State (AUCss,Tau) for Palbociclib
Hide Description AUCss,tau of palbociclib in the multiple-dose part (Cycle 1) was determined by linear/log trapezoidal method.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
2501
(29%)
15.Primary Outcome
Title Multiple-dose PK: Average Plasma Concentration at Steady State (Css,av) for Palbociclib
Hide Description Css,av of palbociclib in the multiple-dose part (Cycle 1) was calculated as AUCss,tau/tau, where tau was 24 hours.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
104.2
(29%)
16.Primary Outcome
Title Multiple-dose PK: Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for Palbociclib
Hide Description Tss,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data as time of first occurrence within tau (=24 hours) at steady state.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Median (Full Range)
Unit of Measure: hours
6.05
(3.97 to 10.0)
17.Primary Outcome
Title Multiple-dose PK: Vz/F for Palbociclib
Hide Description Vz/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/(AUCss,tau * kel), where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state and kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest and a well characterized terminal phase in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
1910
(29%)
18.Primary Outcome
Title Multiple-dose PK: t1/2 for Palbociclib
Hide Description t1/2 of palbociclib in the multiple-dose part (Cycle 1) was calculated as ln (2)/kel, where kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest and a well characterized terminal phase in the multiple-dose part .
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: hours
27.26  (3.19)
19.Primary Outcome
Title Multiple-dose PK: CL/F for Palbociclib
Hide Description CL/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/AUCss,tau, where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
49.97
(29%)
20.Primary Outcome
Title Multiple-dose PK: Peak to Trough Fluctuation at Steady State (PTF) for Palbociclib
Hide Description PTF of palbociclib in the multiple-dose part (Cycle 1) was determined as (Css,max - Css,min)/Css,av. Css,max and Css,min were observed directly from data while Css,av was calculated as AUCss,tau/tau, where tau was 24 hours.
Time Frame Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.6652
(27%)
21.Primary Outcome
Title Observed Accumulation Ratio (Rac) for Palbociclib
Hide Description Rac of palbociclib was determined as AUCss,tau/AUCsd,tau, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCsd,tau was AUC24 from single-dose part (lead-in phase).
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose; Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose and multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
2.042
(27%)
22.Primary Outcome
Title Steady State Accumulation Ratio (Rss) for Palbociclib
Hide Description Rss of palbociclib was calcualted as AUCss,tau/AUCinf, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCinf was from single-dose part (lead-in phase).
Time Frame Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose; Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24 hours post dose on Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose and multiple-dose part.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.036
(26%)
23.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.
Time Frame From first dose of study medication up to 28 days after last dose (up to 2.8 years by primary completion date of 31 July 2018)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment-emergent AEs (all causalities)
26
 100.0%
Treatment-emergent AEs (treatment-related)
26
 100.0%
Treatment-emergent SAEs (all causalities)
2
   7.7%
Treatment-emergent SAEs (treatment-related)
1
   3.8%
24.Secondary Outcome
Title Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade
Hide Description Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by NCI CTCAE version 4.0: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame up to 2.8 years by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
0
   0.0%
Grade 2
5
  19.2%
Grade 3
17
  65.4%
Grade 4
4
  15.4%
Grade 5
0
   0.0%
25.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities
Hide Description The number of participants with the following laboratory test abnormalities meeting any of the Grades 1 to 4 criteria per the NCI CTCAE (version 4.0) was summarized: anemia, lymphopenia, neutropenia, platelet count decreased, white blood cell (WBC) decreased, alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, bilirubin (total) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia.
Time Frame up to 2.8 years by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia
22
  84.6%
Lymphopenia
19
  73.1%
Neutropenia
26
 100.0%
Platelet count decreased
19
  73.1%
WBC decreased
25
  96.2%
ALT increased
8
  30.8%
Alkaline phosphatase increased
12
  46.2%
AST increased
16
  61.5%
Bilirubin (total) increased
3
  11.5%
Creatinine increased
25
  96.2%
Hypercalcemia
0
   0.0%
Hyperglycemia
10
  38.5%
Hyperkalemia
0
   0.0%
Hypermagnesemia
2
   7.7%
Hypernatremia
6
  23.1%
Hypoalbuminemia
11
  42.3%
Hypocalcemia
11
  42.3%
Hypoglycemia
0
   0.0%
Hypokalemia
6
  23.1%
Hypomagnesemia
5
  19.2%
Hyponatremia
5
  19.2%
26.Secondary Outcome
Title Number of Participants Meeting the Categorical Summarization Criteria for QTcF and QTcB Parameters
Hide Description QT interval (time from electrocardiogram [ECG] Q wave to the end of the T wave corresponding to electrical systole) corrected for heart rate using Fridericia's formula was QTcF and QT interval corrected for heart rate using Bazett's formula was QTcB. Categorical summarization criteria for QTcF and QTcB were as follows: 1) maximum absolute value of <450 msec, 450 to 480 msec, 481 to 500 msec, or >=500 msec; 2) maximum increase from baseline of <30 msec, 30 to <60 msec, or >=60 msec.
Time Frame up to 2.8 years by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 dose of study medication.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum QTcF <450 msec
21
  80.8%
Maximum QTcF >=450 to <=480 msec
4
  15.4%
Maximum QTcF >=481 to <=500 msec
1
   3.8%
Maximum QTcF >500 msec
0
   0.0%
Maximum increase in QTcF <30 msec
17
  65.4%
Maximum increase in QTcF >=30 to <60 msec
9
  34.6%
Maximum increase in QTcF >=60 msec
0
   0.0%
Maximum QTcB <450 msec
10
  38.5%
Maximum QTcB >=450 to <=480 msec
15
  57.7%
Maximum QTcB >500 msec
1
   3.8%
Maximum QTcB >=481 to <=500 msec
0
   0.0%
Maximum increase in QTcB <30 msec
16
  61.5%
Maximum increase in QTcB >=30 to <60 msec
9
  34.6%
Maximum increase in QTcB >=60 msec
1
   3.8%
27.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1). Objective status of PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
Time Frame Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started the treatment of Cycle 1.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Median (95% Confidence Interval)
Unit of Measure: months
18.6
(6.5 to 27.7)
28.Secondary Outcome
Title Percentage of Participants Achieving Objective Response (Objective Response Rate [ORR])
Hide Description ORR was the percentage of participants with an objective response (complete response [CR] or partial response [PR]). Per RECIST (version 1.1), objective status of CR: target lesions and non-target diseases achieved CR, without new lesions; objective status of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Time Frame Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started the treatment of Cycle 1.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
19.2
(6.6 to 39.4)
29.Secondary Outcome
Title Percentage of Participants Achieving Disease Control (Disease Control Rate [DCR])
Hide Description DCR was the percentage of participants achieving disease control (CR, PR or stable disease [SD] >=24 weeks from Cycle 1 Day 1 to PD or death due to any cause). The definitions for objective status of CR, PR, and PD per RECIST (version 1.1) can be found in the previous Outcome Measures. Per RECIST (version 1.1), objective status of SD: target lesions achieved SD (i.e., did not qualify for CR, PR or PD) while non-target diseases were assessed as non-CR/non-PD, indeterminate or missing, and there were no new lesions.
Time Frame Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started the treatment of Cycle 1.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
65.4
(44.3 to 82.8)
30.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was the time from first documentation of CR or PR to date of first documentation of PD or death for the participants with an objective response (CR or PR). The definitions of CR, PR, and PD per RECIST (version 1.1) can be found in the previous Outcome Measures.
Time Frame Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started the treatment of Cycle 1 and achieved an objective response (CR or PR per RECIST version 1.1).
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 5
Median (95% Confidence Interval)
Unit of Measure: months
25.1 [1] 
(8.3 to NA)
[1]
The upper limit of 95% confidence interval (CI) was not estimable due to the small number of events.
31.Secondary Outcome
Title 1-Year PFS Probability
Hide Description One-year PFS probability was defined as the probability (expressed as percentage) of PFS at 1 year after Cycle 1 Day 1.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started the treatment of Cycle 1.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of PFS
57.5
(35.3 to 74.5)
32.Secondary Outcome
Title Trough Plasma Concentration of Letrozole
Hide Description Plasma samples were analyzed for letrozole concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric (HPLC/MS/MS) method.
Time Frame pre-dose of Cycle 1 Days 19, 20, 21 and Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
"Number of Participants Analyzed" represents all enrolled and treated participants who had letrozole concentration data. "Number Analyzed" represents the number of such participants who had data at each specified time point.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 25
Median (Full Range)
Unit of Measure: nanograms per milliliter (ng/mL)
Cycle 1 Day 19 pre-dose Number Analyzed 23 participants
83.70
(30.8 to 134)
Cycle 1 Day 20 pre-dose Number Analyzed 24 participants
83.85
(41.4 to 141)
Cycle 1 Day 21 pre-dose Number Analyzed 24 participants
85.30
(38.2 to 134)
Cycle 2 Day 1 pre-dose Number Analyzed 25 participants
97.40
(48.8 to 282)
33.Secondary Outcome
Title Ratio Over Baseline for Skin Biomarker Phosphorylated Retinoblastoma Protein (pRb) Expression
Hide Description The pRb was one of the skin biomarkers and samples were assayed using immunohistochemistry (IHC) method. Ratio over baseline was calculated by dividing the H-score value for pRb at each specified time point by baseline value. The H-score value, which could range from 0 to 300 (strongest expression) with higher score representing stronger expression, was calculated from the total of each individual intensity of staining (0 [negative], 1+ [weak], 2+ [moderate], 3+ [strong]) multiplied by the percentages of cells (0 to 100) that represented that staining.
Time Frame Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
Lead-in phase Day 1 Number Analyzed 12 participants
0.644
(56.34%)
Lead-in phase Day 2 Number Analyzed 11 participants
0.523
(92.28%)
Cycle 1 Day 21 Number Analyzed 9 participants
0.535
(108.77%)
Cycle 1 Day 22 Number Analyzed 11 participants
0.773
(57.77%)
Cycle 1 Day 23 Number Analyzed 8 participants
0.799
(91.59%)
Cycle 1 Day 24 Number Analyzed 12 participants
1.493
(103.46%)
Cycle 1 Day 25 Number Analyzed 9 participants
1.165
(99.39%)
Cycle 1 Day 26 Number Analyzed 12 participants
2.164
(87.80%)
34.Secondary Outcome
Title Ratio Over Baseline for Skin Biomarker Ki67 Expression
Hide Description The Ki67 was one of the skin biomarkers and samples were assayed using IHC method. Ratio over baseline was calculated by dividing the percentage of Ki67 positive cells at each specified time point by baseline value.
Time Frame Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
Lead-in phase Day 1 Number Analyzed 12 participants
0.985
(42.32%)
Lead-in phase Day 2 Number Analyzed 11 participants
0.868
(64.99%)
Cycle 1 Day 21 Number Analyzed 9 participants
0.495
(107.24%)
Cycle 1 Day 22 Number Analyzed 11 participants
0.408
(135.34%)
Cycle 1 Day 23 Number Analyzed 8 participants
0.599
(80.00%)
Cycle 1 Day 24 Number Analyzed 12 participants
0.832
(42.34%)
Cycle 1 Day 25 Number Analyzed 9 participants
0.920
(85.52%)
Cycle 1 Day 26 Number Analyzed 12 participants
1.301
(61.26%)
35.Secondary Outcome
Title Ratio Over Baseline for Thymidine Kinase (TK) Concentration
Hide Description Blood samples were collected to provide serum for the assessments of TK activity. The concentrations of TK were determined using enzyme-linked immunosorbent assay (ELISA) method. Ratio of serum TK concentration at each specified time point over baseline value was presented.
Time Frame Baseline (Day -1 pre-dose), lead-in phase Day 1 (4, 8, 10, 24, 72, 120 hours post dose), Cycle 1 Day 21 (4, 8, 10, 24, 72, 96, 120 hours post dose), Cycle 2 Day 1 pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description:
Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
Lead-in phase Day 1, 4 hours post dose Number Analyzed 26 participants
0.780
(44.69%)
Lead-in phase Day 1, 8 hours post dose Number Analyzed 26 participants
0.774
(43.65%)
Lead-in phase Day 1, 10 hours post dose Number Analyzed 26 participants
0.733
(49.67%)
Lead-in phase Day 1, 24 hours post dose Number Analyzed 26 participants
0.702
(48.93%)
Lead-in phase Day 1, 72 hours post dose Number Analyzed 26 participants
0.530
(50.14%)
Lead-in phase Day 1, 120 hours post dose Number Analyzed 26 participants
0.598
(74.40%)
Cycle 1 Day 21, 4 hours post dose Number Analyzed 23 participants
0.260
(172.41%)
Cycle 1 Day 21, 8 hours post dose Number Analyzed 23 participants
0.236
(191.22%)
Cycle 1 Day 21, 10 hours post dose Number Analyzed 23 participants
0.236
(187.02%)
Cycle 1 Day 21, 24 hours post dose Number Analyzed 24 participants
0.247
(164.37%)
Cycle 1 Day 21, 48 hours post dose Number Analyzed 24 participants
0.244
(166.61%)
Cycle 1 Day 21, 72 hours post dose Number Analyzed 24 participants
0.268
(163.67%)
Cycle 1 Day 21, 96 hours post dose Number Analyzed 24 participants
0.292
(176.92%)
Cycle 1 Day 21, 120 hours post dose Number Analyzed 24 participants
0.455
(334.32%)
Cycle 2 Day 1, pre-dose Number Analyzed 24 participants
1.069
(248.43%)
Time Frame From first dose of study treatment up to 28 days after last dose (up to 2.8 years by primary completion date of 31 July 2018)
Adverse Event Reporting Description The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title Palbociclib + Letrozole
Hide Arm/Group Description Participants received palbociclib 125 milligrams (mg) orally once daily (QD) on Day 1 during the 5-day lead-in phase and from Day 1 to Day 21 (followed by 7 days off-treatment) during each treatment cycle. A treatment cycle was defined as 28 days in duration and Cycle 1 was started with Day 6 of lead-in phase as Cycle 1 Day 1. Letrozole 2.5 mg was administered orally QD from Days 1 to 5 during the 5-day lead-in phase and from Days 1 to 28 during each 28-day treatment cycle.
All-Cause Mortality
Palbociclib + Letrozole
Affected / at Risk (%)
Total   0/26 (0.00%) 
Hide Serious Adverse Events
Palbociclib + Letrozole
Affected / at Risk (%)
Total   2/26 (7.69%) 
Hepatobiliary disorders   
Drug-induced liver injury * 1  1/26 (3.85%) 
Infections and infestations   
Pneumonia * 1  1/26 (3.85%) 
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palbociclib + Letrozole
Affected / at Risk (%)
Total   26/26 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  12/26 (46.15%) 
Leukopenia * 1  10/26 (38.46%) 
Neutropenia * 1  10/26 (38.46%) 
Thrombocytopenia * 1  2/26 (7.69%) 
Eye disorders   
Lenticular opacities * 1  3/26 (11.54%) 
Gastrointestinal disorders   
Abdominal discomfort * 1  3/26 (11.54%) 
Diarrhoea * 1  2/26 (7.69%) 
Gingival pain * 1  2/26 (7.69%) 
Gingival ulceration * 1  4/26 (15.38%) 
Mouth ulceration * 1  3/26 (11.54%) 
Toothache * 1  3/26 (11.54%) 
General disorders   
Fatigue * 1  5/26 (19.23%) 
Pyrexia * 1  5/26 (19.23%) 
Infections and infestations   
Nasopharyngitis * 1  5/26 (19.23%) 
Upper respiratory tract infection * 1  3/26 (11.54%) 
Investigations   
Alanine aminotransferase increased * 1  7/26 (26.92%) 
Aspartate aminotransferase increased * 1  9/26 (34.62%) 
Blood alkaline phosphatase increased * 1  3/26 (11.54%) 
Blood cholesterol increased * 1  2/26 (7.69%) 
Blood creatinine increased * 1  2/26 (7.69%) 
Blood glucose increased * 1  3/26 (11.54%) 
Blood insulin increased * 1  2/26 (7.69%) 
Blood triglycerides increased * 1  3/26 (11.54%) 
Gamma-glutamyltransferase increased * 1  3/26 (11.54%) 
Haemoglobin decreased * 1  6/26 (23.08%) 
Low density lipoprotein increased * 1  2/26 (7.69%) 
Neutrophil count decreased * 1  16/26 (61.54%) 
Platelet count decreased * 1  14/26 (53.85%) 
Red blood cell count decreased * 1  3/26 (11.54%) 
Weight decreased * 1  2/26 (7.69%) 
Weight increased * 1  3/26 (11.54%) 
White blood cell count decreased * 1  15/26 (57.69%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  3/26 (11.54%) 
Diabetes mellitus * 1  2/26 (7.69%) 
Hypercholesterolaemia * 1  4/26 (15.38%) 
Hyperglycaemia * 1  3/26 (11.54%) 
Hyperlipidaemia * 1  2/26 (7.69%) 
Hypertriglyceridaemia * 1  2/26 (7.69%) 
Hyperuricaemia * 1  4/26 (15.38%) 
Hypocalcaemia * 1  4/26 (15.38%) 
Hypokalaemia * 1  4/26 (15.38%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  3/26 (11.54%) 
Bone pain * 1  2/26 (7.69%) 
Joint stiffness * 1  3/26 (11.54%) 
Musculoskeletal pain * 1  2/26 (7.69%) 
Nervous system disorders   
Dizziness * 1  3/26 (11.54%) 
Psychiatric disorders   
Insomnia * 1  4/26 (15.38%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  2/26 (7.69%) 
Haemoptysis * 1  2/26 (7.69%) 
Pneumonitis * 1  2/26 (7.69%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  2/26 (7.69%) 
Pruritus * 1  2/26 (7.69%) 
Rash * 1  3/26 (11.54%) 
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
The reported results were based on the data cut off at primary completion date (31 July 2018). The study is still ongoing and results will be updated after completion of the whole study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02499146    
Other Study ID Numbers: A5481019
First Submitted: July 13, 2015
First Posted: July 15, 2015
Results First Submitted: May 28, 2019
Results First Posted: July 29, 2019
Last Update Posted: July 29, 2019