Trial Outcomes & Findings for Pharmacokinetics And Dialysability Of CP-690,550 In Subjects With End-Stage Renal Disease (NCT NCT01710020)

NCT ID: NCT01710020

Last Updated: 2012-12-18

Results Overview

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 - ∞).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hours (hrs) post-dose in Period 1
• Results posted on: 2012-12-18

Participant Flow

Participant milestones

Measure	CP-690,550 (10 mg OPC) Single oral dose of CP-690,550 10 milligram (mg) oral powder for constitution (OPC) 1 to 2 hours (hrs) post-hemodialysis in Period 1 followed by single oral dose of CP-690,550 10 mg OPC approximately 4 hours prior to hemodialysis in Period 2. A washout period of at least 14 days was maintained between each intervention period.
Period 1 STARTED	12
Period 1 COMPLETED	11
Period 1 NOT COMPLETED	1
Washout Period (at Least 14 Days) STARTED	11
Washout Period (at Least 14 Days) COMPLETED	11
Washout Period (at Least 14 Days) NOT COMPLETED	0
Period 2 STARTED	11
Period 2 COMPLETED	11
Period 2 NOT COMPLETED	0

Reasons for withdrawal

Measure	CP-690,550 (10 mg OPC) Single oral dose of CP-690,550 10 milligram (mg) oral powder for constitution (OPC) 1 to 2 hours (hrs) post-hemodialysis in Period 1 followed by single oral dose of CP-690,550 10 mg OPC approximately 4 hours prior to hemodialysis in Period 2. A washout period of at least 14 days was maintained between each intervention period.
Period 1 Protocol Violation	1

Baseline Characteristics

Pharmacokinetics And Dialysability Of CP-690,550 In Subjects With End-Stage Renal Disease

Baseline characteristics by cohort

Measure	Entire Study Population n=12 Participants Includes all participants enrolled in the study.
Age Continuous	45.9 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hours (hrs) post-dose in Period 1

Population: Analysis set included all participants who received study medication.

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 - ∞).

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	396 nanogram*hour/milliliter (ng*hr/mL) Standard Deviation 158

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1

Population: Analysis set included all participants who received study medication.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	385 ng*hr/mL Standard Deviation 151

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1

Population: Analysis set included all participants who received study medication.

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Maximum Observed Plasma Concentration (Cmax)	106 nanogram/milliliter (ng/mL) Standard Deviation 23.9

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1

Population: Analysis set included all participants who received study medication.

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.5 hr Interval 0.5 to 0.5

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1

Population: Analysis set included all participants who received study medication.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Plasma Decay Half-Life (t1/2)	3.46 hr Standard Deviation 1.18

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1

Population: Analysis set included all participants who received study medication.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing given dose of drug with AUC.

Outcome measures

Measure	CP-690,550 (Period 1) n=12 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Oral Clearance (CLpo)	501 milliliter/minute (mL/min) Standard Deviation 243

PRIMARY outcome

Timeframe: 0 to 1 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided (/) by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=11 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Dialyser Clearance (CL HD) From 0 to 1 Hour	311 mL/min Standard Deviation 124

PRIMARY outcome

Timeframe: 1 to 2 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=11 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Dialyser Clearance (CL HD) From 1 to 2 Hour	325 mL/min Standard Deviation 138

PRIMARY outcome

Timeframe: 2 to 3 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=10 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Dialyser Clearance (CL HD) From 2 to 3 Hour	332 mL/min Standard Deviation 135

PRIMARY outcome

Timeframe: 3 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=7 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Dialyser Clearance (CL HD) From 3 to 4 Hour	292 mL/min Standard Deviation 111

SECONDARY outcome

Timeframe: 2 hours post-dose in Period 1

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.

Outcome measures

Measure	CP-690,550 (Period 1) n=11 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Fraction of Unbound Drug (fu)	0.390 ratio Standard Deviation 0.042

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=11 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Overall Dialyser Clearance (CL HD)	318 mL/min Standard Deviation 132

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 to 3.5 hrs during hemodialysis started 4 hrs post-dose in Period 2

Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu*Cmid*tm).

Outcome measures

Measure	CP-690,550 (Period 1) n=2 Participants Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.
Dialyser Clearance (CL HD) From 3 to 3.5 Hour	377 mL/min Standard Deviation 200

Adverse Events

CP-690,550 (Period 1)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

CP-690,550 (Period 2)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	CP-690,550 (Period 1) n=12 participants at risk Single oral dose of CP-690,550 10 mg OPC 1 to 2 hours post-hemodialysis in Period 1.	CP-690,550 (Period 2) n=11 participants at risk Single oral dose of CP-690,550 10 mg OPC approximately 4 hours prior to hemodialysis in Period 2.
General disorders Headache	16.7% 2/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Ecchymosis	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycemia	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Paresthesia	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough increased	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER