A Study Of CP-690,550 In Stable Kidney Transplant Patients
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01710033
Collaborator
(none)
28
11
4
19
2.5
0.1
Study Details
Study Description
Brief Summary
This was a Phase 1 dose escalation study to evaluate the safety, tolerability and pharmacokinetics of 28-day treatment of CP-690,550 in stable renal allograft recipients. In Stage 1, ascending doses of CP-690,550 were to be administered sequentially to 3-4 cohorts of subjects. After Stage 1, one dose level was to be selected for dosing in an expanded cohort in Stage 2.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
28 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
Phase 1, Placebo-controlled, Randomized, Sequential, Parallel-group, Dose Escalation Study to Evaluate 28-day Multiple Dose Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CP-690,550 in Stable Renal Allograft Recipients
Study Start Date
:
Sep 1, 2003
Actual Primary Completion Date
:
Apr 1, 2005
Actual Study Completion Date
:
Apr 1, 2005
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: Placebo
Placebo tables twice daily (BID) for 28 days
|
| Experimental: CP-690,550 5 mg BID
|
Drug: CP-690,550 5 mg BID
CP-690,550 5 mg BID for 28 days
|
| Experimental: CP-690,550 15 mg BID
|
Drug: CP-690,550 15 mg BID
CP-690,550 15 mg BID for 28 days
|
| Experimental: CP-690,550 30 mg BID
|
Drug: CP-690,550 30 mg BID
CP-690,550 30 mg BID for 28 days
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) at Steady State For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state.
- Area Under the Curve From Time Zero to 12 Hour Concentration [AUC(0-12)] at Steady State For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 29]
Area under the plasma concentration time-curve from zero to 12 hour concentration [AUC(0-12)] at steady state.
- Maximum Observed Plasma Concentration (Cmax) For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1]
- Maximum Observed Plasma Concentration (Cmax) at Steady State For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29]
- Accumulation Ratio (Rac) For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 and 29]
Rac obtained from AUC(0-12) (Day 29) divided by AUC(0-12) (Day 1).
- Plasma Decay Half-Life (t1/2) For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Plasma Decay Half-Life (t1/2) at Steady State For CP-690,550 [0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half at steady state.
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline [Screening, 0 hour (pre-dose) on Day 1]
Pro-drug MMF was metabolically converted to active form MPA in the liver. The baseline for MPA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 8 [0 hour (pre-dose) on Day 8]
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 15 [0 hour (pre-dose) on Day 15]
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 29 [0 hour (pre-dose) on Day 29]
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
- Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 57 [0 hour (pre-dose) on Day 57]
Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.
- Cyclosporine (CsA) Plasma Trough Concentration at Baseline [Screening, 0 hour (pre-dose) on Day 1]
The baseline for CsA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
- Cyclosporine (CsA) Plasma Trough Concentration at Day 8 [0 hour (pre-dose) on Day 8]
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
- Cyclosporine (CsA) Plasma Trough Concentration at Day 15 [0 hour (pre-dose) on Day 15]
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
- Cyclosporine (CsA) Plasma Trough Concentration at Day 29 [0 hour (pre-dose) on Day 29]
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
- Cyclosporine (CsA) Plasma Trough Concentration at Day 57 [0 hour (pre-dose) on Day 57]
CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.
- Tacrolimus (TAC) Plasma Trough Concentration at Baseline [Screening, 0 hour (pre-dose) on Day 1]
The baseline for TAC trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
- Tacrolimus (TAC) Plasma Trough Concentration at Day 8 [0 hour (pre-dose) on Day 8]
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
- Tacrolimus (TAC) Plasma Trough Concentration at Day 15 [0 hour (pre-dose) on Day 15]
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
- Tacrolimus (TAC) Plasma Trough Concentration at Day 29 [0 hour (pre-dose) on Day 29]
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
- Tacrolimus (TAC) Plasma Trough Concentration at Day 57 [0 hour (pre-dose) on Day 57]
TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Medically stable kidney transplant patients 6 or more months after transplantation.
-
Subjects must be on mycophenolate mofetil 1-2 gm daily
-
In Cohort 3 (and 4, if conducted) in Stage 1 and the expanded cohort in Stage 2, subjects must be on a calcineurin inhibitor-free regimen.
Exclusion Criteria:
-
Any rejection episodes in the preceding 3 months.
-
Treated with Thymoglobulin or OKT3 for acute rejection in the past 6 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35249-6860 |
| 2 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35249 |
| 3 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35294-6862 |
| 4 | Pfizer Investigational Site | Los Angeles | California | United States | 90057 |
| 5 | Pfizer Investigational Site | Indianapolis | Indiana | United States | 46202 |
| 6 | Pfizer Investigational Site | Minneapolis | Minnesota | United States | 55404 |
| 7 | Pfizer Investigational Site | St Louis | Missouri | United States | 63110-1093 |
| 8 | Pfizer Investigational Site | St. Louis | Missouri | United States | 63110-1092 |
| 9 | Pfizer Investigational Site | Livingston | New Jersey | United States | 07039 |
| 10 | Pfizer Investigational Site | Madison | Wisconsin | United States | 53792 |
| 11 | Pfizer Investigational Site |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01710033
Other Study ID Numbers:
- A3921007
First Posted:
Oct 18, 2012
Last Update Posted:
Dec 26, 2012
Last Verified:
Nov 1, 2012
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 | CP-690,550 30 mg, Stage 2 |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (mycophenolate mofetil [MMF] with or without calcineurin inhibitor [cyclosporine {CsA} or tacrolimus {TAC}]) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 2. |
| Period Title: Stage 1 | |||||
| STARTED | 6 | 6 | 6 | 6 | 0 |
| COMPLETED | 6 | 6 | 6 | 6 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
| Period Title: Stage 1 | |||||
| STARTED | 0 | 0 | 0 | 0 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 10 | 28 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
54.5
(15.0)
|
53.0
(15.5)
|
46.0
(17.8)
|
54.2
(14.3)
|
52.3
(15.0)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
1
16.7%
|
3
50%
|
2
20%
|
8
28.6%
|
| Male |
4
66.7%
|
5
83.3%
|
3
50%
|
8
80%
|
20
71.4%
|
Outcome Measures
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For CP-690,550 |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 8 |
| Mean (Standard Deviation) [nanogram*hour per milliliter (ng*hr/mL)] |
183
(75.3)
|
754
(182)
|
1200
(266)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) at Steady State For CP-690,550 |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state. |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 9 |
| Mean (Standard Deviation) [ng*hr/mL] |
319
(175)
|
1300
(241)
|
1560
(311)
|
| Title | Area Under the Curve From Time Zero to 12 Hour Concentration [AUC(0-12)] at Steady State For CP-690,550 |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to 12 hour concentration [AUC(0-12)] at steady state. |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 5 | 9 |
| Mean (Standard Deviation) [ng*hr/mL] |
273
(132)
|
1090
(150)
|
1420
(253)
|
| Title | Maximum Observed Plasma Concentration (Cmax) For CP-690,550 |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 8 |
| Mean (Standard Deviation) [nanogram per milliliter (ng/mL)] |
41.0
(14.9)
|
140
(34.5)
|
325
(113)
|
| Title | Maximum Observed Plasma Concentration (Cmax) at Steady State For CP-690,550 |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 5 | 9 |
| Mean (Standard Deviation) [ng/mL] |
52.2
(15.2)
|
220
(39.4)
|
351
(46.3)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) For CP-690,550 |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 8 |
| Median (Full Range) [hours] |
0.75
|
1.50
|
0.50
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State For CP-690,550 |
|---|---|
| Description | |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 5 | 9 |
| Median (Full Range) [hours] |
0.75
|
0.50
|
0.50
|
| Title | Accumulation Ratio (Rac) For CP-690,550 |
|---|---|
| Description | Rac obtained from AUC(0-12) (Day 29) divided by AUC(0-12) (Day 1). |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 5 | 7 |
| Mean (Standard Deviation) [ratio] |
1.48
(0.467)
|
1.39
(0.245)
|
1.22
(0.182)
|
| Title | Plasma Decay Half-Life (t1/2) For CP-690,550 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12 hours post-dose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 4 | 2 | 8 |
| Mean (Standard Deviation) [hours] |
3.36
(0.869)
|
NA
(NA)
|
2.94
(0.620)
|
| Title | Plasma Decay Half-Life (t1/2) at Steady State For CP-690,550 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half at steady state. |
| Time Frame | 0 (pre-dose), 0.5, 1, 2, 4, 8, 10, 12, 24 hours post-dose on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|
| Arm/Group Description | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 4 | 8 |
| Mean (Standard Deviation) [hours] |
5.18
(2.00)
|
5.15
(1.12)
|
3.71
(0.201)
|
| Title | Mycophenolic Acid (MPA) Plasma Trough Concentration at Baseline |
|---|---|
| Description | Pro-drug MMF was metabolically converted to active form MPA in the liver. The baseline for MPA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure. |
| Time Frame | Screening, 0 hour (pre-dose) on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 10 |
| Mean (Standard Deviation) [Milligram per Liter (mg/L)] |
2.73
(1.23)
|
2.18
(1.80)
|
1.84
(1.13)
|
2.43
(1.80)
|
| Title | Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 8 |
|---|---|
| Description | Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 10 |
| Mean (Standard Deviation) [mg/L] |
3.25
(2.77)
|
2.11
(2.01)
|
1.29
(0.48)
|
2.56
(1.62)
|
| Title | Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 15 |
|---|---|
| Description | Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 10 |
| Mean (Standard Deviation) [mg/L] |
3.15
(1.75)
|
2.36
(2.21)
|
1.48
(0.63)
|
2.74
(1.52)
|
| Title | Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 29 |
|---|---|
| Description | Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 10 |
| Mean (Standard Deviation) [mg/L] |
2.61
(1.77)
|
2.68
(2.00)
|
4.30
(3.88)
|
3.24
(1.71)
|
| Title | Mycophenolic Acid (MPA) Plasma Trough Concentration at Day 57 |
|---|---|
| Description | Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. |
| Measure Participants | 6 | 5 | 6 | 10 |
| Mean (Standard Deviation) [mg/L] |
2.60
(1.56)
|
2.89
(2.75)
|
1.75
(1.10)
|
2.67
(1.87)
|
| Title | Cyclosporine (CsA) Plasma Trough Concentration at Baseline |
|---|---|
| Description | The baseline for CsA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. |
| Time Frame | Screening, 0 hour (pre-dose) on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 1 | 5 | 3 |
| Mean (Standard Deviation) [ng/mL] |
249.50
(NA)
|
81.00
(41.99)
|
173.00
(51.11)
|
| Title | Cyclosporine (CsA) Plasma Trough Concentration at Day 8 |
|---|---|
| Description | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 1 | 4 | 3 |
| Mean (Standard Deviation) [ng/mL] |
137.00
(NA)
|
77.25
(47.28)
|
134.00
(17.78)
|
| Title | Cyclosporine (CsA) Plasma Trough Concentration at Day 15 |
|---|---|
| Description | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 1 | 5 | 3 |
| Mean (Standard Deviation) [ng/mL] |
207.00
(NA)
|
86.60
(43.71)
|
160.33
(24.58)
|
| Title | Cyclosporine (CsA) Plasma Trough Concentration at Day 29 |
|---|---|
| Description | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 1 | 5 | 3 |
| Mean (Standard Deviation) [ng/mL] |
226.00
(NA)
|
96.00
(53.43)
|
125.00
(22.34)
|
| Title | Cyclosporine (CsA) Plasma Trough Concentration at Day 57 |
|---|---|
| Description | CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 1 | 5 | 3 |
| Mean (Standard Deviation) [ng/mL] |
292.00
(NA)
|
91.20
(72.71)
|
152.00
(43.28)
|
| Title | Tacrolimus (TAC) Plasma Trough Concentration at Baseline |
|---|---|
| Description | The baseline for TAC trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. |
| Time Frame | Screening, 0 hour (pre-dose) on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 2 | 3 |
| Mean (Standard Deviation) [ng/mL] |
6.75
(2.47)
|
7.17
(1.76)
|
| Title | Tacrolimus (TAC) Plasma Trough Concentration at Day 8 |
|---|---|
| Description | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 2 | 3 |
| Mean (Standard Deviation) [ng/mL] |
7.50
(2.12)
|
8.00
(1.00)
|
| Title | Tacrolimus (TAC) Plasma Trough Concentration at Day 15 |
|---|---|
| Description | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 2 | 3 |
| Mean (Standard Deviation) [ng/mL] |
8.00
(2.83)
|
6.67
(2.08)
|
| Title | Tacrolimus (TAC) Plasma Trough Concentration at Day 29 |
|---|---|
| Description | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 2 | 3 |
| Mean (Standard Deviation) [ng/mL] |
7.00
(2.83)
|
12.67
(4.51)
|
| Title | Tacrolimus (TAC) Plasma Trough Concentration at Day 57 |
|---|---|
| Description | TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure. |
| Time Frame | 0 hour (pre-dose) on Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all randomized participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 15 mg, Stage 1 |
|---|---|---|
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. |
| Measure Participants | 2 | 3 |
| Mean (Standard Deviation) [ng/mL] |
5.00
(1.41)
|
6.33
(0.58)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 | ||||
| Arm/Group Description | Placebo matched to CP-690,550 tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) with or without calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 5 milligram (mg) tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA) as per local clinical practice in Stage 1. | CP-690,550 15 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF), calcineurin inhibitor (CsA or TAC) as per local clinical practice in Stage 1. | CP-690,550 30 mg tablet orally twice daily up to Day 28 followed by single oral dose on Day 29 in stable renal transplant recipients, receiving maintenance immunosuppression therapy (MMF) as per local clinical practice in Stage 1 and 2. | ||||
All Cause Mortality |
||||||||
| Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 1/10 (10%) | ||||
| Infections and infestations | ||||||||
| Gastroenteritis | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/10 (0%) | ||||
| Urinary tract infection | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Viral infection | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Investigations | ||||||||
| Blood creatinine increased | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo, Stage 1 | CP-690,550 5 mg, Stage 1 | CP-690,550 15 mg, Stage 1 | CP-690,550 30 mg, Stage 1 And 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/6 (83.3%) | 5/6 (83.3%) | 5/6 (83.3%) | 8/10 (80%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 1/10 (10%) | ||||
| Leukocytosis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/10 (20%) | ||||
| Eye disorders | ||||||||
| Conjunctival haemorrhage | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/10 (0%) | ||||
| Abdominal pain lower | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Diarrhoea | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Dyspepsia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/10 (20%) | ||||
| Eructation | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Gastrooesophageal reflux disease | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Gingival hyperplasia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Vomiting | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| General disorders | ||||||||
| Catheter site haemorrhage | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Fatigue | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Malaise | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/10 (0%) | ||||
| Cytomegalovirus viraemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Gastroenteritis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Herpes simplex | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/10 (20%) | ||||
| Laryngitis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Nasopharyngitis | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Onychomycosis | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Pharyngitis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Pneumonia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Sinusitis | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Tinea versicolour | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Tonsillitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Upper respiratory tract infection | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Urinary tract infection | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Viral infection | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Viral upper respiratory tract infection | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
| Investigations | ||||||||
| Liver function test abnormal | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Reticulocyte count decreased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Hypokalaemia | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Increased appetite | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Back pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Chest wall pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Neck pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/10 (10%) | ||||
| Pain in extremity | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 1/6 (16.7%) | 3/6 (50%) | 0/6 (0%) | 1/10 (10%) | ||||
| Psychiatric disorders | ||||||||
| Abnormal dreams | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Anxiety | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Insomnia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Sleep disorder | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/10 (10%) | ||||
| Nasal congestion | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | ||||
| Pharyngolaryngeal pain | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01710033
Other Study ID Numbers:
- A3921007
First Posted:
Oct 18, 2012
Last Update Posted:
Dec 26, 2012
Last Verified:
Nov 1, 2012