A Renal Impairment Study for PF-06651600

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04037865
• Collaborator: (none)
• Enrollment: 8
• Locations: 3
• Arms: 4
• Actual Duration (Months): 7.4
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase 1 non-randomized, open-label, parallel cohort study of PF-06651600 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with mild and moderate renal impairment (Part 2).

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: PF-06651600	Phase 1

Detailed Description

This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06651600 after multiple oral doses of 50 mg daily. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately 16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 11 will be a maximum of 39 days and from Screening visit to Follow-up/Contact Visit will a maximum of 73 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN PARTICIPANTS WITH RENAL IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL RENAL FUNCTION
• Actual Study Start Date: Aug 19, 2019
• Actual Primary Completion Date: Mar 31, 2020
• Actual Study Completion Date: Mar 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-06651600 Severe Renal Impairment This arm includes participants with severe renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Normal Renal Function This arm includes participants with normal renal function who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Moderate Renal Impairment This arm is in Part 2 which will be conducted if decision criterion to proceed to Part 2 is met. This arm includes participants with moderate renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Mild Renal Impairment This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10.	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10

Outcome Measures

Primary Outcome Measures

1. Plasma PF-06651600 Maximum Plasma Concentration (Cmax) [On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11.]

   The plasma PF-06651600 Cmax was observed directly from data.

2. Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) [On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11.]

   Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method.

Secondary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.]

   An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is considered a TEAE is the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. An AE was considered treatment-related if the causality of the AE was assessed to be the investigational product. The causality of AEs was assessed by the investigator using clinical judgment.

2. Number of Participants With Laboratory Abnormalities [At Screening Visit 1 and on Days -1, 5, 11 and early termination day.]

   Safety laboratory assessments include clinical chemistry, hematology and urinalysis. Serum creatinine was only assessed on Screening visit 2 and on Day 2 and Day 8 for eGFR assessment. The number of participants with laboratory test abnormalities without regard to baseline abnormality was reported.

3. Number of Participants With Vital Signs Data Meeting Pre-specified Criteria [At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation.]

   Vital signs evaluations included supine blood pressure (BP), pulse rate, and temperature. Criteria for vital signs values included: supine diastolic BP >= 20 mmHg increase from baseline, supine systolic BP >= 30 mmHg increase from baseline, supine diastolic BP >= 20 mmHg decrease from baseline, and supine systolic BP >= 30 mmHg decrease from baseline.

4. Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria [At screening, on Day -1, Day 11 and early termination/discontinuation.]

   ECG criteria included PR, QT, and QTc intervals and QRS complex. Participants with absolute data value meeting the following criteria were reported: aggregate PR interval value >= 300 msec, aggregate QRS duration value >= 140 msec, absolute QTcF interval value >450 msec and <= 480 msec, or >480 msec and <=500 msec, or >500 msec.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body mass index (BMI) of >/= 17.5 to </= 40.0 kg/m2; and a total body weight > 50 kg (110 lb)

Additional inclusion criteria for subjects with renal impairment:

• Meet the following eGFR criteria during the screening period based upon MDRD equation:

• Severe renal impairment: eGFR <30 mL/min but not requiring hemodialysis

• Moderate renal impairment (Part 2 only): eGFR >/=30 mL/min and <60 mL/min

• Mild renal impairment (Part 2 only): eGFR between 60 and 89 mL/min

• Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included)

• Stable drug regimen

Exclusion Criteria:

• Females of child-bearing potential must use an accepted, highly effective contraceptive method

• Renal transplant recipients

• Urinary incontinence without catheterization

• Subjects with clinically significant infections within the past 6 months prior to first dose of study drug, evidence of active or chronic infection requiring oral treatment within 4 weeks prior, history of disseminated herpes simplex or recurrent or disseminated herpes zoster

• Subjects with malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of skin or cervical carcinoma in situ

• HIV, Hepatitis B, or Hepatitis C infection

Additional exclusion criteria for subjects with renal impairment:

• Subjects requiring hemodialysis and peritoneal dialysis

• Screening BP >/=180 mmHg (systolic) or >/=110 mmHg (diastolic)

• Screening 12-lead ECG demonstrating QTcF >470 msec

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Drug Services (IDS) University of Miami Hospitals and Clinics	Miami	Florida	United States	33136
2	University of Miami Division of Clinical Pharmacology	Miami	Florida	United States	33136
3	Prism Clinical Research, LLC	Saint Paul	Minnesota	United States	55114

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

• Study Protocol - May 10, 2019
• Statistical Analysis Plan - Jul 1, 2019

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04037865
• Other Study ID Numbers: B7981020
• First Posted: Jul 30, 2019
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Renal Insufficiency

Study Results

Participant Flow

Recruitment Details	The study was terminated, only participants with severe renal impairment were enrolled. Therefore, in this study, data were collected only for participants with severe renal impairment.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Overall Participants	8
Age (Years) [Mean (Standard Deviation) ]
Mean	59.5 (9.78)
Age, Customized (Count of Participants)
<18 Years	0 0%
18-44 Years	1 12.5%
45-64 Years	4 50%
>=65 Years	3 37.5%
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%
Race/Ethnicity, Customized (Count of Participants)
White	7 87.5%
Black or African American	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Plasma PF-06651600 Maximum Plasma Concentration (Cmax)
Description	The plasma PF-06651600 Cmax was observed directly from data.
Time Frame	On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	445.6 (21)

2. Primary Outcome

Title	Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)
Description	Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method.
Time Frame	On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]	986.3 (33)

3. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is considered a TEAE is the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. An AE was considered treatment-related if the causality of the AE was assessed to be the investigational product. The causality of AEs was assessed by the investigator using clinical judgment.
Time Frame	From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
All-causality TEAEs	3 37.5%
Treatment-related TEAEs	2 25%

4. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	Safety laboratory assessments include clinical chemistry, hematology and urinalysis. Serum creatinine was only assessed on Screening visit 2 and on Day 2 and Day 8 for eGFR assessment. The number of participants with laboratory test abnormalities without regard to baseline abnormality was reported.
Time Frame	At Screening Visit 1 and on Days -1, 5, 11 and early termination day.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
Erythrocytes <0.8xlower limit of normal (LLN)	1 12.5%
Erythrocytes mean corpuscular hemoglobin >1.8*upper limit of normal (ULN)	1 12.5%
Lymphocytes/leukocytes <0.8*LLN	2 25%
Eosinophils/leukocytes >1.2*ULN	1 12.5%
Blood urea nitrogen >1.3*ULN	8 100%
Creatine >1.3*ULN	8 100%
Urate >1.2*ULN	6 75%
Bicarbonate <0.9*ULN	1 12.5%
Glucose >1.5*ULN	1 12.5%
Urine glucose >=1	2 25%
Urine protein >=1	6 75%
Urine hemoglobin >=1	3 37.5%
Leukocyte esterase >=1	2 25%

5. Secondary Outcome

Title	Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Description	Vital signs evaluations included supine blood pressure (BP), pulse rate, and temperature. Criteria for vital signs values included: supine diastolic BP >= 20 mmHg increase from baseline, supine systolic BP >= 30 mmHg increase from baseline, supine diastolic BP >= 20 mmHg decrease from baseline, and supine systolic BP >= 30 mmHg decrease from baseline.
Time Frame	At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
Count of Participants [Participants]	1 12.5%

6. Secondary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria
Description	ECG criteria included PR, QT, and QTc intervals and QRS complex. Participants with absolute data value meeting the following criteria were reported: aggregate PR interval value >= 300 msec, aggregate QRS duration value >= 140 msec, absolute QTcF interval value >450 msec and <= 480 msec, or >480 msec and <=500 msec, or >500 msec.
Time Frame	At screening, on Day -1, Day 11 and early termination/discontinuation.

Outcome Measure Data

Analysis Population Description

The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

Arm/Group Title	Severe Renal Impairment
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.
Measure Participants	8
QRS duration value >= 140 msec	1 12.5%
QTcF interval value >450 msec and <=480 msec	1 12.5%

Adverse Events

Time Frame	From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.
Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were recorded on the CRF. SAEs were also reported on the Clinical Trial (CT) SAE report form to Pfizer Safety within 24 hours of awareness.
Arm/Group Title	Severe Renal Impairment		Total
Arm/Group Description	Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease.		All participants.
All Cause Mortality
	Severe Renal Impairment		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Severe Renal Impairment		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Severe Renal Impairment		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		3/8 (37.5%)
Eye disorders
Dry eye	1/8 (12.5%)		1/8 (12.5%)
Investigations
Alanine aminotransferase increased	1/8 (12.5%)		1/8 (12.5%)
Aspartate aminotransferase increased	1/8 (12.5%)		1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/8 (12.5%)		1/8 (12.5%)
Nervous system disorders
Dizziness	1/8 (12.5%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/8 (12.5%)		1/8 (12.5%)

Limitations/Caveats

Since the study was terminated, the results of this study was not complete and the interpretation of the study results was limited.

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.